Clinical and Molecular Hepatology

Current consensus and guidelines of contrast enhanced ultrasound for the characterization of ...

Mon, 25 Mar 2013 00:00:01 +0100

The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data.

Hepatitis C virus: virology and life cycle

Chang Wook Kim and Kyong-Mi Chang — Mon, 25 Mar 2013 00:00:01 +0100

Hepatitis C virus (HCV) is a positive sense, single-stranded RNA virus in the Flaviviridae family. It causes acute hepatitis with a high propensity for chronic infection. Chronic HCV infection can progress to severe liver disease including cirrhosis and hepatocellular carcinoma. In the last decade, our basic understanding of HCV virology and life cycle has advanced greatly with the development of HCV cell culture and replication systems. Our ability to treat HCV infection has also been improved with the combined use of interferon, ribavirin and small molecule inhibitors of the virally encoded NS3/4A protease, although better therapeutic options are needed with greater antiviral efficacy and less toxicity. In this article, we review various aspects of HCV life cycle including viral attachment, entry, fusion, viral RNA translation, posttranslational processing, HCV replication, viral assembly and release. Each of these steps provides potential targets for novel antiviral therapeutics to cure HCV infection and prevent the adverse consequences of progressive liver disease.

Is peginterferon and ribavirin therapy effective in Korean patients with chronic hepatitis C?

Young Kul Jung and Ju Hyun Kim — Mon, 25 Mar 2013 00:00:01 +0100

Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic ...

Mon, 25 Mar 2013 00:00:01 +0100

Background/Aims: The incidence of multidrug-resistant (MDR) chronic hepatitis B (CHB) during sequential lamivudine (LAM) and adefovir dipivoxil (ADV) treatment is increasing. We investigated the antiviral efficacies of various rescue regimens in patients who failed sequential LAM-ADV treatment.
Methods: Forty-eight patients (83.3% of whom were HBeAg-positive) who failed sequential LAM-ADV treatment were treated with one of the following regimens: entecavir (ETV) (1 mg) monotherapy (n=16), LAM+ADV combination therapy (n=20), or ETV (1 mg)+ADV combination therapy (n=12). All patients had confirmed genotypic resistance to both LAM and ADV and were evaluated every 12 weeks.
Results: The baseline characteristics and treatment duration did not differ significantly among the study groups. During the treatment period (median duration: 100 weeks), the decline of serum HBV DNA from baseline tended to be greatest in the ETV+ADV group at all-time points (week 48: -2.55 log₁₀ IU/mL, week 96: -4.27 log₁₀ IU/mL), but the difference was not statistically significant. The ETV+ADV group also tended to have higher virologic response rates at 96 weeks compared to the ETV monotherapy or LAM+ADV groups (40.0% vs. 20.0% or 20.0%, P=0.656), and less virologic breakthrough was observed compared to the ETV monotherapy or LAM+ADV groups (8.3% vs. 37.5% or 30.0%; P =0.219), but again, the differences were not statistically significant. HBeAg loss occurred in one patient in the ETV+ADV group, in two in the ETV monotherapy group, and in none of the LAM+ADV group. The safety profiles were similar in each arm.
Conclusions: There was a nonsignificant tendency toward better antiviral efficacy with ETV+ADV combination therapy compared to LAM+ADV combination therapy and ETV monotherapy for MDR CHB in Korea, where tenofovir is not yet available.

Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data

Mon, 25 Mar 2013 00:00:01 +0100

Background/Aims: While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea.
Methods: The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated.
Results: The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001).
Conclusions: The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis.

Clinical and epidemiological characteristics of Korean patients with hepatitis C virus genotype 6

Mon, 25 Mar 2013 00:00:01 +0100

Background/Aims: The distribution of hepatitis C virus (HCV) genotypes varies geographically. In Korea, genotypes 1 and 2 comprise more than 90% of HCV infections, while genotype 6 is very rare. This study compared the clinical and epidemiological characteristics of patients with genotype 6 HCV infection with those infected with HCV genotypes 1 and 2.
Methods: This was a prospective, multicenter HCV cohort study that enrolled 1,173 adult patients, of which 930 underwent HCV genotype analysis, and only 9 (1.0%) were found to be infected with genotype 6 HCV. The clinical and epidemiological parameters of the genotypes were compared.
Results: The patients with genotype 6 HCV had a mean age of 41.5 years, 77.8% were male, and they had no distinct laboratory features. A sustained virologic response (SVR) was observed in four (67%) of six patients who received antiviral therapy. Risk factors such as the presence of a tattoo (n=6, 66.7%), more than three sexual partners (n=3, 33.3%), and injection drug use (n=3, 33.3%) were more common among genotype 6 patients than among genotypes 1 or 2.
Conclusions: The epidemiology and treatment response of patients infected with genotype 6 HCV differed significantly from those with genotypes 1 or 2, warranting continuous monitoring.

A study of hepatitis B virus reactivation associated with rituximab therapy in real-world ...

Myung Jin Oh and Heon Ju Lee — Mon, 25 Mar 2013 00:00:01 +0100

Background/Aims: The widespread use of cytotoxic chemotherapy and immunosuppressants has resulted in reactivation of hepatitis B virus (HBV) recently becoming an issue. Although rituximab (an anti-CD20 monoclonal antibody) has revolutionized the treatment of lymphoma, recent reports have suggested that rituximab therapy increases the risk of viral-mediated complications, and particularly HBV reactivation. This study analyzed real clinical practice data for rituximab-related HBV reactivation.
Methods: Between January 2005 and December 2011, 169 patients received treatment with rituximab. Screening status of the HBV infection and frequency of preemptive therapy were determined in these patients, and the clinical features of HBV reactivation were analyzed.
Results: Seventy-nine of the 169 patients with chronic or past HBV infection were selected for evaluation of HBV reactivation. Of the 90 patients who were excluded, 22 (13.0%) were not assessed for HBsAg and anti-HBc, and 14 (8.3%) were not assessed for anti-HBc due to seronegativity for HBsAg. The selected patients were divided into those with chronic HBV infection (n=12) and those with past HBV infection (n=67); six patients (7.6%) experienced HBV reactivation. Eight patients received preemptive therapy, but three patients (37.5%) underwent HBV reactivation. Although HBsAg seropositivity was an independent risk factor for HBV reactivation (P=0.038), of the six patients with HBV reactivation, two (33.3%) had past HBV infection and three (50%) died of liver failure.
Conclusions: The findings of this study demonstrate that adherence to guidelines for screening and preemptive therapy for HBV reactivation was negligent among the included cohort. Attention should be paid to HBV reactivation in patients with past as well as chronic HBV infection during and after rituximab therapy.

High effectiveness of peginterferon alfa-2a plus ribavirin therapy in Korean patients with ...

Mon, 25 Mar 2013 00:00:01 +0100

Background/Aims: Identifying the impact of a patient’s ethnicity on treatment responses in clinical practice may assist in providing individualized treatment regimens for chronic hepatitis C (CHC). The effectiveness of standard peginterferon plus ribavirin therapy and the need for triple combination therapy with protease inhibitors in Koreans remain matters of debate. These issues were investigated in the present study.
Methods: The clinical data of 272 treatment-naïve Korean CHC patients who were treated in a community-based clinical trial (Clinical Trial group; n=51) and in clinical practice (Cohort group; n=221), were analyzed and compared. All were treated with standard protocols of peginterferon alfa-2a plus ribavirin therapy.
Results: For patients with hepatitis C virus (HCV) genotype 1, the sustained virological response (SVR) rates in the Clinical Trial and Cohort groups were 81% (21/26) and 55% (58/106), respectively, by intention-to-treat (ITT) analysis (P=0.02), and 100% (13/13) and 80% (32/40), respectively, in treatment-adherent patients (P=0.18). For patients with HCV genotype 2, the SVR rates in these two groups were 96% (24/25) and 88% (101/115), respectively, by ITT analysis (P=0.31). Adherence and treatment duration were independent predictors of SVR for genotypes 1 and 2, respectively (P<0.01 for each). Korean patients with CHC achieved high SVR rates with peginterferon alfa-2a plus ribavirin in both the clinical trial and clinical practice settings.
Conclusions: Measures to raise adherence to standard therapy in clinical practice may improve the SVR rates in these patients as effectively as adding protease inhibitors, thus obviating the need for the latter.

Impact of serum C-reactive protein level on the prognosis of patients with hepatocellular ...

Mon, 25 Mar 2013 00:00:01 +0100

Background/Aims: The aim of this study was to determine the relationship between serum CRP levels and the prognosis of hepatocellular carcinoma (HCC) patients.
Methods: HCC patients who underwent the first session of transcatheter arterial chemoembolization (TACE) between January 2005 and December 2009 (n=211) were analyzed retrospectively. The patients were divided into two groups: high C-reactive protein (CRP; ≥1 mg/dL, n=51) and low CRP (<1 mg/dL, n=160). They were followed for a mean of 22.44 months and their clinicoradiological variables and overall survival were compared.
Results: There were significant differences between the two groups in regard to tumor type, tumor-progression-free survival, 10-month mortality, white blood cell (WBC) count, tumor size, and TNM stage. Multivariate analysis revealed that a high serum CRP level was independently associated with tumor size and tumor type. Subgroup analysis of CRP groups according to tumor size demonstrated that a high serum level of CRP was significantly associated with poorly defined (diffuse) tumor type in the tumor size <5 cm group [hazard ratio (HR)=4.81, P=0.018]. A Lipiodol dose exceeding 7 mL (HR=5.55, P=0.046) and the 10-month mortality (HR=7.693, P=0.004) were significantly associated with high serum CRP level in the group of patients with a tumor size of ≥5 cm. In addition, subgroup analysis of matched CRP according to TNM stage revealed that elevated serum CRP was independently associated with tumor type, WBC count, and tumorprogression- free survival.
Conclusions: A high serum CRP level is associated with large tumors and a poorly defined tumor type, and is significantly associated with 10-month mortality in patients with large HCC (size ≥5 cm) who undergo TACE.

A case of variceal bleeding from the jejunum in liver cirrhosis

Mon, 25 Mar 2013 00:00:01 +0100

While esophagogastric varices are common manifestations of portal hypertension, variceal bleeding from the jejunum is a rare complication of liver cirrhosis. In addition, ectopic variceal bleeding occurs in the duodenum and at sites of previous bowel surgery in most cases, including of stomas. We report a case of obscure overt gastrointestinal bleeding from jejunal varices in a 55-year-old woman who had not previously undergone abdominal surgery, who had liver cirrhosis induced by the hepatitis C virus. Emergency endoscopy revealed the presence of esophageal varices without stigmata of recent bleeding, and no bleeding focus was found at colonoscopy. She continued to produce recurrent melena with hematochezia and received up to 21 units of packed red blood cells. CT angiography revealed the presence of jejunal varices, but no active bleeding was found. Capsule endoscopy revealed fresh blood in the jejunum. The patient submitted to embolization of the jejunal varices via the portal vein, after which she had a stable hemoglobin level and no recurrence of the melena. This is a case of variceal bleeding from the jejunum in a liver cirrhosis patient without a prior history of abdominal surgery.

Two cases of telbivudine-induced myopathy in siblings with chronic hepatitis B

Mon, 25 Mar 2013 00:00:01 +0100

Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine has a more potent and sustained antiviral activity with a lower frequency of viral resistance than lamivudine. Although there are several reports concerning the safety profile of telbivudine, most adverse events are described as mild and transient in nature. Here we report two cases of telbivudine-induced myopathy in patients with chronic hepatitis B who were siblings.

Reactive lymphoid hyperplasia of the liver

Woo Sung Moon and Keum Ha Choi — Mon, 25 Mar 2013 00:00:01 +0100

Hepatocellular carcinoma composed of two different histologic types: imaging features on ...

Mon, 25 Mar 2013 00:00:01 +0100

Antitoxin treatment for liver abscess caused by Clostridium perfringens

Toru Hifumi, Yuichi Koido, Motohide Takahashi, and Akihiko Yamamoto — Mon, 25 Mar 2013 00:00:01 +0100

The role of gut-liver axis in the pathogenesis of liver cirrhosis and portal hypertension

Yeon Seok Seo and Vijay H. Shah — Mon, 24 Dec 2012 00:00:01 +0100

Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension.

Hepatitis C virus and hepatocarcinogenesis

Soung Won Jeong, Jae Young Jang, and Raymond T. Chung — Mon, 24 Dec 2012 00:00:01 +0100

Hepatitis C virus (HCV) is an RNA virus that is unable to integrate into the host genome. However, its proteins interact with various host proteins and induce host responses. The oncogenic process of HCV infection is slow and insidious and probably requires multiple steps of genetic and epigenetic alterations, the activation of cellular oncogenes, the inactivation of tumor suppressor genes, and dysregulation of multiple signal transduction pathways. Stellate cells may transdifferentiate into progenitor cells and possibly be linked to the development of hepatocellular carcinoma (HCC). Viral proteins also have been implicated in several cellular signal transduction pathways that affect cell survival, proliferation, migration and transformation. Current advances in gene expression profile and selective messenger RNA analysis have improved approach to the pathogenesis of HCC. The heterogeneity of genetic events observed in HCVrelated HCCs has suggested that complex mechanisms underlie malignant transformation induced by HCV infection. Considering the complexity and heterogeneity of HCCs of both etiological and genetic aspects, further molecular classification is required and an understanding of these molecular complexities may provide the opportunity for effective chemoprevention and personalized therapy for HCV-related HCC patients in the future. In this review, we summarize the current knowledge of the mechanisms of hepatocarcinogenesis induced by HCV infection.

Elevated serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease

Byoung Kuk Jang — Mon, 24 Dec 2012 00:00:01 +0100

Efficacy of peginterferon and ribavirin is associated with the IL28B gene in Korean patients ...

Mon, 24 Dec 2012 00:00:01 +0100

Background/Aims: Sustained virologic response (SVR) for the treatment of chronic hepatitis C (CHC) may differ with ethnicity due to differences in genetic traits. This study evaluated the efficacy of peginterferon and ribavirin, and the association between IL28B genotypes and the treatment efficacy in Korean CHC patients.
Methods: This was a retrospective cohort study using data from medical records. Eighty-five CHC patients were eligible for assessment of the efficacy of antiviral therapy, and 47 patients were available for an IL28B genetic study, which was performed using the Multiplex tetra-primer PCR method for rs12979860.
Results: Overall, the early virologic response rate was 87.1%: 84.9% in HCV genotype 1 and 90.6% in genotype 2. The overall end-of-treatment virologic response rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. The overall SVR rate was 81.2%: 75.5% in genotype 1 and 90.6% in genotype 2. For rs12979860, the frequencies of polymorphisms were 89% for the CC type, 11% for the CT type, and 0% for the TT type. Their overall SVR rate was 87% (39/47): 90.5% (38/42) for the CC type and 20% (1/5) for the CT type. For genotype 1, SVR rates were 88% (21/24) for the CC type and 0% (0/4) for the CT type. Multivariate analysis revealed that the IL28B-CC type was a good predictor for SVR.
Conclusions: The SVR of the combination therapy in Koreans was higher than that observed in Western countries. This finding might be attributable to the high prevalence of IL28B-CC type among Koreans, which may be a good predictor of SVR.

Clinical outcomes of balloon-occluded retrograde transvenous obliteration for the treatment ...

Mon, 24 Dec 2012 00:00:01 +0100

Background/Aims: This study evaluated the clinical outcomes of balloon-occluded retrograde transvenous obliteration (BRTO) for the treatment of hemorrhage from gastric varices (GV) in Korean patients with liver cirrhosis (LC).
Methods: We retrospectively analyzed data from 183 LC patients who underwent BRTO for GV bleeding in 6 universitybased hospitals between January 2001 and December 2010.
Results: Of the 183 enrolled patients, 49 patients had Child-Pugh (CP) class A LC, 105 had CP class B, and 30 had CP class C at the time of BRTO. BRTO was successfully performed in 177 patients (96.7%). Procedure-related complications (e.g., pulmonary thromboembolism and renal infarction) occurred in eight patients (4.4%). Among 151 patients who underwent follow-up examinations of GV, 79 patients (52.3%) achieved eradication of GV, and 110 patients (72.8%) exhibited marked shrinkage of the treated GV to grade 0 or I. Meanwhile, new-appearance or aggravation of esophageal varices (EV) occurred in 54 out of 136 patients who underwent follow-up endoscopy (41.2%). During the 36.0±29.2 months (mean±SD) of follow-up, 39 patients rebled (hemorrhage from GV in 7, EV in 18, nonvariceal origin in 4, and unknown in 10 patients). The estimated 3-year rebleeding-free rate was 74.8%, and multivariate analysis showed that CP class C was associated with rebleeding (odds ratio, 2.404; 95% confidence-interval, 1.013-5.704; P=0.047).
Conclusions: BRTO can be performed safely and effectively for the treatment of GV bleeding. However, aggravation of EV or bleeding from EV is not uncommon after BRTO; thus, periodic endoscopy to follow-up of EV with or without prophylactic treatment might be necessary in LC patients undergoing BRTO.

Prognostic indicators in primary biliary cirrhosis: significance of revised IAHG ...

Mon, 24 Dec 2012 00:00:01 +0100

Background/Aims: Primary biliary cirrhosis (PBC) is a slowly progressing autoimmune disease of the liver that is characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Serum total bilirubin is one of the various prognostic factors that have been proposed. A recent study found that PBC with accompanying autoimmune hepatitis (AIH) carries a negative prognosis. This study examined the clinical characteristics of PBC and analyzed the factors that affect its prognosis.
Methods: Patients diagnosed with PBC between January 1998 and December 2010 based on clinical and histopathological findings were compiled and analyzed retrospectively.
Results: Among 27 patients, 24 (1 male and 23 females, ages 50.0±9.3 years) were followed up. The follow-up period was 8.6±0.9 years. Of the 24 patients, 9 patients progressed to liver cirrhosis (LC). Comparison between patients who did and did not progress to LC revealed statistically significant differences in the patients’ serum total bilirubin (2.7±1.8 vs. 0.8±0.4, P =0.012), the Mayo risk score (5.1±0.7 vs. 3.9±0.6, P =0.001), the revised IAHG (International Autoimmune Hepatitis Group) score (9.2±2.3 vs. 5.4±3.0, P=0.004) and frequency of AIH overlap (5/9 [55.6%] vs. 0/15 [0%], P=0.001) at the time of diagnosis.
Conclusions: We propose that serum total bilirubin, the Mayo risk score, and the revised IAHG score at the time of diagnosis are helpful for predicting PBC prognosis. In particular, since all of the patients with accompanying AIH progressed to LC, the presence of overlap syndrome at the time of diagnosis is helpful for predicting PBC prognosis and providing an adequate treatment.

Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease

Mon, 24 Dec 2012 00:00:01 +0100

Background/Aims: Serum bilirubin exerts antioxidant and cytoprotective effects. In addition, elevated serum bilirubin levels are associated with a decreased risk of metabolic and cardiovascular diseases. However, few studies have evaluated whether serum bilirubin is associated with non-alcoholic fatty liver disease (NAFLD), which is closely associated with other metabolic diseases. The aim of this study was thus to elucidate the association between serum total bilirubin levels and NAFLD.
Methods: A cross-sectional study of 17,348 subjects undergoing a routine health check-up was conducted. Subjects positive for hepatitis B or hepatitis C virus, or with other hepatitis history were excluded. NAFLD was diagnosed on the basis of typical ultrasonographic findings and an alcohol consumption of less than 20 g/day.
Results: The mean age of the subjects was 49 years and 9,076 (52.3%) were men. The prevalence of NAFLD decreased steadily as the serum bilirubin level increased in both men and women (P<0.001 for both). Multivariate regression analysis adjusted for other metabolic risk factors showed that serum bilirubin level was inversely associated with the prevalence of NAFLD [odds ratio (OR)=0.88, 95% confidence interval (CI)=0.80-0.97]. Furthermore, there was an inverse, dose-dependent association between NAFLD and serum total bilirubin levels (OR=0.83, 95% CI=0.75-0.93 in the third quartile; OR=0.80, 95% CI=0.71-0.90 in the fourth quartile vs. lowest quartile, P for trend <0.001).
Conclusions: Serum bilirubin levels were found to be inversely associated with the prevalence of NAFLD independent of known metabolic risk factors. Serum bilirubin might be a protective marker for NAFLD.

Relationship between the hepatic venous pressure gradient and first variceal hemorrhage in ...

Mon, 24 Dec 2012 00:00:01 +0100

Background/Aims: Variceal hemorrhage is one of the major complications of cirrhosis and is associated with significant mortality and morbidity. The development of gastroesophageal varices and variceal hemorrhage is the most direct consequence of portal hypertension. Correlations between the hepatic venous pressure gradient (HVPG) and first variceal hemorrhage were examined.
Methods: Patients with cirrhosis who underwent HVPG measurement between July 2009 and September 2010 were enrolled (n=535). All patients underwent esophagogastroduodenoscopy to enable the evaluation of gastroesophageal varices.
Results: The HVPG for all patients was 16.46±7.05 mmHg (mean±SD), and was significantly higher among those with first variceal hemorrhage than in those without it. The HVPG was significantly correlated with both Child-Turcotte-Pugh (r=0.488, P<0.001) and Model for End-stage Liver Disease (r=0.478, P<0.001) scores. An HVPG value of 11 mmHg was predictive of first variceal hemorrhage with a sensitivity of 92.4% and a specificity of 27.7%.
Conclusions: The HVPG was higher in patients with first variceal hemorrhage than in those without it.

Multiplex polymerase chain reaction test for the diagnosis of acute viral hepatitis A

Nae-Yun Heo, Young-Suk Lim, Jihyun An, Sun-Young Ko, and Heung-Bum Oh — Mon, 24 Dec 2012 00:00:01 +0100

Background/Aims: The early diagnosis of acute hepatitis A (AHA) is hindered because serum IgM against hepatitis A virus (HAV) can yield false-negative results during the window period. This study evaluated the diagnostic accuracy of a polymerase chain reaction (PCR) kit for HAV RNA for the diagnosis of AHA.
Methods: Samples were collected from 136 patients with acute severe hepatitis at their admission to Asan Medical Center between June 2010 and July 2010. Samples were analyzed for serum IgM anti-HAV using an immunoassay test and for qualitative HAV RNA using the Magicplex HepaTrio PCR test kit. The diagnostic accuracies of these methods were tested on the basis of clinical and laboratory diagnoses of AHA.
Results: The concordance rate and kappa value between IgM anti-HAV and HAV RNA PCR were 88.2% and 0.707, respectively. For the diagnosis of AHA, the sensitivity and specificity of IgM anti-HAV were 90.7% and 100%, respectively, when an “equivocal” result was regarded as positive; and 79.1% and 100%, respectively, when an “equivocal” result was regarded as negative. The sensitivity and specificity of HAV RNA PCR were 81.4% and 100%, respectively. All four patients with negative IgM anti-HAV and positive HAV RNA PCR results and all four patients with equivocal IgM anti-HAV RNA and positive HAV RNA PCR results were eventually diagnosed with AHA.
Conclusions: The qualitative HAV RNA PCR test has an equivalent diagnostic accuracy for AHA compared to IgM anti- HAV and may be more sensitive during the window period.

Severe steatohepatitis with hepatic decompensation resulting from malnutrition after ...

Mon, 24 Dec 2012 00:00:01 +0100

The most common finding related to nonalcoholic steatohepatitis is obesity, but a status of severe malnutrition can also induce the steatohepatitis. The authors report a rare case of steatohepatitis leading to hepatic decompensation caused by malnutrition after pancreaticoduodenectomy. A 68-year-old female patient who had been previously diagnosed with pancreatic cancer and had undergone pancreaticoduodenectomy 5 months previously presented with abdominal distension. Routine CT performed 3 months after the surgery revealed severe fatty liver without evidence of tumor recurrence. After undergoing pancreaticoduodenectomy her food intake had reduced, and as a result she had lost 7 kg of body weight over 2 months. At this admission, CT revealed moderate amounts of ascites without tumor recurrence. Furthermore, her albumin and lipid profile levels were markedly decreased, and she had a flapping tremor and slurred speech suggestive of hepatic encephalopathy. Her liver biopsy findings were consistent with steatohepatitis and disclosed macrovesicular steatosis without definite fibrosis. After careful nutritional control, her symptoms disappeared and her laboratory findings improved.

Liver transplantation for acute-on-chronic liver failure from erythropoietic protoporphyria

Mon, 24 Dec 2012 00:00:01 +0100

Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway that is characterized by accumulation of protoporphyrin in the blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity, all resulting from abnormalities in ferrochelatase (FECH) activity due to mutations in the FECH gene. Protoporphyrin is excreted by the liver, and excess protoporphyrin leads to cholelithiasis with obstructive episodes and chronic liver disease, finally progressing to liver cirrhosis. Patients with end-stage EPP-associated liver disease require liver transplantation. We describe here a 31-year-old male patient with EPP who experienced acute-on-chronic liver failure and underwent deceased-donor liver transplantation. Surgical and postoperative care included specific shielding from exposure to ultraviolet radiation to prevent photosensitivity-associated adverse effects. The patient recovered uneventfully and was doing well 24 months after transplantation. Future prevention and treatment of liver disease are discussed in detail.

Exophytic combined hepatocellular carcinoma and cholangiocarcinoma

Sang Jae Noh, Hyun Kyung Lee, Hee Chul Yu, and Woo Sung Moon — Mon, 24 Dec 2012 00:00:01 +0100

Hepatic metastases from hepatoid adenocarcinoma of stomach mimicking hepatocellular carcinoma

Mon, 24 Dec 2012 00:00:01 +0100

Drug-induced liver injury: present and future

Ki Tae Suk, Dong Joon Kim — Wed, 26 Sep 2012 00:00:01 +0100

Liver injury due to prescription and nonprescription medications is a growing medical, scientific, and public health problem. Worldwide, the estimated annual incidence rate of drug-induced liver injury (DILI) is 13.9-24.0 per 100,000 inhabitants. DILI is one of the leading causes of acute liver failure in the US. In Korea, the annual extrapolated incidence of cases hospitalized at university hospital is 12/100,000 persons/year. Most cases of DILI are the result of idiosyncratic metabolic responses or unexpected reactions to medication. There is marked geographic variation in relevant agents; antibiotics, anticonvulsants, and psychotropic drugs are the most common offending agents in the West, whereas in Asia, ‘herbs’ and ‘health foods or dietary supplements’ are more common. Different medical circumstances also cause discrepancy in definition and classification of DILI between West and Asia. In the concern of causality assessment, the application of the Roussel Uclaf Causality Assessment Method (RUCAM) scale frequently undercounts the cases caused by ‘herbs’ due to a lack of previous information and incompatible time criteria. Therefore, a more objective and reproducible tool that could be used for the diagnosis of DILI caused by ‘herbs’ is needed in Asia. In addition, a reporting system similar to the Drug-Induced Liver Injury Network (DILIN) in the US should be established as soon as possible in Asia.

Changes of guidelines diagnosing hepatocellular carcinoma during the last ten-year period

Do Seon Song, Si Hyun Bae — Wed, 26 Sep 2012 00:00:01 +0100

Hepatocellular carcinoma (HCC) is the third most common cause of cancer deaths in the world. There have been many advances in the diagnosis of HCC during the last ten years, especially in the imaging techniques. The Korean Liver cancer study group (KLCSG), European Association for the Study of the Liver (EASL), American Association for the Study of Liver disease (AASLD), and Asian-Pacific Association for the Study of Liver (APASL) have made and changed the HCC guidelines with the advances in the imaging techniques and according to the results of the researches on HCC. We reviewed the changes of the imaging guidelines in HCC diagnosis according to the advances in the imaging techniques. Further studies will be necessary to resolve the controversies in the diagnosis of HCC smaller than 1 cm in size.

Impact of ribavirin dose reduction during treatment in chronic hepatitis C genotype 1 patients

Woo Jin Chung — Wed, 26 Sep 2012 00:00:01 +0100

A reduced dose of ribavirin does not influence the virologic response during pegylated ...

Wed, 26 Sep 2012 00:00:01 +0100

Background/Aims: When combined with pegylated interferon alpha-2b (Peg-IFN α-2b) for the treatment of genotype 1 chronic hepatitis C (CHC) in Korea, the current guideline for the initial ribavirin (RBV) dose is based on body weight. However, since the mean body weight is lower for Korean patients than for patients in Western countries, current guidelines might result in Korean patients being overdosed with RBV.
Methods: We retrospectively reviewed the medical records of patients with genotype 1 CHC who were treated with Peg- IFN α-2b and RBV combination therapy. We divided the patients into groups A (≥15 mg/kg/day, n =23) and B (<15 mg/kg/ day, n =26), given that the standard dose is 15 mg/kg/day. The clinical course in terms of the virologic response, adverse events, and dose modification rate was compared between the two groups after therapy completion.
Results: The early response rates (92.0% vs. 83.3%, P=0.634) and sustained virologic response rates (82.6% vs. 73.1%, p=0.506) did not differ significantly between the two groups. During the treatment period, the RBV dose reduction rate was significantly higher in group A than in group B (60.9% vs. 23.1%, p=0.01).
Conclusions: RBV dose reduction is performed frequently when patients are treated according to the current Korean guidelines. Given that lowering the RBV dose did not appear to decrease the virologic response during therapy, reducing RBV doses below the current Korean guideline may be effective for treatment, especially in low-weight patients.

Enhanced A-FABP expression in visceral fat: potential contributor to the progression of NASH

Wed, 26 Sep 2012 00:00:01 +0100

Background/Aims: Adipose tissue is an active endocrine organ that secretes various metabolically important substances including adipokines, which represent a link between insulin resistance and nonalcoholic steatohepatitis (NASH). The factors responsible for the progression from simple steatosis to steatohepatitis remain elusive, but adipokine imbalance may play a pivotal role. We evaluated the expressions of adipokines such as visfatin, adipocyte-fatty-acid-binding protein (A-FABP), and retinol-binding protein-4 (RBP-4) in serum and tissue. The aim was to discover whether these adipokines are potential predictors of NASH.
Methods: Polymerase chain reaction, quantification of mRNA, and Western blots encoding A-FABP, RBP-4, and visfatin were used to study tissue samples from the liver, and visceral and subcutaneous adipose tissue. The tissue samples were from biopsy specimens obtained from patients with proven NASH who were undergoing laparoscopic cholecystectomy due to gallbladder polyps.
Results: Patients were classified into two groups: NASH, n =10 and non-NASH, n =20 according to their nonalcoholic fatty liver disease Activity Score. Although serum A-FABP levels did not differ between the two groups, the expressions of A-FABP mRNA and protein in the visceral adipose tissue were significantly higher in NASH group than in non-NASH group (104.34 vs. 97.05, P<0.05, and 190.01 vs. 95.15, P<0.01, respectively). Furthermore, the A-FABP protein expression ratio between visceral adipose tissue and liver was higher in NASH group than in non-NASH group (4.38 vs. 1.64, P<0.05).
Conclusions: NASH patients had higher levels of A-FABP expression in their visceral fat compared to non-NASH patients. This differential A-FABP expression may predispose patients to the progressive form of NASH.

Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis, cirrhosis and ...

Wed, 26 Sep 2012 00:00:01 +0100

Background/Aims: Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) are up-regulated in hepatocellular carcinoma (HCC). To investigate the levels of COX-2 and VEGF expression in chronic hepatitis (CH), cirrhosis, and HCC. Methods: The immunohistochemical expressions of COX-2 and VEGF were evaluated in tissues from patients with CH (n=95), cirrhosis (n=38), low-grade HCC (LG-HCC; n=6), and high-grade HCC (HG-HCC; n=29). Results: The COX-2 expression scores in CH, cirrhosis, LG-HCC, and HG-HCC were 3.3±1.9 (mean±SD), 4.2±1.7, 5.5±1.0, and 3.4±2.4, respectively (CH vs. cirrhosis, P =0.016; CH vs. LG-HCC, P =0.008; LG-HCC vs. HG-HCC, p=0.004), and the corresponding VEGF expression scores were 0.9±0.8, 1.5±0.7, 1.8±0.9, and 1.6±1.1 (CH vs. cirrhosis, p<0.001; CH vs. LGHCC, P=0.011; LG-HCC vs. HG-HCC, P=0.075). Both factors were correlated with the fibrosis stage in CH and cirrhosis (COX-2: r=0.427, p<0.001; VEGF: r=0.491, p<0.001). There was a significant correlation between COX-2 and VEGF in all of the tissue samples (r=0.648, p<0.001), and between high COX-2 and VEGF expression scores and survival (COX-2: P=0.001; VEGF: p<0.001). Conclusions: The expressions of both COX-2 and VEGF are significantly higher in cirrhosis and LG-HCC than in CH. High COX-2 and high VEGF expressions are associated with a high survival rate.

Association between apolipoprotein E genotype, chronic liver disease, and hepatitis B virus

Wed, 26 Sep 2012 00:00:01 +0100

Background/Aims: Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies.
Methods: This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits.
Results: The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype.
Conclusions: The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.

Thrombocytopenia represents a risk for deterioration of liver function after radiofrequency ...

Wed, 26 Sep 2012 00:00:01 +0100

Background/Aims: We evaluated changes in liver function parameters and risk factors for the deterioration of liver function 12 months after percutaneous radiofrequency ablation (RFA) therapy in patients with hepatocellular carcinoma (HCC).
Methods: The subjects in this retrospective study comprised 102 patients with HCC who had undergone RFA therapy and exhibited no recurrence of HCC 12 months thereafter. Serial changes in serum total bilirubin and albumin, prothrombin time, and Child-Pugh score were evaluated before RFA and 3, 6, 9, and 12 months thereafter. Deterioration of liver function was defined when the Child-Pugh score increased by at least 2 at 12 months after RFA therapy. We determined the factors related to aggravation of liver function after RFA therapy.
Results: Liver function had deteriorated 12 months after RFA in 29 patients (28.4%). Serum albumin levels decreased significantly from before (3.7±0.1 g/dL, mean±SD) to 12 months after RFA therapy (3.3±0.1 g/dL, P =0.002). The Child-Pugh score increased significantly during the same time period (from 6.1±0.2 to 7.2±0.3, P<0.001). Pre-RFA thrombocytopenia (≤100,000/mm³) was revealed as a significant risk factor for the deterioration of liver function after RFA. However, no patients had episodes of bleeding as a complication of RFA.
Conclusions: Among the liver-function parameters, serum albumin level was markedly decreased in HCC patients over the course of 24 months after RFA therapy. A pre-RFA thrombocytopenia represents a major risk factor for the deterioration of liver function.

Type and cause of liver disease in Korea: single-center experience, 2005-2010

Wed, 26 Sep 2012 00:00:01 +0100

Background/Aims: The aim of this study was to describe the types and causes of liver disease in patients from a single community hospital in Korea between April 2005 and May 2010.
Methods: A cohort of patients who visited the liver clinic of the hospital during the aforementioned time period were consecutively enrolled (n =6,307). Consistent diagnostic criteria for each liver disease were set by a single, experienced hepatologist, and the diagnosis of all of the enrolled patients was confirmed by retrospective review of their medical records.
Results: Among the 6,307 patients, 528 (8.4%) were classified as acute hepatitis, 3,957 (62.7%) as chronic hepatitis, 767 (12.2%) as liver cirrhosis, 509 (8.1%) as primary liver cancer, and 546 (8.7%) as a benign liver mass or other diseases. The etiologies in the acute hepatitis group in decreasing order of prevalence were hepatitis A (44.3%), toxic hepatitis (32.4%), other hepatitis viruses (13.8%), and cryptogenic hepatitis (9.1%). In the chronic hepatitis group, 51.2% of cases were attributed to viral hepatitis, 33.3% to nonalcoholic fatty liver disease, and 13.0% to alcoholic liver disease (ALD). Of the cirrhoses, 73.4% were attributable to viral causes and 18.1% to alcohol. Of the hepatocellular carcinoma cases, 86.6% were attributed to viral hepatitis and 11.6% to ALD. Among the benign tumors, hemangioma comprised 52.2% and cystic liver disease comprised 33.7%.
Conclusions: Knowledge of the current status of the type and cause of liver disease in Korea may be valuable as a basis for evaluating changing trends in liver disease in that country.

Spinal cord injury after conducting transcatheter arterial chemoembolization for costal ...

Wed, 26 Sep 2012 00:00:01 +0100

Transcatheter arterial chemoembolization (TACE) has been used widely to treat patients with unresectable hepatocellular carcinoma. However, this method can induce various adverse events caused by necrosis of the tumor itself or damage to nontumor tissues. In particular, neurologic side effects such as cerebral infarction and paraplegia, although rare, may cause severe sequelae and permanent disability. Detailed information regarding the treatment process and prognosis associated with this procedure is not yet available. We experienced a case of paraplegia that occurred after conducting TACE through the intercostal artery to treat hepatocellular carcinoma that had metastasized to the rib. In this case, TACE was attempted to relieve severe bone pain, which had persisted even after palliative radiotherapy. A sudden impairment of sensory and motor functions after TACE developed in the trunk below the level of the sternum and in both lower extremities. The patient subsequently received steroid pulse therapy along with supportive care and continuous rehabilitation. At the time of discharge the patient had recovered sufficiently to enable him to walk by himself, although some paresthesia and spasticity remained.

A case of necrotizing pancreatitis subsequent to transcatheter arterial chemoembolization in a ...

Wed, 26 Sep 2012 00:00:01 +0100

Necrotizing pancreatitis is one of the rare complications of transcatheter arterial chemoembolization (TACE). Necrotizing pancreatitis after TACE may result from the development of ischemia caused by regurgitation of embolic materials into the vessels supplying the pancreas. We report a case of post-TACE necrotizing pancreatitis with abscess formation in a patient with hepatocellular carcinoma. The patient had suffered hepatic artery injury due to repetitive TACE; during his 25th TACE procedure he had submitted to selective catheterization of the feeding vessel from the dorsal pancreatic artery with a cytotoxic agent and Gelfoam particles. The patient complained of abdominal pain after the TACE procedure, and a CT scan led to a diagnosis of necrotizing pancreatitis with abscess formation. The pancreatic abscess progressed despite general management of the pancreatitis, including antibiotics. Percutaneous catheter drainage was performed, and the symptoms of the patient improved.

Adenosquamous carcinoma of the liver

Shin Young Park, Eun Jung Cha, Woo Sung Moon — Wed, 26 Sep 2012 00:00:01 +0100

Hepatic angiomyolipoma with minimal fat, mimicking hepatocellular carcinoma

Wed, 26 Sep 2012 00:00:01 +0100

KASL Clinical Practice Guidelines: Management of chronic hepatitis B

The Korean Association for the Study of the Liver (KASL)* — Wed, 20 Jun 2012 00:00:01 +0100

Clinical applications of transient elastography

Kyu Sik Jung and Seung Up Kim — Wed, 20 Jun 2012 00:00:01 +0100

Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantifi cation of liver fi brosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fi brosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan®) is a novel non-invasive method for assessment of liver fi brosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice. (Clin Mol Hepatol 2012;18:163-173)

Noninvasive diagnostic criteria for hepatocellular carcinoma

Han Chu Lee — Wed, 20 Jun 2012 00:00:01 +0100

A clinical predictor of varices and portal hypertensive gastropathy in patients with chronic ...

Wed, 20 Jun 2012 00:00:01 +0100

Background/Aims: The aim of this study was to identify the parameters that could noninvasively predict the presence of esophageal/gastric varices and portal hypertensive gastropathy (PHG) in patients with chronic liver disease (CLD), and to determine the accuracy of those parameters.
Methods: We retrospectively analyzed 232 patients with CLD who underwent both upper endoscopy and liver CT within an interval of 3 months. The multidimensional index (M-Index) for spleen volume was obtained from the multiplication of splenic length, width, and thickness, as measured by computer tomography.
Results: The multivariate analysis revealed that platelet, albumin, and M-Index were independently associated with the presence of varices and PHG. We combined three independent parameters, and developed a varices and portal hypertensive gastropathy (VAP) scoring system (=[platelet count (/mm³)×albumin (g/dL)]/[M-Index (cm³)]). The area under the receiver operating characteristic curve of the VAP score was 0.850 (95% confi dence interval, 0.801-0.899). The VAP cut-off value of 861 had a sensitivity of 85.3%, a positive likelihood ratio of 3.17, and a negative predictive value of 86.4%. For predicting high-risk lesions for bleeding, with a cut-off value of 861 the sensitivity was 92.0%, the positive likelihood ratio was 2.20, and the negative predictive value was 96.4%.
Conclusions: The VAP score can predict the presence of varices and PHG in patients with CLD and may increase the costbenefi t of screening endoscopy in the clinical practice setting. A prospective validation study is necessary in the future. (Clin Mol Hepatol 2012;18:178-184)

Comparison of usefulness of clinical diagnostic criteria for hepatocellular carcinoma in a ...

Wed, 20 Jun 2012 00:00:01 +0100

Background/Aims: We compared the accuracy and usefulness of clinical diagnostic criteria for hepatocellular carcinoma in a hepatitis B virus (HBV)-endemic area.
Methods: We reviewed the medical records of 355 patients who had undergone liver resection or biopsy at our institution between January 2008 and December 2009. These patients were reevaluated using four noninvasive diagnostic criteria for hepatocellular carcinoma proposed by the European Association for the Study of the Liver (EASL), the American Association for the Study of Liver Diseases (AASLD), the Korean Liver Cancer Study Group and the National Cancer Center (KLCSG/NCC), and National Comprehensive Cancer Network (NCCN) guidelines.
Results: The overall sensitivity was highest using the KLCSG/NCC criteria (79.8%), followed by the AASLD (51.5%), EASL (38.4%), and NCCN (10.1%; P<0.001) criteria, whereas the specificity (84.5-98.3%) and positive predictive value (96.2– 98.3%) were similar for all of the criteria. The KLCSG/NCC criteria had an acceptable false-positive rate and the highest sensitivity among all of the patients, including those positive for HBsAg, those without liver cancer, and those with a tumor of at least 2 cm.
Conclusions: The KLCSG/NCC and AASLD criteria exhibited the highest sensitivity, and all four guidelines had a high specifi city among all of the patients. Based on the sensitivity and false-positive rate, the KLCSG/NCC criteria was the most useful in the majority of patients. Inclusion of HBV infection in the clinical diagnostic criteria for hepatocellular carcinoma would be reasonable and may lead to an improvement in the sensitivity, with acceptable false-positive rates, in HBVendemic areas. (Clin Mol Hepatol 2012;18:185-194)

Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in ...

Wed, 20 Jun 2012 00:00:01 +0100

Background/Aims: The aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV) therapy in chronic hepatitis B (CHB) patients.
Methods: The medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI) values and Alcohol Use Disorders Identifi cation Test (AUDIT) scores were obtained at 6 months after the initiation of ETV (0.5 mg daily) treatment.
Results: A BMI of 25 kg/m² or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3%) were obese and 17 (19.3%) were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT) normalization, and hepatitis B virus (HBV)-DNA negativity (<300 copies/mL) at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not diff er signifi cantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was signifi cantly lower among hazardous alcohol users (91.5% vs. 70.6%; P =0.033).
Conclusions: Obesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was signifi cantly lower among the hazardous alcohol users. (Clin Mol Hepatol 2012;18:195-202)

Is there any vindication for low dose nonselective

Wed, 20 Jun 2012 00:00:01 +0100

Background/Aims: Nonselective β-blockers (NSBBs), such as propranolol, reportedly exert a pleiotropic eff ect in liver cirrhosis. A previous report suggested that survival was higher in patients receiving adjusted doses of NSBBs than in ligation patients. This study investigated whether low-dose NSBB medication has benefi cial eff ects in patients with liver cirrhosis, especially in terms of overall survival.
Methods: We retrospectively studied 273 cirrhotic patients (199 males; age 53.6±10.2 years, mean±SD) who visited our institution between March 2003 and December 2007; follow-up data were collected until June 2011. Among them, 138 patients were given a low-dose NSBB (BB group: propranolol, 20-60 mg/day), and the remaining 135 patients were not given an NSBB (NBB group). Both groups were stratifi ed randomly according to Child-Turcotte-Pugh (CTP) classifi cation and age.
Results: The causes of liver cirrhosis were alcohol (n=109, 39.9%), hepatitis B virus (n=125, 45.8%), hepatitis C virus (n=20, 7.3%), and cryptogenic (n=19, 7.0%). The CTP classes were distributed as follows: A, n=116, 42.5%; B, n=126, 46.2%; and C, n=31, 11.4%. Neither the overall survival (P=0.133) nor the hepatocellular carcinoma (HCC)-free survival (P =0.910) diff ered signifi cantly between the BB and NBB groups [probability of overall survival at 4 years: 75.1% (95% CI=67.7-82.5%) and 81.2% (95% CI=74.4–88.0%), respectively; P=0.236]. In addition, the delta CTP score did not diff er signifi cantly between the two groups.
Conclusions: Use of low-dose NSBB medication in patients with liver cirrhosis is not indicated in terms of overall and HCC-free survival. (Clin Mol Hepatol 2012;18:203-212)

The clinical features of drug-induced liver injury observed through liver biopsy: focus on ...

Wed, 20 Jun 2012 00:00:01 +0100

Background/Aims: Accurate diagnosis of drug-induced liver injury (DILI) is diffi cult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH.
Methods: The clinical, serologic, and histologic fi ndings of 29 patients were compared and analyzed. The patients were aged 46.2±12.8 years (mean±SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively.
Results: Aspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase levels were 662.2±574.8 U/L, 905.4±794.9 U/L, 12.9±10.8 mg/dL, 195.8±123.3 U/L, and 255.3±280.8 U/L, respectively. According to serologic and histologic fi ndings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited signifi cantly higher AST levels (537.1±519.1 vs. 1043.3±600.5 U/L), globulin levels (2.7±0.4 vs. 3.3±0.5 g/dL), and prothrombin time (12.9±2.4 vs. 15.2±3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplifi ed AIH score was 3.7±0.9 in the DILI group and 6.5±0.9 in the AIH group (P<0.001).
Conclusions: Accurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered. (Clin Mol Hepatol 2012;18:213-218)

Hepatitis C virus (HCV) genotypes and the influence of HCV subtype 1b on the progression of ...

Wed, 20 Jun 2012 00:00:01 +0100

Background/Aims: The re is some controversy regarding whether or not hepatitis C virus (HCV) subtype 1b is more infl uential than non-1b subtypes on the progression of chronic hepatitis (CH) C to liver cirrhosis (LC) and hepatocellular carcinoma (HCC).
Methods: We retrospectively analyzed 823 patients with chronic HCV infection, including 443 CH patients, 264 LC patients, and 116 HCC patients, who were HCV RNA positive and HBsAg negative. These patients had not received any prior treatment with either interferon alone or a combination of interferon and ribavirin.
Results: HCV subtypes 1b (51.6%) and 2a/2c (39.5%) were the two most common genotypes. The proportions of genotypes 2 (2a/2c, 2b, and 2) and 3 were 45.8% and 1.1%, respectively. One case of genotype 4 was found. HCV subtype 1b (47.3%) was less common than the non-1b subtypes (52.7%) in non-LC patients, but its proportion (56.9%) was higher than that of non-1b subtypes (43.1%) in LC patients (P=0.006). The proportions of patients with HCV subtype 1b did not diff er signifi cantly between the LC (55.3%) and HCC (60.3%) groups. Older age, male gender, and the relative progression of liver damage (non-LC vs. compensated LC vs. decompensated LC) were significant risk factors for HCC, with odds ratios of 1.081 (95% confi dence interval [CI], 1.056-1.106), 5.749 (95% CI, 3.329-9.930), and 2.895 (95% CI, 2.183-3.840), respectively. HCV subtype 1b was not a signifi cant risk factor for HCC (odds ratio, 1.423; 95% CI, 0.895-2.262).
Conclusions: HCV subtypes 1b and 2a/2c were the two most common HCV genotypes. HCV subtype 1b seemed to be more infl uential than non-1b subtypes on the progression of CH to LC, but not on the development of HCC from LC. (Clin Mol Hepatol 2012;18:219-224)

A fatal case of hepatitis B virus (HBV) reactivation during long-term, very-low-dose steroid ...

Wed, 20 Jun 2012 00:00:01 +0100

Hepatitis B virus (HBV) may be reactivated after chemotherapy or immunosuppressive therapy, and therefore administration of antiviral agents before such treatment is recommended. Most reported cases of reactivation are associated with high doses of immunosuppressive agents or combination therapy. We present a case of a previously inactive HBV carrier with an acute severe flare-up during a long-term, very-low-dose (2.5 mg/day) steroid treatment for rheumatoid arthritis. We suggest that even a minimal dose of single-regimen oral steroid can cause reactivation of indolent, inactive HBV. (Clin Mol Hepatol 2012;18:225-228)

Concurrent hepatic adenomatoid tumor and hepatic hemangioma: a case report

Wed, 20 Jun 2012 00:00:01 +0100

A 45-year-old male with alleged asymptomatic hepatic hemangioma of 4 years duration had right upper-quadrant pain and was referred to a tertiary hospital. Computed tomography and magnetic resonance imaging scans revealed a hypervascular mass of about 7 cm containing intratumoral multilobulated cysts. A preoperative liver biopsy was performed, but this failed to provide a defi nitive diagnosis. The patient underwent a partial hepatectomy of segments IV and VIII. The histologic fi ndings revealed multifocal proliferation of fl attened or cuboidal epithelioid cells and a highly vascular edematous stroma. Immunohistochemistry fi ndings demonstrated that the epithelioid tumor cells were positive for cytokeratin (AE1/AE3), vimentin, calretinin, and cytokeratin 5/6, and were focally positive for CD10, and negative for WT1 and CD34, all of which support their mesothelial origin. Immunohistochemistry for a mesothelial marker should be performed for determining the presence of an adenomatoid tumor when benign epithelioid cells are seen. (Clin Mol Hepatol 2012;18:229-234)

Solitary necrotic nodule of the liver

Sang Jae Noh, Sarangerel Jachin, and Woo Sung Moon — Wed, 20 Jun 2012 00:00:01 +0100

Hepatic inflammatory pseudotumor misinterpreted as hepatocellular carcinoma

Wed, 20 Jun 2012 00:00:01 +0100

Noninvasive diagnosis of hepatocellular carcinoma

Byung Seok Kim — Wed, 20 Jun 2012 00:00:01 +0100

Revision and update on clinical practice guideline for liver cirrhosis

Fri, 23 Mar 2012 00:00:01 +0100

Recent trends in the treatment of chronic hepatitis C

Dae Won Jun, Won Young Tak, Si Hyun Bae, and Youn Jae Lee — Fri, 23 Mar 2012 00:00:01 +0100

Pegylated interferon and ribavirin combination therapy is accepted as the standard antiviral treatment for chronic hepatitis C regardless of HCV genotype. This combination therapy achieves higher response rates than previous therapy, but, nevertheless, a large proportion of patients suffer from treatment failure or adverse events. Recent clinical studies of viral kinetics during antiviral treatment have led to the introduction of response-guided therapy, the concept of ‘customized therapy depending on viral response’, which focuses on modulation of the treatment period depending on the viral response to create a sustained viral response without unnecessary medication and costs. New upcoming direct-acting antivirals (DAAs) maximize response rate, and triple therapy including DAAs along with pegylated interferon and ribavirin combination therapy could soon be the standard therapy. In this article, we reviewed the factors affecting treatment, response guided treatment, retreatment after failure of standard treatment, management of adverse events during treatment, and new treatment options.

The effect of alanine aminotransferase dynamics on predicting sustained virological ...

Tae Yeob Kim — Fri, 23 Mar 2012 00:00:01 +0100

See Article on Page 41

Efficacy and safety of metronomic chemotherapy for patients with advanced primary ...

Fri, 23 Mar 2012 00:00:01 +0100

Background/Aims: Low-dose metronomic chemotherapy involves the frequent administration of comparatively low doses of cytotoxic agents with no extended breaks, and it may be as efficient as and less toxic than the conventional maximum tolerated dose therapy. This study evaluated the feasibility and therapeutic efficacy of metronomic chemotherapy in patients with advanced hepatocellular carcinoma (HCC) with major portal vein thrombosis (PVT). Methods: Thirty consecutive HCC patients with major PVT with or without extrahepatic metastasis were prospectively allocated to metronomic chemotherapy consisting of epirubicin being infused through the correct hepatic artery at a dose of 30 mg/body surface area (BSA) every 4 weeks, and cisplatin (15 mg/BSA) and 5-fluorouracil (50 mg/BSA) every week for 3 weeks, with intervening 1 week breaks. The treatment response was assessed using response evaluation criteria in solid tumors (RECIST). Results: In total, 116 cycles of metronomic chemotherapy were administered to the 30 patients, with a median of 3 cycles given to individual patients (range, 1-15 cycles). Six patients (20.0%) achieved a partial response and six patients (20.0%) had stable disease. The median time to disease progression and overall survival were 63 days (range, 26-631 days) and 162 days (95% confidence interval; range, 62-262 days), respectively. Overall survival was significantly associated with baseline alpha-fetoprotein level (P=0.001) and tumor response (P=0.005). The baseline alpha-fetoprotein level was significantly associated with the disease control rate (P=0.007). Adverse events were tolerable and managed successfully with conservative treatment. Conclusions: Metronomic chemotherapy may be a safe and useful palliative treatment in HCC patients with major PVT.

Rapid normalization of alanine aminotransferase predicts viral response during combined ...

Fri, 23 Mar 2012 00:00:01 +0100

Background/Aims: The treatment for chronic hepatitis C (CHC) is removal of the virus in order to prevent progression to liver cirrhosis and hepatocellular carcinoma (HCC). Few data have been presented regarding the clinical significance of changes in the alanine aminotransferase (ALT) level in this context. We analyzed the patterns of changes in ALT level and investigated the relationship between the rapid normalization of ALT and sustained virologic response (SVR) after combined treatment with peginterferon and ribavirin. Methods: CHC patients (n=370) were classified into four groups according to the initial ALT level and subsequent changes: (1) initially abnormal ALT level and sustained abnormal ALT level during treatment, (2) initially abnormal ALT level but achievement of ALT normalization, (3) initially normal ALT level and variable ALT abnormality during treatment, and (4) initially normal ALT level and sustained normalization of ALT level during treatment. We subdivided groups 1 and 2 into those with patterns of decreased and normalization of ALT, with or without rapid normalization. We checked the end-treatment response (ETR) and SVR rates in each group and the factors associated with SVR, including patterns of changes in ALT level. Results: A total of 168 patients completed the therapy (age=54.34±10.64 years [mean±SD], 95 males [56.5%], genotype 1:82 [48.8%]). SVR was achieved in 115 (68.45%) of the completely treated patients. The SVR rate was significantly lower in group 1 than in group 2 (37.8 vs. 81.6%, P<0.001), and significantly higher in the rapid normalization group than in the group without rapid normalization (78.5% vs. 41.2%, P<0.001). Multiple logistic regression analysis revealed that age (odds ratio [OR]=0.94, 95% confidence interval [CI]=0.91-0.98, P=0.005), viral genotype (OR=2.76, 95% CI=1.20-6.38, P=0.017), and initial hepatitis C virus RNA titer (OR=0.28, 95% CI=0.10-0.75, P=0.012) were identified as independent significant predictive factors for SVR. Conclusions: The SVR rate is significantly associated with normalization, and especially rapid normalization of ALT. Rapid normalization of ALT by 4 weeks after treatment might be a useful response factor that is readily available in clinical practice, and especially for genotype 1 patients.

Analysis of prognostic factors and 5-year survival rate in patients with hepatocellular ...

Fri, 23 Mar 2012 00:00:01 +0100

Background/Aims: Hepatocellular carcinoma (HCC), which is the third most common cancer in Korea, has a very poor prognosis. However, only a few studies have performed a comprehensive survival-related analysis in all patients who were consecutively diagnosed and treated over a given period of time. The aim of this study was to determine the 5-year survival rate and its prognostic factors among HCC patients. Methods: In total, 257 patients who were consecutively diagnosed with HCC between January 2000 and December 2003 were followed until death or until December 2008. We analyzed their survival outcomes according to their clinical characteristics, tumor staging, and treatment modalities, and determined the independent prognostic factors affecting survival. Results: The patients were aged 59±10 years (mean±SD). During the follow-up period, 223 patients (86.8%) died and the overall median survival was 10.8 months; the 1-, 3-, and 5-year survival rates were 44.4%, 21.0%, and 12.1%, respectively. The outcomes in patients with tumor node metastasis (TNM) stage I or II and Child-Pugh class A or B were significantly better with surgical resection than with other treatment modalities (P<0.01). Patients who underwent supplementary transcatheter arterial chemoembolization as a second-line treatment after surgical resection had better outcomes than those who underwent surgical resection alone (P=0.02). Initial symptoms, Child-Pugh class, serum alpha-fetoprotein, tumor size, portal vein thrombosis, and TNM stage were found to be independent prognostic factors for survival among HCC patients. Conclusions: This retrospective cohort study elucidated survival outcomes and prognostic factors affecting survival in HCC patients at a single center.

Optimal time for repeating the IgM anti-hepatitis A virus antibody test in acute hepatitis A ...

Fri, 23 Mar 2012 00:00:01 +0100

Background/Aims: The nonspecific clinical presentation of acute hepatitis A (AHA) mandates the detection of anti-hepatitis A virus IgM antibodies (IgM anti-HAV) in the serum for obtaining a definitive diagnosis. However, IgM anti-HAV might not be present during the early phase of the disease. The aim of this study was to determine the optimal time for repeating the IgM anti-HAV test (HAV test) in AHA patients with a negative initial test. Methods: In total, 261 patients hospitalized with AHA were enrolled for this retrospective study. AHA was diagnosed when the test for IgM anti-HAV was positive and the serum alanine aminotransferase (ALT) level was ≥400 IU/L. Repeat HAV test was conducted after 1-2 weeks if the initial HAV test was negative but AHA was still clinically suspected. Results: The results of the initial HAV test were negative in 28 (10.7%) patients. The intervals from symptom onset to the initial-HAV-test day and from the peak-ALT day to the initial-HAV-test day were significantly shorter in the negative-initial-HAV-test group, but on multivariate analysis only the latter was significantly associated with negative results for the initial HAV test (β=-0.978; odds ratio [95% confidence interval]=0.376 [0.189-0.747]; P=0.005). The HAV test was positive in all patients when it was performed at least 2 days after the peak-ALT day. Conclusions: The results of HAV tests were significantly associated with the interval from the peak-ALT day to the HAV-test day. The optimal time for repeating the HAV test in clinically suspicious AHA patients with a negative initial HAV test appears to be at least 2 days after the peak-ALT day.

Co-expression patterns of Notch1, Snail, and p53 in grade III hepatocellular carcinoma with ...

Fri, 23 Mar 2012 00:00:01 +0100

Background/Aims: We aimed to determine the association between the co-expression patterns of Notch1, Snail, and p53 proteins (NSP) and the postoperative prognosis of hepatocellular carcinoma (HCC). Methods: The immunoblot data for molecular expression (147 HCC/corresponding non-HCC tissues and 15 dysplastic nodules) and the sequencing data for p53 mutations (110 HCCs) were obtained from our previous study. Data analyses were restricted to cases with HCC differentiation grade III (n=47), due to its high p53 mutation rate. Results: Nineteen of the 47 patients (40.4%) -comprising 12 in the liver and 7 in distant organs-had relapsed at 1-2 years after surgery. There was no relationship between p53 mutation and postoperative recurrence in the grade III HCCs. Seven (87.5%) of the eight relapsed cases with Notch1, Snail, and p53 (wild) co-expression experienced recurrence only within the liver, and all tumors were smaller than 5 cm in diameter. Extrahepatic relapse occurred mostly in HCC patients with tumors larger than 5 cm in diameter, without any deviation in the NSP pattern. Conclusions: The results of this preliminary study suggest that the co-expression of Notch1, Snail, and p53 (wild) is not inferior to the patterns with p53 mutation as an indicator of postoperative recurrence of grade III HCC.

High efficacy of adefovir and entecavir combination therapy in patients with ...

Fri, 23 Mar 2012 00:00:01 +0100

Background/Aims: Newly developed and potent antiviral agents suffer from the problem of drug resistance. Multidrug resistance is a major impediment in the treatment of patients with chronic hepatitis B (CHB). In line with American Association for the Study of Liver Diseases guidelines, adefovir dipivoxil (ADV) add-on therapy is recommended in the case of lamivudine resistance, while tenofovir disoproxil fumarate (TDF) is recommended for ADV or entecavir (ETV) resistance. TDF is currently not available in Korea. ADV+ETV combination therapy may be a viable alternative to TDF in patients with either ADV or ETV resistance. However, the efficacy of ADV+ETV combination therapy in patients with CHB and multidrug resistance is unclear. This study investigated the efficacy of ADV+ETV combination therapy in patients with multidrug resistance. Methods: Twenty-five patients were enrolled and were administered ADV+ETV combination therapy for at least 6 months. Blood was drawn at baseline and at 3, 6, 9, and 12 months after commencing treatment, and the following blood parameters were analyzed: alanine transaminase, hepatitis B e-antigen (HBeAg), anti-hepatitis B e-antigen, and hepatitis B virus (HBV) DNA levels. The initial virological response (IVR) was defined as an HBV DNA level of <4 log10 copies/mL after 6 months of combination therapy. Results: The IVR rate was 76%. The proportion of patients with a high viral load (≥5.0 log) dropped from 76% at baseline to only 5% after 6 months of treatment. The biochemical response rate during the first 6 months was 71%. HBeAg was lost in 2 patients (10%). Conclusions: ADV+ETV combination therapy induced a good IVR in CHB patients who were refractory to more than 2 antiviral agents. This regimen may be a good alternative to TDF in Korea, where that drug is not available.

Drug rash with eosinophilia and systemic symptoms syndrome following cholestatic hepatitis A: ...

Fri, 23 Mar 2012 00:00:01 +0100

Hepatitis A virus (HAV) infections occur predominantly in children, and are usually self-limiting. However, 75-95% of the infections in adults are symptomatic (mostly with jaundice), with the illness symptoms usually persisting for a few weeks. Atypical manifestations include relapsing hepatitis, prolonged cholestasis, and complications involving renal injury. Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, drug-induced hypersensitivity reaction characterized by skin rash, fever, lymph-node enlargement, and internal organ involvement. We describe a 22-year-old male who presented with acute kidney injury and was diagnosed with prolonged cholestatic hepatitis A. The patient also developed DRESS syndrome due to antibiotic and/or antiviral treatment. To our knowledge, this is the first report of histopathologically confirmed DRESS syndrome due to antibiotic and/or antiviral treatment following HAV infection with cholestatic features and renal injury.

A case of isolated metastatic hepatocellular carcinoma arising from the pelvic bone

Fri, 23 Mar 2012 00:00:01 +0100

Reports of metastatic hepatocellular carcinoma (HCC) without a primary liver tumor are rare. Here we present a case of isolated HCC that had metastasized to the pelvic bone without a primary focus. A 73-year-old man presented with severe back and right-leg pain. Radiological examinations, including computed tomography (CT) and magnetic resonance imaging (MRI), revealed a huge mass on the pelvic bone (13×10 cm). He underwent an incisional biopsy, and the results of the subsequent histological examination were consistent with metastatic hepatocellular carcinoma. The tumor cells were positive for cytokeratin (AE1/AE3), hepatocyte paraffin 1, and glypican-3, and negative for CD56, chromogranin A, and synaptophysin on immunohistochemical staining. Examination of the liver by CT, MRI, positron-emission tomography scan, and angiography produced no evidence of a primary tumor. Radiotherapy and transarterial chemoembolization were performed on the pelvic bone, followed by systemic chemotherapy. These combination treatments resulted in tumor regression with necrotic changes. However, multiple lung metastases developed 1 year after the treatment, and the patient was treated with additional systemic chemotherapy.

A case of emphysematous hepatitis with spontaneous pneumoperitoneum in a patient with ...

Fri, 23 Mar 2012 00:00:01 +0100

An 80-year-old woman with hilar cholangiocarcinoma was hospitalized due to sudden-onset abdominal pain. Computed tomography revealed hepatic necrosis accompanied with emphysematous change in the superior segment of the right liver (S7/S8), implying spontaneous rupture, based on the presence of perihepatic free air. Although urgent percutaneous drainage was performed, neither pus nor fluids were drained. These findings suggest emphysematous hepatitis with a hepatic mass. Despite the application of intensive care, the patient’s condition deteriorated rapidly, and she died 3 days after admission to hospital. Liver gas has been reported in some clinical diseases (e.g., liver abscess) to be caused by gas-forming organisms; however, emphysematous hepatitis simulating emphysematous pyelonephritis is very rare. The case reported here was of fatal emphysematous hepatitis in a patient with hilar cholangiocarcinoma.

Ciliated hepatic foregut cyst

Jae Do Yang and Woo Sung Moon — Fri, 23 Mar 2012 00:00:01 +0100

A 65-year-old man was admitted to our hospital for the evaluation of an asymptomatic hepatic cyst detected incidentally during a health checkup. Serological tests for hepatitis B and hepatitis C virus were negative. All other parameters were normal. On contrast-enhanced computed tomography (CT) imaging, a 1.5 cm-sized, oval-shaped, low attenuated cystic lesion was demonstrated in hepatic segment IV, just beneath the hepatic surface. Internal attenuation of the lesion was slightly higher than that of simple cyst, possibly suggesting internal mucoid fluid or high protein content (Fig. 1).

MR imaging of hepatic lymphangioma

Fri, 23 Mar 2012 00:00:01 +0100

A case of primary hepatic lymphangioma with a microcystic component was incidentally found in a 75-year-old woman. Although ultrasonography (US) and computed tomography (CT) showed a mixed lesion including cystic and solid components, magnetic resonance imaging (MRI) demonstrated the morphologic characteristics of the lesion better than other modalities.

Body iron, serum ferritin, and nonalcoholic fatty liver disease

Jae-Jun Shim — Fri, 23 Mar 2012 00:00:01 +0100

NADPH oxidase mediated oxidative stress in hepatic fibrogenesis

Yong-Han Paik and David A. Brenner — Sun, 25 Dec 2011 00:00:01 +0100

NADPH oxidase (NOX) is a multicomponent enzyme complex that generates reactive oxygen species (ROS) in response to a wide range of stimuli. ROS is involved as key secondary messengers in numerous signaling pathways, and NADPH oxidases complex has been increasingly recognized as key elements of intracellular signaling of hepatic fibrogenesis. In the liver, NADPH oxidase is functionally expressed both in the phagocytic form and in the non-phagocytic form. The non-phagocytic NADPH oxidase complex is structurally and functionally similar to the phagocytic NADPH, resulting in reduction of molecular oxygen to generate superoxide. There are six homologous NOX proteins in the non-phagocytic forms of NADPH oxidase. An emerging concept is that both phagocytic and nonphagocytic NADPH oxidase components in hepatic stellate cells (HSCs) mediate hepatic fibrosis, suggesting its potential role as a pharmacological target for anti-fibrotic therapy. The molecular components and signaling pathways of various NADPH oxidase homologues that are critical for the fibrotic activity in HSCs need to be more clearly identified.

A tool for communication with decision-makers: limitations and utilization of studies on cost ...

Kun-Sei Lee — Sun, 25 Dec 2011 00:00:01 +0100

See Article on Page 274

Virologic response is not durable after adefovir discontinuation in lamivudine-resistant ...

Sun, 25 Dec 2011 00:00:01 +0100

Background/Aims: We investigated the durability of the biochemical and virologic responses after adefovir (ADV) discontinuation in lamivudine-resistant (LMV-R) chronic hepatitis B (CHB) patients, and the outcomes of ADV discontinuation compared to that of ADV maintenance. Methods: The indication for ADV treatment cessation was an undetectable level of hepatitis B virus (HBV) DNA documented on two occasions at least 6 months apart. All patients received additional ADV for at least 12 months after the confirmation of undetectable HBV DNA (Cobas TaqMan PCR assay, <70 copies/mL). Of 36 patients who had a sufficient ADV therapeutic effect, 19 discontinued ADV treatment, while the others maintained it. A virologic rebound was arbitrarily defined as the redetection of HBV DNA at a level higher than 10⁵ copies/mL. Results: In the ADV discontinuation group, ADV treatment and additional therapy were administered for medians of 33 months (range, 12-47 months) and 18 months, respectively. The patients were followed for a median of 12 months (range, 3-30 months) after ADV cessation. During that period, 18 of 19 patients (95%) experienced viral relapse. Viral rebound was observed in six patients (32%). However, 12 of 18 patients (67%) exhibited serum HBV DNA levels of less than 10⁵ copies/mL. Biochemical relapses were observed in four of the six patients with viral rebound. In the ADV maintenance group, patients were treated for a median of 53 months (range, 31-85 months), and 9 patients (53%) experienced viral breakthrough. Conclusions: During short-term follow-up after ADV discontinuation, most patients (95%) exhibited viral relapse, whereas and viral breakthrough occurred in about half of patients (53%) maintained on ADV therapy. Therefore, the durability of virologic response after ADV discontinuation in LMV-R patients was unsatisfactory. In addition, and viral breakthrough was not infrequent in the ADV continuation group.

Pretreatment serum HBsAg-to-HBV DNA ratio predicts a virologic response to entecavir in chronic ...

Sun, 25 Dec 2011 00:00:01 +0100

Background/Aims: Decay of hepatitis B surface antigen (HBsAg) titers has previously been shown to be predictive of a virologic response (VR), especially during peginterferon-alpha therapy. However, the role of HBsAg levels in predicting a VR to nucleos(t)ide analog therapy has not yet been established. In this study we sought to determine whether the VR can be predicted from HBsAg titers in nucleos(t)ide-naïve chronic hepatitis B (CHB) patients treated with entecavir. Methods: CHB patients who started entecavir as an initial antiviral therapy were enrolled in this study. Serum hepatitis B virus (HBV) DNA, HBsAg, and alanine aminotransferase levels were measured every 3 months during treatment. A VR was defined as undetectable serum HBV DNA titer by real-time PCR assay (<60 IU/mL). Results: Fifty-two patients were enrolled, and the median duration of treatment was 26 months (range 7-35 months). Forty-five patients achieved a VR; the cumulative VR rates at 3, 6, 12, and 24 months were 40%, 71.2%, 81.5%, and 88%, respectively. Baseline HBV DNA levels were significantly lower in patients with VR, whereas the HBsAg levels did not differ significantly between patients with or without VR. In a univariate analysis the cumulative VR rate was significantly higher in HBeAg negative patients and patients with an HBsAg/HBV DNA ratio above 0.56. However, in a multivariate analysis only an HBsAg/HBV DNA ratio above 0.56 was an independent predictor of VR (P=0.003). The area under the receiver operating characteristic curve was larger for the HBsAg/HBV DNA ratio than for either HBV DNA or HBsAg. Conclusions: Pretreatment HBsAg/HBV DNA ratio can predict a long-term VR to entecavir therapy in nucleos(t)ide-naïve CHB patients.

Socioeconomic costs of liver disease in Korea

Sunmi Lee, Woojin Chung, and Kyung-Rae Hyun — Sun, 25 Dec 2011 00:00:01 +0100

Background/Aims: This study analyzed the scale and trends of the social and economic costs of liver disease in Korea for the past 5 years. Methods: The social aspects of socioeconomic costs were projected for viral hepatitis (B15-B19), liver cirrhosis, malignant neoplasm of the liver (C22) and other liver diseases (K70-K76), as representative diseases by dividing costs into direct and indirect from 2004 to 2008. Direct costs include hospitalization, outpatient, and pharmacy costs in the health-care sector, and transportation and caregiver costs. Indirect costs include the future income loss due to premature death and the loss of productivity resulting from absence from work. Results: The social and economic costs of liver disease were projected to be KRW 5,858 billion in 2004, KRW 5,572 billion in 2005, KRW 8,104 billion in 2006, KRW 6,095 billion in 2007, and KRW 5,689 billion in 2008. The future income loss resulting from premature death is thus greatest, from 73.9% to 86.1%, followed by the direct medical costs, from 9.0% to 18.1%. The productivity loss resulting from absence from work accounts for 3.3-5.5%, followed by the direct nonmedical costs such as transportation and caregiver costs, at 1.5-2.5%. Conclusions: Among the socioeconomic costs of liver disease in Korea, the future income loss resulting from premature death is showing a decreasing trend, whereas direct medical costs are increasing dramatically.

Chemical pleurodesis for the management of refractory hepatic hydrothorax in patients with ...

Sun, 25 Dec 2011 00:00:01 +0100

Background/Aims: Hepatic hydrothorax in patients with decompensated liver cirrhosis is a challenging problem. Treatment with diuretics and intermittent thoracentesis can be effective in selected patients. However, there are few effective therapeutic options in patients who are intolerant of these therapies. This study investigated the clinical usefulness of chemical pleurodesis with or without video-assisted thoracoscopic surgery (VATS) for patients with refractory hepatic hydrothorax. Methods: Eleven consecutive patients with refractory hepatic hydrothorax who underwent chemical pleurodesis with or without VATS between July 2007 and February 2011 were enrolled in this study. The medical records and radiologic imagings of these patients were thoroughly reviewed. Results: The median number of chemical pleurodesis sessions performed was 3 (range: 2-10). Successful pleurodesis was achieved in 8 of the 11 patients (72.7%), 5 (62.5%) of whom remained asymptomatic and hydrothorax free for a median follow-up of 16 weeks (range: 2-52 weeks). Complications were low-grade fever/leukocytosis (n=11, 100%), pneumonia (n=1, 9.1%), pneumothorax (n=4, 36.4%), azotemia/acute renal failure (n=6, 54.6%), and hepatic encephalopathy (n=4, 36.4%). Five patients were suspected as having procedure-related mortality (45.5%) due to the occurrence of acute renal failure with hepatic failure. The overall survival was significantly longer in the success group than in the non-success group. Conclusions: Although chemical pleurodesis may improve the clinical symptoms and the radiologic findings in as many as 72.7% of patients with refractory hepatic hydrothorax, a significantly high prevalence of procedure-related morbidity and mortality hinders the routine application of this procedure for such patients.

Differences in the patterns and outcomes of enhanced viral replication between hepatitis C ...

Sun, 25 Dec 2011 00:00:01 +0100

Background/Aims: Enhanced replication of hepatitis C virus (HCV) is well described in the setting of moderate to severe immunosuppression. The aims of this retrospective study were to determine the incidence of enhanced HCV replication in hepatocellular carcinoma (HCC) patients undergoing transarterial chemolipiodolization (TACL) and to identify the factors associated with enhanced replication of HCV. The clinical pattern of enhanced HCV replication was compared with hepatitis B virus (HBV) reactivation during TACL. Methods: This study enrolled 49 anti-HCV-seropositive patients who were diagnosed with HCC between January 2005 and December 2010 and who underwent TACL using epirubicin and/or cisplatin with consecutive HCV RNA copies checked. For comparison, 46 hepatitis B surface antigen¹-positive patients with HCC who were treated with TACL were also enrolled. The frequency, associated factors, and clinical outcomes of enhanced HCV replication were analyzed and compared with those of HBV reactivation during TACL. Results: Enhanced replication of HCV occurred in 13 (26.5%) of the 49 anti-HCV-seropositive patients during TACL. Of these 13 patients, 4 developed hepatitis, but none of the subjects developed decompensation due to the hepatitis. No significant clinical factors for enhanced HCV replication during TACL were found. Compared with HBV reactivation, the frequency of hepatitis attributed to enhanced HCV replication was significantly lower than that for HBV reactivation (8.2% vs. 23.9%, P=0.036). Conclusions: TACL can enhance HCV replication; however, the likelihood of hepatitis and decompensation stemming from enhanced HCV replication was lower than that for HBV reactivation in patients undergoing TACL.

Clinical features of acute viral hepatitis B in Korea: a multi-center study

Sun, 25 Dec 2011 00:00:01 +0100

Background/Aims: The incidence of Hepatitis B has significantly declined since the introduction of an HBV vaccination program. The aim of this study was to investigate recent clinical features of acute viral hepatitis B (AVH-B) in Korea. Methods: A total of 2241 patients with acute viral hepatitis were enrolled and their data were collected from nine medical-centers between January 2006 and December 2009. Results: One hundred nineteen (5.3%) of the 2241 were diagnosed as AVH-B. Among 78 patients with AVH-B whose data were analyzed, 50 were male, and the mean age was 38.6 years. In an initial test, mean AST, ALT and total-bilirubin levels were 1296.2 IU/L, 2109.6 IU/L and 9.3 mg/dl, respectively. Positivity frequencies for HBeAg and anti-HBe were 55.1% and 67.9%, respectively, and the mean HBV DNA level was 5.2 log10 copies/ml. The mean length of hospitalization was 11.6 days. During follow-up, AST, ALT and total bilirubin levels were normalized or near-normalized in all patients without serious complications. Sixty-three of 66 (95.4%) patients showed HBsAg loss and 37 (56.1%) patients showed HBsAg seroconversion. Only 3 patients (4.5%) showed persistent hepatitis B viremia. There was no case of death or liver transplantation. Nine patients (11.3%) had received anti-viral agents and their clinical outcomes were not significantly different from those of patients treated without antiviral agents. Conclusions: The prevalence of AVH-B among acute hepatitis patients is relatively low in Korea. AVH-B infection can be cured without complications in almost all patients, regardless of antiviral treatment.

Osler-Weber-Rendu disease presenting with hepatocellular carcinoma: radiologic and genetic findings

Sun, 25 Dec 2011 00:00:01 +0100

This is a case report of a 68-year-old man with hepatocellular carcinoma (HCC) accompanied by hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, and hepatic vascular malformation. HHT is an autosomal dominant disorder of the fibrovascular tissue that is characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. HHT is caused by mutation of the genes involved in the signaling pathway of transforming growth factor-β, which plays an important role in the formation of vascular endothelia¹. Hepatic involvement has been reported as occurring in 30-73% of patients with HHT. However, symptomatic liver involvement is quite rare, and the representative clinical presentations of HHT in hepatic involvement are high-output heart failure, portal hypertension, nodular regenerative hyperplasia, and symptoms of biliary ischemia. Some cases of HCC in association with HHT have been reported, but are very rare. We present herein the characteristic radiologic and genetic findings of HHT that was diagnosed during the evaluation and treatment of HCC.

Metastatic hepatocellular carcinoma presenting as facial nerve palsy and facial pain

Sun, 25 Dec 2011 00:00:01 +0100

Facial nerve palsy due to temporal bone metastasis of hepatocellular carcinoma (HCC) has rarely been reported. We experienced a rare case of temporal bone metastasis of HCC that initially presented as facial nerve palsy and was diagnosed by surgical biopsy. This patient also discovered for the first time that he had chronic hepatitis B and C infections due to this facial nerve palsy. Radiation therapy greatly relieved the facial pain and facial nerve palsy. This report suggests that hepatologists should consider metastatic HCC as a rare but possible cause of new-onset cranial neuropathy in patients with chronic viral hepatitis.

Coinfection of hepatitis A virus genotype IA and IIIA complicated with autoimmune hemolytic ...

Sun, 25 Dec 2011 00:00:01 +0100

A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.

Biliary intraepithelial neoplasia: a case with benign biliary stricture

Wonkyung Jung and Baek-hui Kim — Sun, 25 Dec 2011 00:00:01 +0100

Biliary hamartoma presented as a single mass

Yong Moon Shin — Sun, 25 Dec 2011 00:00:01 +0100

The use of vaptan in hyponatremic patients with liver cirrhosis

Won Hyeok Choe — Sun, 25 Dec 2011 00:00:01 +0100

The diagnosis and treatment of primary biliary cirrhosis

Kyung-Ah Kim and Sook-Hyang Jeong — Sun, 25 Sep 2011 00:00:01 +0100

Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is various from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibody and histologic findings of nonsuppurative destructive cholangitis. Although the diagnosis is straightforward, it could be underdiagnosed because of its asymptomatic presentation, or underrecognition of the disease. UDCA in a dose of 13-15 mg/kg is the widely approved therapy which can improve the prognosis of patients with PBC. However, one-third of patients does not respond to UDCA therapy and may require liver transplantation. Every effort to diagnose PBC in earlier stage and to develop new therapeutic drugs and clinical trials should be made.

Durability of antiviral therapy for chronic hepatitis C after achieving sustained virological ...

Jeong Heo — Sun, 25 Sep 2011 00:00:01 +0100

See Article on Page 183

Durability of a sustained virological response in chronic hepatitis C patients treated with ...

Sun, 25 Sep 2011 00:00:01 +0100

Background/Aims: The reappearance rates of hepatitis C virus (HCV) RNA after a sustained virological response (SVR) have been reported to be 1-2%. We investigated the reappearance rate of HCV RNA after SVR in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN) and ribavirin. Methods: In total, 292 CHC patients who achieved an SVR after PEG-IFN and ribavirin treatment were included. They were treated with subcutaneous injections of either PEG-IFN-α 2a or 2b plus ribavirin orally. Liver function tests and qualitative HCV RNA assays were performed every 6 months during the follow-up period after an SVR. Results: Among the 292 patients, 224 (genotype 1, 92; genotype non-1, 132) were followed up for more than 6 months after SVR. These 224 patients were aged 48.1±11.5 years (mean±SD), and 129 of them were male. The median follow-up duration was 18 months (range 6-60 months). The reappearance rate of HCV RNA during follow-up was 0%. Two patients who achieved an SVR developed hepatocellular carcinoma during the follow-up period. Conclusions: An SVR was maintained in all CHC patients treated with PEG-IFN plus ribavirin during a median follow-up of 18 months. However, a screening test for hepatocellular carcinoma is needed for patients with an SVR.

The retrospective cohort study for survival rate in patients with advanced hepatocellular ...

Sun, 25 Sep 2011 00:00:01 +0100

Background/Aims: This study was conducted to investigate the assessment of treatment efficacy of radiotherapy (RT) and other therapeutic modalities compared with palliative care only for treatment with advanced hepatocellular carcinoma (HCC). Methods: From 2002 to 2010, based on the case of 47 patients with advanced HCC, we have investigated each patients' Child-Pugh's class, ECOG performance, serum level of alpha fetoprotein and other baseline characteristics that is considered to be predictive variables and values for prognosis of HCC. Out of overall patients, the 29 patients who had received RT were selected for one group and the 18 patients who had received only palliative care were classified for the other. The analysis in survival between the two groups was done to investigate the efficacy of RT. Results: Under the analysis in survival, the mean survival time of total patients group was revealed between 30.1 months and 45.9 months in RT group, while it was 4.8 months in palliative care group, respectively. In the univariate analysis for overall patients, there were significant factors which affected survival rate like as follows: ECOG performance, Child-Pugh's class, the tumor size, the type of tumor, alpha fetoprotein, transarterial chemoembolization, and RT. The regressive analysis in multivariate Cox for total patients. No treatment under radiotherapy and high level of Child-Pugh's class grade were independent predictors of worse overall survival rate in patients. In contrast, for the subset analysis of the twenty-nine patients treated with radiotherapy, the higher serum level of alpha fetoprotein was an independent predictors of worse overall survival rate in patients. Conclusions: We found that the survival of patients with advanced HCC was better with radiotherapy than with palliative care. Therefore, radiotherapy could be a good option for in patients with advanced HCC.

Clinical features and treatment efficacy of peginterferon alfa plus ribavirin in chronic ...

Sun, 25 Sep 2011 00:00:01 +0100

Background/Aims: Cross-sectional studies have documented that 2-10% of patients who are chronically infected with hepatitis C virus (HCV) are also positive for hepatitis B virus (HBV) surface antigen (HBsAg). Data related to HCV-HBV coinfection are lacking in Korea. This study evaluated the clinical characteristics, the treatment efficacy of peginterferon alfa plus ribavirin, and the changes induced by such treatment in HBV status in chronic hepatitis C (CHC) patients coinfected with HBV. Methods: Eighteen (2.37%) HBsAg-positive CHC patients were selected from among the 758 subjects from the K(G)yeonggi-Incheon Peginterferon alfa and ribavirin in chronic hepatitis C Treatment (KIPECT) study, which evaluated the treatment efficacy and safety of peginterferon alfa plus ribavirin in CHC patients. Data on changes in the status of HBV infections were obtained. Results: HCV genotype 1b was the most common (44%). The overall sustained virologic response rate was 72% in all patients, and 60% and 87.5% in genotypes 1 and 2, respectively. Two of the 18 patients were positive for HBeAg, and 15 had baseline HBV DNA level of less than 2,000 IU/mL. Two of the three whose levels exceeded this threshold showed no detectable DNA after treatment. After the completion of treatment, serum HBV DNA levels were increased in the two patients whose baseline HBV DNA levels were less than 2,000 IU/mL. Conclusions: The prevalence of HBV coinfection in CHC patients was 2.37% and most of the patients were inactive carriers. The treatment efficacy was similar to that of HCV mono-infection. Reactivation of HBV replication was observed in some patients after CHC treatment.

Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients

Sun, 25 Sep 2011 00:00:01 +0100

Background/Aims: We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease. Methods: Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR. Results: Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity. Conclusions: Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.

Effect of aldosterone on the amplification of oncolytic vaccinia virus in human cancer lines

Sun, 25 Sep 2011 00:00:01 +0100

Background/Aims: JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. Methods: Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. Results: Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na⁺/H⁺-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. Conclusions: Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H⁺ gradient.

Peginterferon alpha and ribavirin combination therapy in patients with hepatitis C ...

Sun, 25 Sep 2011 00:00:01 +0100

Background/Aims: Pegylated interferon (peginterferon) and ribavirin combination therapy is less effective and associated with a higher frequency of serious complications in chronic hepatitis C patients with cirrhosis than in noncirrhotic patients. This study evaluated the efficacy and tolerability of peginterferon and ribavirin treatment in patients with hepatitis C virus (HCV)-related cirrhosis. Methods: Eighty-six patients with clinically diagnosed liver cirrhosis were treated with either peginterferon alpha-2a (n=51) or peginterferon alpha-2b (n=35) plus ribavirin. The sustained virologic response (SVR) and adverse effects were analyzed retrospectively. Results: Of the 86 patients (55 males), 48 patients (55.8%) had HCV genotype 1 infection and 38 (44.2%) had genotype non-1 infection. The overall SVR rate was 34.9% (30/86), and the rates of SVR in the genotype 1 and non-1 patients were 20.8% (10/48) and 52.6% (20/38), respectively. The multivariate analysis revealed that having HCV genotype 1 (P=0.003) and high baseline viral load (>8.0×10⁵ IU/mL, P=0.012) were the independent predictive factors for SVR failure. In 20.9% (18/86) of the patients, treatment was not completed due to adverse events (27.8%), loss to follow-up (50.0%), and other reasons (22.2%). Conclusions: Peginterferon and ribavirin combination therapy was relatively effective and feasible for clinically diagnosed HCV patients, especially in those with genotype non-1 infection and low baseline viral load.

A case of leukemoid reaction in a patient with sarcomatous hepatocellular carcinoma

Sun, 25 Sep 2011 00:00:01 +0100

A leukemoid reaction is defined as reactive leukocytosis exceeding 50,000/mm³, with a significant increase in early neutrophil precursors, and can be a paraneoplastic manifestation of various malignant tumors. A 71-year-old male patient complained of decreased appetite, fatigue, and abdominal fullness. He had a palpable, firm liver, and laboratory investigations suggested leukemoid reaction. Liver dynamic computed tomography revealed a hypervascular mass, and an ultrasound-guided fine-needle aspiration of the mass confirmed hepatocellular carcinoma (HCC) with a sarcomatoid component. The leukocyte count of the patient had increased to 147,800/mm³, and he died 10 days after admission. This is a rare case of leukemoid reaction in a patient with sarcomatous HCC.

A case of amoxicillin-induced hepatocellular liver injury with bile-duct damage

Sun, 25 Sep 2011 00:00:01 +0100

Amoxicillin, an antibiotic that is widely prescribed for various infections, is associated with a very low rate of drug-induced liver injury; hepatitis and cholestasis are rare complications. Here we present a case of a 39-year-old woman who was diagnosed with abdominal actinomycosis and received amoxicillin treatment. The patient displayed hepatocellular and bile-duct injury, in addition to elevated levels of liver enzymes. The patient was diagnosed with amoxicillin-induced cholestatic hepatitis. When amoxicillin was discontinued, the patient’s symptoms improved and her liver enzyme levels reduced to near to the normal range.

Transcatheter coil embolization of the inferior epigastric artery in a huge abdominal wall ...

Sun, 25 Sep 2011 00:00:01 +0100

Therapeutic paracentesis is considered to be a relatively safe procedure and is performed commonly for the control of massive ascites in patients with liver cirrhosis. The commonest puncture site, approximately 4 or 5 cm medial of left anterior superior iliac spine, can be located across the route of the inferior epigastric artery, which is one of the sites of potential massive bleeding. In a 46-year-old woman with liver cirrhosis and refractory ascites, a huge abdominal wall hematoma developed after therapeutic paracentesis. The patient was not stabilized by conservative treatment, and inferior epigastric artery injury was confirmed on angiography. Angiographic coil embolization of the inferior epigastric artery was conducted, after which the bleeding ceased and the hematoma stopped growing. This case indicates that physicians performing paracentesis should be aware of the possibility of inferior epigastric artery injury and consider early angiographic coil embolization when a life-threatening abdominal wall hematoma develops.

Early hepatocellular carcinoma

So-Young Jin and In Ho Choi — Sun, 25 Sep 2011 00:00:01 +0100

Sclerosing hemangioma in the liver

Yong Moon Shin — Sun, 25 Sep 2011 00:00:01 +0100

Apoptosis and diagnosis of nonalcoholic steatohepatitis

Chang Wook Kim and Chang Don Lee — Sun, 25 Sep 2011 00:00:01 +0100

Epidemiology and prevention of hepatitis B virus infection

So Young Kwon, Chang Hong Lee — Wed, 15 Jun 2011 00:00:01 +0100

Hepatitis B virus (HBV) infection has been a major global cause of morbidity and mortality. The recognition of the problem led to a worldwide effort to reduce transmission of HBV through routine infant vaccination. HBV infection is the most common cause of chronic liver diseases and hepatocellular carcinoma in Korea. After hepatitis B vaccine era, seroprevalence of hepatits B surface antigen is decreasing, particularly in children. Hepatitis B vaccine is remarkably safe and shows high immunogenicity. Universal childhood immunization with three doses of hepatitis B vaccine in the first year of life is a highly effective method for prevention and control of hepatitis B.

Percutaneous interventional procedures in an era of liver transplantation

Young Seok Kim — Sat, 25 Jun 2011 00:00:01 +0100

See Article on Page 106

A study of the awareness of chronic liver diseases among Korean adults

Mon, 07 Mar 2011 00:00:01 +0100

Background/Aims: Chronic liver disease is closely associated with lifestyle, and public enlightenment of the lifestyle factors is important in reducing prevalence of chronic liver disease. The KASL (Korean Association for the Study of the Liver) conducted a survey of basic information and epidemiological data regarding chronic liver diseases. Methods: A survey of chronic liver disease involving a total of 2,794 respondents was conducted. The respondents included patients and their guardians, visitors for health check-ups, and online pollees who completed a questionnaire on the awareness of fatty liver or chronic liver disease. Results: Of the entire cohort, 854 (39.7%) said they have had or still have fatty liver or an elevated transaminase level (>40 IU/L), but only 23.4% of the respondents had visited a hospital. It was found that 35% of healthy subjects and 45% of patients and their guardians misunderstood hepatitis B as the hereditary disesase. Furthermore, 26% of the subjects responded that patients with inactive hepatitis B do not require regular follow-up. While 17.9% answered that it is not too late to test for liver cancer when symptoms arise, 38.8% believed that liver transplant in liver cancer patients has a low success rate and is thus not recommended. Conclusions: Despite the inundation of information and widespread media advertising, the awareness of chronic liver disease is unsatisfactory among Korean adults. Systematic nationwide studies are needed to obtain data and information regarding the prevalence of chronic liver disease and patterns of use of the health-care system.

Treatment and clinical outcome of needle-track seeding from hepatocellular carcinoma

Tue, 22 Mar 2011 00:00:01 +0100

Background/Aims: Needle-track seeding is a rare but important complication of diagnostic and therapeutic ultrasound (US)-guided procedures in hepatocellular carcinoma (HCC). We examined the frequency of needle-track seeding after US-guided percutaneous ethanol injection (PEI), fine-needle aspiration biopsy (FNAB), and percutaneous transhepatic biliary drainage (PTBD) in order to determine the appropriate treatment for needle-track seeding and its clinical outcome. Methods: We analyzed the clinical characteristics and treatment outcomes in eight patients who experienced needle-track seeding from HCC after an US-guided procedure (FNAB, PEI, or PTBD) between January 1990 and July 2004. Results: Seven (0.14%) of 5,092 patients who experienced needle-track seeding (2 after PEI, 4 after FNAB, and 1 after PTBD) during the study period and 1 other patient who experienced needle-track seeding recently were recruited for this study. Two of the eight patients underwent mass excision and the other six patients underwent en-bloc wide excision for the needle-track seeding. Tumors recurred in the needletracks in both patients who underwent mass excision but not in the six patients who underwent en-bloc wide excision. Mortality occurred in three patients who experienced the recurrence and progression of intrahepatic HCC. Conclusions: The incidence of needle-track seeding after US-guided procedures in HCC was 0.14%. En-bloc wide excision seems to be the optimal treatment for minimizing the probability of tumor recurrence due to needle-track seeding.

Applicability of the BCLC staging system to patients with hepatocellular carcinoma in Korea: ...

Thu, 22 Apr 2010 00:00:01 +0100

Background/Aims: The Barcelona Clinic Liver Cancer (BCLC) staging system is logical for the staging and treatment of hepatocellular carcinoma (HCC) because it was based on survival data. This study evaluated the applicability of the BCLC staging system and reasons for divergence from BCLC-recommended treatments in Korean HCC patients. Methods: One hundred and sixty consecutive HCC patients were prospectively enrolled. Treatments were generally recommended according to the guideline of the American Association for the Study of Liver Diseases, but patients were also informed about alternative treatments. The final decision was made with patient agreement, and was based on the doctor’s preferences when a patient was unable to reach a decision. Results: There were 2 (1%), 101 (64%), 20 (12.5%), 34 (21.5%), and 3 (1%) patients with very early-, early-, intermediate-, advanced-, and terminal-stage disease, respectively. Only 64 patients (40%) were treated according to BCLC recommendations. The treatment deviated from BCLC recommendations in 68% (69/101) and 79% (27/34) of patients with early and advanced stage, respectively. The main causes of deviation were refusal to undergo surgery, the presence of an indeterminate malignancy nodule, the absence of a suitable donor, or financial problems. Conclusions: Donor shortage, financial problems, the relatively limited efficacy of molecular targeting agents, and the presence of an indeterminate nodule were the main causes of deviation from BCLC recommendations. Even after excluding cases in which decisions were made by patient preference, only 66% of the HCC patients were treated according to BCLC recommendations. Treatment guidelines that reflect the Korean situation are mandatory for HCC patients.

Combination treatment with intrahepatic arterial infusion and intratumoral injection ...

Sat, 20 Nov 2010 00:00:01 +0100

Background/Aims: Combination treatment consisting of hepatic arterial infusion chemotherapy with epirubicin and cisplatin (HAIC-EC) and systemic infusion of low-dose 5-fluorouracil (5-FU) are sometimes effective against advanced hepatocellular carcinoma (HCC). However, there is no effective treatment for advanced HCCs with arterioportal shunts (APS) or arteriovenous shunts (AVS). Methods: We investigated a response and adverse events of a new combination protocol of repeated HAIC-EC and percutaneous intratumoral injection chemotherapy with a mixture of recombinant interferon-gamma (IFN-γ) and 5-FU (PIC-IF) in patients with far-advanced HCCs with large APSs or AVSs. Results: There was a complete response (CR) for the large vascular shunts in all three patients and for all tumor burdens in two patients. Significant side effects were flu-like symptoms (grade 2) and bone marrow suppression (grade 2 or 3) after each cycle, but these were well-tolerated. Conclusions: These results suggest that the combination of HAIC-EC and PIC-IF is a new and promising approach for advanced HCC accompanied by a large APS or AVS.

Serum cystatin C level is a useful marker for the evaluation of renal function in patients ...

Mon, 30 May 2011 00:00:01 +0100

Background/Aims: Several studies suggested that serum cystatin C (CysC) is more useful than serum creatinine (Cr) for the assessment of renal function in patients with liver cirrhosis. This study evaluated the clinical significance of CysC in patients with cirrhotic ascites and normal Cr level. Methods: We enrolled patients with cirrhotic ascites and a normal serum Cr level (<1.2 mg/dL). GFR was measured by ^99mTc- DTPA renal scan. Serum Cr, CysC, and Cr clearance (CCr) were measured on the same day. Significant renal impairment and severe renal impairment were defined as GFR <60 mL/min and GFR <30 mL/min, respectively. Results: Eighty-nine patients with cirrhotic ascites were enrolled in the study (63 men and 26 women; age, 55±11 years). Forty-seven (52.8%) and 42 (47.2%) patients were in Child-Pugh grade B and C, respectively. Serum Cr and CysC levels and GFR were 0.8±0.2 mg/dL, 1.1±0.3 mg/L, and 73.4±25.5 mL/min, respectively. Significant and severe renal impairment were noted in 28 (31.5%) and 2 (2.2%) patients, respectively. GFR was well correlated with serum Cr, CysC, and e-GFR_MDRD, while it was not correlated with e-GFR_C&G. In multivariate analysis, only CysC was significantly correlated with GFR (β, 45.620; 95% CI, 23.042-68.198; P<0.001). Serum CysC level was the only independent predictor for significant renal impairment. Conclusions: Significant renal dysfunction was not rare in patients with cirrhotic ascites, even their serum Cr level is normal. Serum CysC is a useful marker for detecting significant renal dysfunction in these patients.

The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats

Seon Ok Min, Sung Hoon Kim, Sang Woo Lee, Jin A Cho3, and Kyung Sik Kim — Mon, 30 May 2011 00:00:01 +0100

Background/Aims: Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats. Methods: To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed. Results: Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100× magnification (cells/field) were 31.8±24.2 in NC, 69.0±72.3 in TC, 80.2±63.1 in IP, and 21.2±20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400× were 3.4±6.0 in NC, 16.9±69 in TC, 17.0±7.8 in IP and 7.4±7.6 in IC (P<0.05). Conclusions: Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting.

A case of hemocholecyst associated with hemobilia following radiofrequency ablation therapy ...

Wed, 22 Dec 2010 00:00:01 +0100

Radiofrequency ablation (RFA) is performed as an alternative to surgical resection for primary or secondary liver malignancies. Although RFA can be performed safely in most patients, early and late complications related to mechanical or thermal damage occur in 8-9.5% cases. Hemocholecyst, which refers to hemorrhage of the gallbladder, has been reported with primary gallbladder disease or as a secondary event associated with hemobilia. Hemobilia, defined as hemorrhage in the biliary tract and most commonly associated with accidental or iatrogenic trauma, is a rare complication of RFA. Here we report a case of hemocholecyst associated with hemobilia after RFA for hepatocellular carcinoma that was successfully managed by laparoscopic cholecystectomy.

Ruptured duodenal varices arising from the main portal vein successfully treated with ...

Tue, 28 Dec 2010 00:00:01 +0100

Duodenal varices result from retroperitoneal portosystemic shunts that usually come from the pancreaticoduodenal vein and drain into the inferior vena cava. Because they are a rare but fatal cause of gastrointestinal bleeding, a prompt hemostatic intervention is mandatory. A 62-year-old man who had a history of excessive alcohol consumption presented with massive hematemesis and melena. Emergent endoscopy revealed ruptured varices with an adhering whitish fibrin clot on the postbulbar portion of the duodenum. Abdominal computed tomography demonstrated a cirrhotic liver with venous collaterals around the duodenum and extravasated contrast in the second and third portions. The collaterals originated from the main portal vein and drained via the right renal vein into the inferior vena cava. Endoscopic injection sclerotherapy with cyanoacrylate was successful in achieving hemostasis, and resulted in the near eradication of duodenal varices at a 6-month follow-up.

Metronidazole-induced encephalopathy in a patient with liver cirrhosis

Fri, 01 Apr 2011 00:00:01 +0100

Encephalopathy is a disorder characterized by altered brain function, which can be attributed to various causes. Encephalopathy associated with metronidazole administration occurs rarely and depends on the cumulative metronidazole dose, and most patients with this condition recover rapidly after discontinuation of therapy. Because metronidazole is metabolized in the liver and can be transported by the cerebrospinal fluid and cross the blood-brain barrier, it may induce encephalopathy even at a low cumulative dose in patients with hepatic dysfunction. We experienced a patient who showed ataxic gait and dysarthric speech after receiving metronidazole for the treatment of hepatic encephalopathy that was not controlled by the administration of lactulose. The patient was diagnosed as metronidazole-induced encephalopathy, and stopping drug administration resulted in a complete recovery from encephalopathy. This case shows that caution should be exercised when administering metronidazole because even a low dose can induce encephalopathy in patients with liver cirrhosis.

Cholangiocarcinoma arising in von Meyenburg complexes

Hee Kyung Kim, So-Young Jin — Sat, 25 Jun 2011 00:00:01 +0100

Posttransplantation lymphoproliferative disorder involving liver after renal transplantation

Yong Moon Shin — Sat, 25 Jun 2011 00:00:01 +0100

Role of vitamin D in chronic hepatitis C

Tae Yeob Kim — Sat, 25 Jun 2011 00:00:01 +0100

Chronic hepatitis B in pregnancy: unique challenges and opportunities

Kumaresan Yogeswaran, Scott K. Fung — Fri, 25 Mar 2011 00:00:01 +0100

Chronic hepatitis B (CHB) affects 350 million individuals worldwide. Perinatal transmission leads to high rates of chronic infection and complications, including cirrhosis and hepatocellular carcinoma. It is important to recognize and appropriately treat CHB in pregnancy, thereby reducing the risk of neonatal transmission and HBV-associated morbidity and mortality. Screening for CHB is recommended in all pregnant mothers as is universal vaccination of infants with hepatitis B virus (HBV) vaccine with or without hepatitis B immunoglobulin (HBIG). This has resulted in a lower incidence of HBsAg seropositivity and HCC in regions where universal infant vaccination has been endorsed. Mode of delivery and breastfeeding do not appear to affect HBV transmission rates based on available data. Overall, CHB does not increase perinatal maternal-fetal mortality. Administration of oral antiviral therapy during the third trimester to HBsAg-positive mothers with HBV DNA≥7 log IU/mL may be useful in preventing breakthrough infection. Treatment may be considered earlier in pregnancy for persistently active liver disease shown by high ALT, HBV DNA levels and/or significant hepatic fibrosis. Lamivudine, tenofovir and telbivudine are safe and effective and are the agents of choice in pregnancy. However, further clinical studies are necessary to elucidate the role of antiviral therapy in the pregnant HBV carrier.

Liver function tests as indicators of metabolic syndrome

Han Chu Lee — Fri, 25 Mar 2011 00:00:01 +0100

See Article on Page 27

Nonalcoholic fatty liver disease (NAFLD) is no longer considered to be a normal physiologic condition without any clinical significance. It is now widely accepted that nonalcoholic steatohepatitis (NASH), a type of fatty liver disease, can progress to end-stage liver disease and increase the risk of mortality. In addition, NAFLD patients are associated with a significantly higher overall mortality as well as liver-related mortality compared to the age- and gender-adjusted general population.^1,2 Accordingly, several studies have been conducted to redefine the normal ranges of liver function tests, especially alanine aminotransferase (ALT) levels considering the influence of NAFLD on serum ALT level. However, there are two different ways to interpret ALT levels. Piton et al suggested that these levels should be interpreted with respect to the body mass index (BMI) considering the positive association between ALT level and BMI.³ However, this concept was questioned by Prati et al⁴ since NAFLD itself is not necessarily a benign liver disease without clinical significance. The normal range of ALT levels is significantly lower than the conventional cut-off levels (41 IU/L for men and 30 U/L for women) if patients with risk factors for NAFLD are excluded. This finding was also observed in a Korean population in which patients with NAFLD were excluded histologically.⁵ Another important study from Korea also showed a positive association between ALT level even within the normal range by conventional criteria and liver-related mortality.⁶ All these findings suggested that the normal range of ALT level (along with those of other liver function test factors) should be adjusted. However, several points should be considered before applying the revised upper limit of normal serum ALT levels. A study by Oh et al⁷ reported that the incidence of metabolic syndrome and NAFLD correlates with ALT and γ-glutamyltransferase (GGT) levels within the conventional reference ranges. About half of the subjects with ALT levels in the upper fourth quartile of the conventional normal range had fatty liver disease that appeared on ultrasonography. This finding strongly suggests that adjustment of the normal range for ALT level can increase the detection rates of patients with NAFLD. However, the study population consisted of individuals who underwent health check-ups voluntarily, and therefore could have introduced selection biases. Another unanswered question is what proportion of patients with NAFLD actually has histologically-diagnosed NASH. It is generally accepted that liver-related mortality does not increase in patients with simple steatosis. We do not and probably cannot conclusively determine if this is actually the case in near future since liver biopsy is still the only test that can differentiate NASH from simple steatosis. The incidence of NASH was reported to be 2.2% among Korean living liver donors among whom the overall incidence of NAFLD was 51.4%.⁸ Therefore, the prevalence of NASH among individuals with NAFLD is estimated to be 4.3%. Since this study included patients with ALT level elevated up to 120 IU/L, the proportion of NASH cases may be different (probably lower) among fatty liver disease patients with normal ALT level as defined by conventional criteria. Therefore, further studies are needed to investigate whether the adjustment of the normal range of ALT levels is cost-effective or can reduce long-term liver-related mortality. Secondly, ALT or GGT (and other liver function tests) is primarily used for screening for liver disease and to determine the appropriate treatment for patients with liver diseases. Several follow-up studies have demonstrated that elevated ALT or GGT level is associated with increased overall mortality including death from cardiovascular disease or cancers and/or liver-related mortality.^9,10 However, even though serum ALT and GGP levels may predict the development of metabolic syndrome or increased mortality, adoption of these tests to screen for metabolic syndrome or other diseases is quite a different story. For practical reasons, serum ALT or GGT levels are never used as an isolated test to screen for liver disease or other diseases in Korea. For example, the tests for routine health check-ups sponsored by the National Health Insurance Cooperation in Korea include height, weight, BMI, blood pressure, fasting blood glucose, total cholesterol, aspartate aminotransferase, and ALT and GGT levels. In addition, many other programs also include tests for serum HBsAg or anti-HCV antibodies. Although serum ALT or GGT level within the reference limits can predict the development of metabolic syndrome or future mortality rates, other parameters including BMI, blood pressure, fasting blood glucose levels, and total cholesterol levels, or combinations of these factors are probably more informative. Furthermore, in the study by Oh et al,⁷ serum ALT or GGT level was used to predict the presence of pre-existing metabolic syndrome, but their usefulness in predicting the development of metabolic syndrome or mortality is unknown. Therefore, it is still unclear whether the use of serum ALT or GGT levels within the upper fourth quartile of the conventional normal range is in fact helpful for detecting metabolic syndrome or predicting mortality in ordinary clinical practice. Thirdly, it is still unknown whether the increase in liver-related deaths in Korean people with slightly higher aminotransferase activity that still within the normal range can be attributed to NAFLD or other liver diseases including autoimmune hepatitis or Wilson’s disease.⁶ In the study by Kim et al,⁶ serum HBsAg and/or anti-HCV antibody levels were not tested, and the presence of underlying liver cirrhosis was excluded only by a self-report questionnaire. History of alcohol abuse was also obtained only by the self-report questionnaire. Therefore, it is still unknown whether the increased number of liver-related deaths was caused by unreported chronic hepatitis B virus (HBV) infection and/or alcohol- related cirrhosis, or by other liver diseases including NAFLD, cryptogenic liver disease, autoimmune hepatitis, or Wilson’s disease. Given that Korea is an area with endemic chronic HBV infection and high rates of alcohol abuse, the former scenario is more likely. Therefore, the clinical benefit from improved detection of NAFLD by a revised normal range of ALT or GGT is largely unknown, and should be addressed by future studies. In conclusion, many studies have demonstrated that the conventional normal range of ALT level or those of other liver function test factors should be adjusted to account for the influence of NAFLD. In addition, emerging data have suggested that serum ALT activity may serve not only as a marker of liver diseases but also as an indicator of metabolic syndrome or general health. However, despite its potential role as an indicator of NAFLD or metabolic syndrome even within the conventional reference ranges, it is still unknown whether the adjustment of the normal cut-off level of ALT can help reduce liver-related or overall mortality rates with acceptable cost-effectiveness. Future studies are needed to address this issue.

Clinicopathologic significance of the expression of Snail in hepatocellular carcinoma

Fri, 25 Mar 2011 00:00:01 +0100

Background/Aims: E-cadherin is involved in intercellular binding and cellular polarity formation. Snail is a key regulator of the epithelial-mesenchymal transition and is closely associated with tumor invasiveness due to its ability to suppress E-cadherin expression. We investigated the expressions of E-cadherin and Snail in hepatocellular carcinoma (HCC) tissue to determine the clinical significance of these proteins in HCC. Methods: Immunohistochemistry was used to examine the expressions of E-cadherin and Snail in resected tissues from 59 patients diagnosed with HCC. We also evaluated the relationship between the expressions of these two molecules in HCC tissue and clinicopathologic factors in the patients. Results: Immunohistochemistry showed that Snail was stained in 20.3% of the HCC tissues and 3.4% of noncancerous tissues. Snail was not stained in the area of E-cadherin expression. The expression of Snail in the HCC tissue was associated with poorly differentiated HCC (P=0.028). The expression of Snail without E-cadherin staining in HCC tissue was significantly associated with postoperative HCC recurrence (P=0.013). Conclusions: The expression of Snail in HCC tissue was associated with decreased expression of E-cadherin and poorly differentiated HCC. The expression of Snail without E-cadherin staining in HCC was associated with postoperative recurrence.

Development and validation of a simple index system to predict nonalcoholic fatty liver disease

Fri, 25 Mar 2011 00:00:01 +0100

Background/Aims: Abdominal ultrasonography is useful for the detection and diagnosis of nonalcoholic fatty liver disease (NAFLD). The aims of this study were to establish a predictive model for the selection of subjects for abdominal ultrasonography for the diagnosis of NAFLD and to assess validity of the model. Methods: The subjects included 901 people who visited the health examination center of the Busan Medical Center. We conducted multiple logistic regression analyses of potential risk factors to identify independent risk factors for NAFLD, and developed an index system. Results: Four independent risk factors were identified. The index system was developed by assigning 1 clinical scoring point to approximately 0.7 logistic regression coefficients to each factor as follows: alanine aminotransferase/aspartate aminotransferase ratio >1.5 (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.21-4.07; P=0.010), 1 point; γ-glutamyl transpeptidase >50 (OR, 2.15; 95% CI, 1.13-4.07; P=0.019), 1 point; triglyceride >150 mg/dL (OR, 1.92; 95% CI, 1.14-3.24; P=0.015), 1 point; 23 kg/m²≤BMI<25 kg/m² (OR, 3.68; 95% CI, 2.05-6.63; P<0.001), 2 points; and BMI 25 kg/m² (OR, 7.65; 95% CI, 4.29-13.62; P<0.001), 3 points. The area under the receiver operating characteristics curve was 0.797 (95% CI, 0.751-0.842), and when 3 points was used as a cut-off value, the sensitivity and specificity were 71.7% and 75.9%, respectively. Conclusions: NAFLD can be predicted through the clinical application of the index system established herein. If abdominal ultrasonography is used for high-risk patients, NAFLD will be diagnosed and managed in its early stage.

Association of serum alanine aminotransferase and

Fri, 25 Mar 2011 00:00:01 +0100

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) has recently been found to be a novel component of metabolic syndrome (MS), which is one of the leading causes of chronic liver disease. The serum alanine aminotransferase (ALT) and γ -glutamyltransferase (GGT) levels are suggested to affect liver fat accumulation and insulin resistance. We assessed the associations of serum ALT and GGT concentrations within the reference ranges with MS and NAFLD. Methods: In total, 1,069 subjects enrolled at the health promotion center of Wonkwang University Hospital were divided into 4 groups according to serum ALT and GGT concentrations levels within the reference ranges. We performed biochemical tests, including liver function tests and lipid profiles, and diagnosed fatty liver by ultrasonography. Associations of ALT and GGT concentrationgrading within the reference range with fatty liver and/or MS were investigated. Results: The presence of MS, its components, and the number of metabolic abnormalities [except for high-density lipoprotein-cholesterol (HDL-C) and fasting blood glucose] increased with the ALT level, while the presence of MS, its components, and the number of metabolic abnormalities (except for HDL-C) increased with the GGT level. The odds ratios for fatty liver and MS increased with the ALT level (P<0.001 and P=0.049, respectively) and the GGT level (P=0.044 and P=0.039, respectively). Conclusions: Serum ALT and GGT concentrations within the reference ranges correlated with the incidence of NAFLD and MS in a dose-dependent manner. There associations need to be confirmed in large, prospective studies.

Genetic polymorphism at codon 10 of the transforming growth factor-

Fri, 25 Mar 2011 00:00:01 +0100
Background/Aims: Transforming growth factor beta1 (TGF-β1) is a key cytokine in the production of extracellular matrix. A genetic polymorphism at codon 10 of the TGF-β1 gene is associated with liver fibrosis. We investigated the effect of genetic polymorphisms at codon 10 on the development of alcoholic liver cirrhosis (ALC). Methods: In total, 119 controls and 182 patients with ALC, were enrolled in the study. Clinical and laboratory data including total lifetime alcohol intake were collected at enrollment. The genotype at codon 10 was determined for each patient by single-strand conformation polymorphism. Results: There were three types of genetic polymorphism at codon 10: homozygous proline (P/P), heterozygous proline/leucine (P/L), and homozygous leucine (L/L). Among the controls, the proportions of P/P, P/L, and L/L were 26.1%, 44.5%, and 29.4%, respectively in the ALC group, these proportions were 23.1%, 43.4%, and 33.5%, respectively. The genotype distribution did not differ between the controls and the ALC group. In the ALC group, age, total lifetime alcohol intake, and distribution of Child-Pugh class did not differ with the genotype. Of the male patients with ALC (n=164), the proportions of P/P, P/L, and L/L were 20.1%, 44.5%, and 35.4%, respectively the genotype distribution did not differ between the male controls and the male ALC patients. Conclusions: The genotype at codon 10 in TGF-β1 does not appear to influence the development of ALC. Further study is needed to investigate other genetic factors that influence the development of ALC in patients with chronic alcohol intake.

A nationwide seroprevalence of total antibody to hepatitis A virus from 2005 to 2009: age and ...

Fri, 25 Mar 2011 00:00:01 +0100
Background/Aims: Recent outbreak of hepatitis A in Korea is clearly related to the epidemiological shift of hepatitis A virus (HAV). However, nationwide seroprevalence data have been limited. This study estimated the nationwide, age- and area-adjusted anti-HAV prevalence from 2005 to 2009. Methods: Retrospective analysis of the results of total anti-HAV test in 25,140 cases which were requested by 1,699 medical institutions throughout the nation to Seoul Clinical Laboratory from Jan. 1 2005 to Dec. 31 2009 was performed. The estimated seroprevalence was adjusted by area and age of the standard population based on the 2005 Census data from Korea National Statistical Office. Results: The area-adjusted anti-HAV prevalence in the children younger than 10 years were 33.4% in 2005 and 69.9% in 2009. The most susceptible age groups to HAV infection during the last 5 years were teenagers and the young adults in their age of twenties. The area-adjusted seroprevalence in 2009 were 11.9% in the age group of 20-29 years, 23.4% in the age group of 10-19 years, 48.4% in the age group of 30-39 years. The population in 40-49 years showed geographically different seroprevalence with the lowest rate in Seoul (80%). Conclusions: The most susceptible age group to HAV infection is 10-29 years, while the young children less than 10 years showed about 70% seropositivity. The changing seroepidemiology should be monitored continuously for the proper vaccination and patient care.

Optimal technique and response of doxorubicin beads in hepatocellular cancer: bead size and dose

Fri, 25 Mar 2011 00:00:01 +0100
Background/Aims: It has been shown that the drug-eluting beads loaded with doxorubicin (DEBDOX) are effective for the treatment of hepatocellular carcinoma (HCC). However, the optimal safety and efficacy still remain to be established by using various bead sizes, doxorubicin doses, and the degree of stasis.The aim of this study was to determine the optimal safety and efficacy of DEBDOX in the treatment of HCC. Methods: Analysis of a 503-patient prospective, multicenter, multinational Bead Registry Database from 2007 to 2010 identified 206 patients who had been treated for HCC with DEBDOX. Primary endpoints were to compare safety, tolerance, response rates, and overall survival based on bead size (100-300, 300-500, 500-700, and 700-900 μm), number of vials, doxorubicin dose, and degree of stasis. Results: In total, 206 patients underwent 343 treatments. The use of all four bead sizes was similar based on Child-Pugh class and Okuda stage, with a significantly higher use (50%) of beads of size 100-300 μm in patients with portal vein thrombosis (P=0.05). Significant differences were seen for the number of median treatments, median doxorubicin dose, lobar infusion), and degree of complete stasis. The rate of adverse events was higher for larger beads than for smaller beads (28% vs. 16%; P=0.02). Conclusions: Bead size and dose may vary according to disease distribution. Smaller beads offer the opportunity for repeated treatments, a larger cumulative dose delivery, a lesser degree of complete stasis, and fewer adverse events.

Vogt-Koyanagi-Harada disease occurring during pegylated interferon-

Fri, 25 Mar 2011 00:00:01 +0100
Vogt-Koyanagi-Harada (VKH) disease is a multisystem syndrome characterized by ocular (uveitis and retinal detachment), neurological (headache, tinnitus, and meningitis), and integumentary (vitiligo, alopecia, and poliosis) involvement. Although the pathogenesis of VKH disease is not well understood, an autoimmune T-cell response to a melanocyte-associated antigen is considered to be a cause of VKH disease. The complex immunological response to interferon and ribavirin may induce or exacerbate the autoimmune condition; however, VKH disease is a very rare complication associated with interferon therapy in chronic hepatitis C. We report a case of VKH disease occurring during pegylated interferon-α2b and ribavirin combination therapy for chronic hepatitis C.

A case of pedunculated hepatic hemangioma mimicking submucosal tumor of the stomach

Fri, 25 Mar 2011 00:00:01 +0100
Hepatic hemangioma is the most common benign tumor of the liver. Most such hemangiomas are small, asymptomatic, and have an excellent prognosis. Giant hepatic hemangioma has been reported in the literature, but the exophytic and pedunculated forms of hepatic hemangioma are rare. A 56-year-old woman was referred to our hospital under the suspicion of having a gastric submucosal tumor. Abdominal computer tomography (CT) scans showed a pedunculated mass from the left lateral segment of the liver into the gastric fundus, exhibiting the atypical CT findings of hepatic hemangioma. We therefore decided to perform laparoscopic resection based on the symptoms, relatively large diameter, inability to exclude malignancy, and risk of rupture of the exophytic lesion. The pathology indicated it to be a cavernous hemangioma of the liver. Herein we report a case of pedunculated hepatic hemangioma mimicking a submucosal tumor of the stomach due to extrinsic compression of the gastric fundus.

Three cases of amoebic liver abscess causing inferior vena cava obstruction, with a review of ...

Anil K Sarda, Rakesh Mittal, Baljeet K Basra, Anurag Mishra, Nikhil Talwar — Fri, 25 Mar 2011 00:00:01 +0100
Amoebic liver abscess is a common disease, especially in endemic areas, but it is a rare cause of inferior vena cava (IVC) obstruction, with only a few cases appearing in the literature. We report three cases of amoebic liver abscess complicated with obstruction of the IVC and which responded to conservative treatment or radiological intervention.

IgG4-related sclerosing cholangitis: liver biopsy findings

Han Suk Ryu, Haeryoung Kim — Fri, 25 Mar 2011 00:00:01 +0100
.

Hepatic amyloidosis

Yong Moon Shin — Fri, 25 Mar 2011 00:00:01 +0100
.

Durability of a sustained virologic response in patients with chronic hepatitis C treated with ...

Kyung-Ah Kim — Fri, 25 Mar 2011 00:00:01 +0100
.

Hemodynamic alterations in cirrhosis and portal hypertension

Moon Young Kim, Soon Koo Baik, Samuel S. Lee — Sat, 25 Dec 2010 00:00:01 +0100
Portal hypertension (PHT) is associated with hemodynamic changes in intrahepatic, systemic, and portosystemic collateral circulation. Increased intrahepatic resistance and hyperdynamic circulatory alterations with expansion of collateral circulation play a central role in the pathogenesis of PHT. PHT is also characterized by changes in vascular structure, termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the formation of new blood vessels, also occurs with PHT related in particular to the expansion of portosystemic collateral circulation. The complementary processes of vasoreactivity, vascular remodeling, and angiogenesis represent important targets for the treatment of portal hypertension. Systemic and splanchnic vasodilatation can induce hyperdynamic circulation which is related with multi-organ failure such as hepatorenal syndrome and cirrhotic cadiomyopathy.

Which treatment modality should we choose for advanced hepatocellular carcinoma?

Do Young Kim — Sat, 25 Dec 2010 00:00:01 +0100

See Article on Page 355

The definition of ‘advanced’ hepatocellular carcinoma (HCC) has been vague and included various stages. This term has sometimes meant ‘multinodular/unresectable HCC’, ‘HCC with vascular invasion’, or ‘HCC with extra-hepatic spread’. Since the introduction of the Barcelona Clinic Liver Cancer (BCLC) stage in 1999, the term ‘advanced HCC’ has been defined as a symptomatic tumor and/or invasive tumoral pattern (vascular invasion/ extrahepatic spread).¹ Based on data suggesting limited efficacy of cytotoxic systemic chemotherapy and results from the SHARP trial,^2,3 sorafenib, a multi-kinase inhibitor, is now the only drug which has been shown to prolong the survival of patients with HCC with vascular invasion or metastasis. Transarterial chemoembolization (TACE) is the standard of care for patients with multinodular HCC.⁴ Although there is not a standardized procedure with different embolic or chemotherapeutic agents, different arterial selectivity before embolization, or different schedules and indications for repeated sessions,⁵ TACE has been shown to be effective in prolonging survival compared to supportive care in randomized controlled trials and meta-analyses.^5,6 However, the outcomes of TACE depend upon patient selection. In a randomized trial which recruited HCC patients with compensatory cirrhosis, good performance status, and large or multinodular HCC with neither portal vein invasion nor distant metastasis, the 2-year survival rate was 63% compared to 27% for the untreated control group (P=0.009).⁷ In another randomized trial, inclusion of patients with symptoms or limited portal vein invasion resulted in a 2-year survival rate of 31%.⁶ In a subgroup analysis, TACE offered no survival benefit in patients with portal vein invasion. In addition to high rates of tumor recurrence or progression after the procedure, TACE promotes vascular endothelial growth factor (VEGF) production and subsequent angiogenesis. Therefore, apart from adverse events, the suboptimal anti-cancer effects of TACE observed when treating HCC with portal vein invasion may increase the chance of intra- or extra-hepatic spread of HCC. Hepatic arterial infusional chemotherapy (HAIC) using lowor high-dose 5-FU and cisplatin for unresectable HCC has been established as a treatment option in Japan and several centers in South Korea. Despite several problems associated with HAIC such as subcutaneous port implantation and catheter placement, infection, and hepatic arterial occlusion with repeated therapies, promising HAIC anti-tumor effects without significant systemic adverse events have been reported in locally advanced HCC.^8,9 In a Japanese study, low doses of 5-FU (170 mg/m² on day 1-5) and low doses of cisplatin (7 mg/m² on day 1-5) were infused through a subcutaneously-implanted port in HCC patients with portal vein thrombosis.⁸ After four courses of monthly HAIC, 4 (8.3%) and 19 (39.6%) out of 48 patients achieved complete response and partial response, respectively. In a Korean study in which high dose of 5-FU (500 mg/m² on day 1-3) and cisplatin (60 mg/m² on day) were administered, 9 (22.0%) and 14 (34.1%) patients exhibited a partial response and stable disease, respectively, without significant adverse events. The overall survival time was significantly longer in the disease-controlled group than in the disease-progression group (median of 14 versus 6 months, P <0.001).¹⁰ There seems to be no difference in 354 The Korean Journal of Hepatology Vol. 16. No. 4, December 2010 terms of efficacy between high- and low-dose regimens. A recent South Korean multicenter, randomized study showed that there was no significant difference in overall survival time (median of 193 versus 153 days, P=0.108), although the objective response rate was improved in the high-dose group compared to the low-dose group (16.7% versus 0%, P=0.024).¹¹ The presence of portal vein invasion without extra-hepatic spread is a clinical condition shared by repeated HAIC and systemic therapy using sorafenib. However, at present HAIC may not be generally recommended for treating advanced HCC because there has no randomized controlled study which shows a survival benefit of HAIC compared to sorafenib. Which transarterial therapy, then, is better for treating advanced HCC? A recent paper published by Kim et al. in The Korean Journal of Hepatology compared the treatment outcomes between high-dose HAIC and TACE in cases of advanced HCC.¹² Thirty-six patients in HAIC group had been recruited for another multi-center, prospective trial and 31 patients in TACE group were retrospectively selected from database of one institute. In this study, the objective responses (complete and partial responses) were significantly better in the group that underwent high-dose HAIC than in patients who received TACE (16.7% versus 0%, P=0.046). Overall survival was also better in the HAIC group compared to the TACE group (median survival times, 193 versus 87 days, P=0.028). The authors conclude that high-dose HAIC resulted in a better tumor response and survival outcome compared to conventional TACE using doxorubicin. Strictly speaking, TACE and HAIC have different implications. Only selected cases of HCC with portal vein invasion are amenable to TACE. On the contrary, HAIC had been developed for treating more advanced HCCs, such as cases with diffuse involvement of both lobes or main portal vein invasion, which cannot be treated with TACE. Despite retrospective matching of tumor characteristics, it is unclear how many patients had infiltrative HCC, bilobar involvement, and main portal vein invasion in each group. Furthermore, since it appeared that gelfoam embolization had not been performed universally in the TACE group, actual comparison of HAIC and TACE in treating advanced HCC under the same tumor conditions might not have been done. An important point of this study is that the effect of TACE monotherapy is a sub-optimal therapy for HCC with a substantial tumor burden, and so TACE is not beneficial in extensive (or diffusely involved) cases of HCC with or without portal vein invasion. For therapies for advanced HCC, we are armed with more treatment modalities than before. Besides HAIC, the efficacy of multimodal approaches with external beam radiation therapy, internal radiation with Yttrium-90, and combination therapies using sorafenib and other treatments for advanced HCC need to be validated by well-designed studies.^13,14

A comparative study of high-dose hepatic arterial infusion chemotherapy and transarterial ...

Sat, 25 Dec 2010 00:00:01 +0100
Background/Aims: Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC. Methods: The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks. Results: Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group. Conclusions: High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.

Prevalence of IgG anti-HAV in patients with chronic hepatitis B and in the general healthy ...

Sat, 25 Dec 2010 00:00:01 +0100
Background/Aims: Few studies have investigated hepatitis A virus (HAV) seroepidemiology in Koreans with chronic liver disease (CLD). This study compared the prevalence of IgG anti-HAV between the general healthy population and patients with hepatitis B virus-related CLD (HBV-CLD), with the aim of identifying predictors of HAV prior exposure. Methods: In total, 1,319 patients were recruited between June 2008 and April 2010. All patients were tested for IgG anti-HAV, hepatitis B surface antigen (HBsAg), and antibodies to hepatitis C virus. The patients were divided into the general healthy population group and the HBV-CLD group based on the presence of HBsAg. The seroprevalence of IgG anti-HAV was compared between these two groups. Results: The age-standardized seroprevalence rates of IgG anti-HAV in the general healthy population and patients with HBV-CLD were 52.5% and 49.1%, respectively. The age-stratified IgG anti-HAV seroprevalence rates for ages ≤19, 20-29, 30-39, 40-49, 50-59, and ≥60 years were 14.3%, 11.2%, 45.5%, 90.5%, 97.6% and 98.3%, respectively, in the general healthy population, and 0%, 9.8%, 46.3%, 91.1%, 97.7%, and 100% in the HBV-CLD group. In multivariate analysis, age (<30 vs. 30-59 years: OR=19.339, 95% CI=12.504-29.911, P<0.001; <30 vs. ≥60 years: OR=1060.5, 95% CI=142.233-7907.964, P<0.001) and advanced status of HBV-CLD (OR=19.180, 95% CI=4.550-80.856, P<0.001) were independent predictors of HAV prior exposure. Conclusions: The seroprevalence of IgG anti-HAV did not differ significantly between the general-healthy-population and HBV-CLD groups. An HAV vaccination strategy might be warranted in people younger than 35 years, especially in patients with HBV-CLD.

Prediction of compensated liver cirrhosis by ultrasonography and routine blood tests in ...

Sat, 25 Dec 2010 00:00:01 +0100
Background/Aims: Liver biopsy is a standard method for diagnosis of liver cirrhosis in patients with chronic hepatitis. Because liver biopsy is an invasive method, non-invasive methods have been used for diagnosis of compensated liver cirrhosis in patients with chronic hepatitis. The current study was designed to evaluate the usefulness of ultrasonography and routine blood tests for diagnosis of compensated liver cirrhosis in patients with chronic viral hepatitis. Methods: Two hundred three patients with chronic viral hepatitis who underwent liver biopsy were included in this study and ultrasonography and routine blood tests were analyzed retrospectively. Ultrasonographic findings, including surface nodularity, parenchyma echogenecity, and spleen size, were evaluated. The diagnostic accuracy of ultrasonography and routine blood tests were examined. Results: Discriminant analysis with forward stepwise selection of variables showed that liver surface nodularity, platelet count, and albumin level were independently associated with compensated liver cirrhosis (p<0.05). Cross-tabulation revealed that the following 4 variables had >95% specificity: platelet count <100,000 /uL; albumin level <3.5 g/dL; INR >1.3; and surface nodularity. If at least one of the four variables exists in a patient with chronic viral hepatitis, we can predict liver cirrhosis with 90% specificity and 61% sensitivity. Conclusions: These results suggest that four variables (platelet count <100,000 /uL, albumin level <3.5 g/dL, INR >1.3, and surface nodularity) can be used for identification of liver cirrhosis in patients with chronic viral hepatitis with high specificity.

Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis

Sat, 25 Dec 2010 00:00:01 +0100
Background/Aims: The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the β-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). Methods: Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 μg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. Results: A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. Conclusions: Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the β-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis.

Long-term outcome of preoperative transarterial chemoembolization and hepatic resection in ...

Sat, 25 Dec 2010 00:00:01 +0100
Background/Aims: Transarterial chemoembolization (TACE) improves the survival of patients with unresectable hepatocellular carcinoma (HCC) and has been recommended as a first-line therapy for nonsurgical patients with large or multifocal HCC. The long-term outcome of HCC patients receiving TACE prior to hepatic resection is uncertain. Methods: Between January 1997 and December 2007, 1,530 patients underwent hepatic resection for HCC at our center. Thirty-two patients received 1~12 sessions of TACE followed by surgical resection (TACE-surgery group). Their overall and recurrence-free survival rates were compared with those of 64 age- and sex-matched controls who underwent surgery only (surgery group). Overall and recurrence-free survival rates were analyzed. Results: The 1-, 2-, and 5-year overall survival rates did not differ significantly between the TACE-surgery group and the surgery group (78%, 60%, and 26%, respectively, vs. 97%, 83%, and 45%, respectively; P=0.11); however, the 1-, 2-, and 5-year recurrence-free survival rates were significantly lower in the TACE-surgery group than in the surgery group (58%, 36%, and 7%, respectively, vs. 77%, 58%, and 32%, respectively; P=0.01). The distribution of recurrence sites in the TACE-surgery group were intrahepatic in 85.7% and extrahepatic in 14.3%, and did not differ from those in the surgery group (91.4% and 8.6%, respectively; P=0.66). Conclusions: HCC patients who underwent TACE before resection appear to have overall survival rates that are comparable to those without preoperative therapy, although recurrence rates appear to be higher in patients with TACE.

Validation of P2/MS for reflecting hepatic fibrosis in patients with hepatocellular carcinoma

Sat, 25 Dec 2010 00:00:01 +0100
Background/Aims: P2/MS is known as a simple, accurate, and noninvasive marker for determination of the degree of hepatic fibrosis in patients with viral hepatitis. We aimed to validate P2/MS in patients with HCC. Methods: Consecutive HCC patients who underwent surgical resection between June 2007 and March 2009 at Seoul National University Hospital were enrolled. Fibrosis stage was reviewed and assessed according to METAVIR scoring. P2/MS values [platelet count (109/L)]2/ [monocyte fraction (%)×segmented neutrophil fraction (%)] and other noninvasive fibrosis scoring systems were calculated. Results: A total of 171 patients were included; seven patients with METAVIR F1, 31 with F2, 41 with F3, and 92 with F4. The area under the receiver-operating characteristic curve of P2/MS was 0.804 [95% confidence interval (CI), 0.681~0.927] for detection of significant fibrosis (F2-F4) and 0.769 (95% CI, 0.698~0.839) for detection of histological cirrhosis (F4). At a value < 62, P2/MS detected significant fibrosis with a specificity of 85.7% (95% CI, 42.0~99.2) and a positive likelihood ratio of 4.268 (95% CI, 0.692~26.309); and at a value > 115, P2/MS ruled out significant fibrosis with a sensitivity of 90.2% (95% CI, 84.4~94.1) and a negative likelihood ratio of 0.34 (95% CI, 0.106~0.095). P2/MS had a superior efficacy for detection of hepatic fibrosis in patients with HCC compared to the other noninvasive panels. Conclusions: P2/MS can accurately detect fibrosis in patients with HCC. Thus, P2/MS might be utilized as a noninvasive index reflecting the degree of hepatic fibrosis in HCC patients.

Sigmoid colon metastasis from hepatocellular carcinoma

Sat, 25 Dec 2010 00:00:01 +0100
Hepatocellular carcinoma (HCC) is a major health problem worldwide, and it has a poor prognosis. Extrahepatic metastasis from HCC is not unusual, with direct invasion representing the main spreading mode. Sites that are frequently involved are the lung, bone, and lymph nodes. There are few reports of HCC invading the distant gastrointestinal tract, especially hematogenously. Herein we report a case of sigmoid colon metastasis from HCC. The patient was diagnosed with HCC and treated with transcatheter arterial chemoembolization (TACE). Eighteen months after TACE the patient presented with abdominal pain on the left lower quadrant, and a CT scan showed an enhanced mass on the sigmoid colon. Immunohistochemical staining revealed that a tumor cell was positive for polyclonal carcinoembryonic antigen and weakly positive for hepatocyte antigen, supporting the diagnosis of HCC metastasis. The patient underwent anterior resection for the metastatic HCC.

Hepatogastric fistula caused by direct invasion of hepatocellular carcinoma after transarterial ...

Sat, 25 Dec 2010 00:00:01 +0100
A 63-year-old man with a history of hepatitis-B-related hepatocellular carcinoma (HCC) in the left lateral portion of the liver received repeated transcatheter arterial chemoembolization (TACE) and salvage radiotherapy. Two months after completing radiotherapy, he presented with dysphagia, epigastric pain, and a protruding abdominal mass. Computed tomography showed that the bulging mass was directly invading the adjacent stomach. Endoscopy revealed a fistula from the HCC invading the stomach. Although the size of the mass had decreased with the drainage through the fistula, and his symptoms had gradually improved, he died of cancer-related bleeding and hepatic failure. This represents a case in which an HCC invaded the stomach and caused a hepatogastric fistula after repeated TACE and salvage radiotherapy.

A case of hepatocellular carcinoma in the caudate lobe successfully treated by transcatheter ...

Sat, 25 Dec 2010 00:00:01 +0100
Hepatocellular carcinoma (HCC) in the caudate lobe remains one of the most intricate locations where various treatments tend to pose problems with regard to the optimal approach. Surgical resection has been regarded as the most effective treatment; however, isolated resection of the caudate lobe is strenuous and associated with a high rate of early recurrence. Percutaneous ablation might be technically difficult or impossible to perform due to the deep location of tumors and adjacent large vessels. Treatment with drug-eluting beads (DEB) can potentially enhance the therapeutic efficacy for patients with unresectable HCC by drawing on the slower, more consistent drug delivery process. We described a case of a 62-year-old man with HCC in the caudate lobe who was successfully treated by DEB.

Sclerosed hemangioma of the liver

So-Young Jin — Sat, 25 Dec 2010 00:00:01 +0100
.

Focal nodular hyperplasia: with a focus on contrast enhanced ultrasound

Ho Suk Kang, Byung Kook Kim, Chan Sup Shim — Sat, 25 Dec 2010 00:00:01 +0100
.

The effect of sorafenib on hepatic stellate cells: implication of its effect on tumor ...

Jung Il Lee — Sat, 25 Dec 2010 00:00:01 +0100
.

New treatments for chronic hepatitis C

Jae Young Jang, Raymond T. Chung — Sat, 25 Sep 2010 00:00:01 +0100
Treatments for chronic hepatitis C has evolved significantly in the past 15 years. The standard of care (SOC) is peginterferon alfa-2a/-2b with ribavirin for 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively. The treatment duration can be individualized based on the baseline viral load and the speed of the virologic response during treatment. However, current therapies are associated with side effects, complications, and poor patient tolerability. Therefore, there is an urgent need to identify better strategies for treating this disease. An improved sustained virologic response (SVR) can be achieved with new HCV-specific inhibitors against NS3/4A and NS5B polymerases. Recent trials have found SVR rates in patients with HCV genotype 1 infection of 61~68% and 67~75% for combining the SOC with the protease inhibitors telaprevir and boceprevir, respectively. Several new HCV-specific inhibitors such as protease inhibitors and nucleoside and non-nucleoside polymerase inhibitors as well as non-HCV-specific compounds with anti-HCV activity are currently in clinical evaluation. In this review we discuss these new treatments for chronic hepatitis C.

Hypoxia-inducible factor 1, hepatocellular carcinoma and angiogenesis

Jin-Wook Kim — Sat, 25 Sep 2010 00:00:01 +0100

See Article on Page 280

Angiogenesis is essential for tumor growth,¹ and it has been shown that anti-angiogenic therapy has been proven to be effective in several cancers such as colorectal cancer^2,3 and hepatocellular carcinoma (HCC).⁴ Currently available antiangiogenic cancer chemotherapy targets the vascular endothelial growth factor (VEGF) pathway by VEGF monoclonal antibody (bevacizumab)³ or multi-targeted receptor tyrosine kinase inhibitors (sorafenib).⁴ Hypoxia-inducible factor 1 (HIF-1) is a heterodimer protein which is composed of oxygen-regulated HIF-1α subunit and constitutively expressed HIF-1β subunit.^5,6 Under normoxic condition, the degradation of HIF-1α subunit is facilitated by ubiquitination following the hydroxylation of proline residue(s). However, under hypoxic condition, stability of HIF-1α increases due to suppressed proline hydroxylation, leading to increased transcription of genes associated with adaptive homeostatic response to hypoxia such as erythropoiesis, glucose metabolism and angiogenesis.⁷ In addition to intratumoral hypoxia, loss of function of tumor-suppressor genes also contributes to over-expression of HIF-1α in various human cancers.⁶ HIF-1 is a key regulatory factor for angiogenesis in response to hypoxia: it induces expression of angiogenic growth factors such as VEGF, stromal derived factor 1, angiopoietin 2, placental growth factor, platelet-derived growth factor B and stem cell factor.⁸ Many human cancers over-express HIF-1α, and expression of HIF-1α is associated with poor prognosis.^6,9 In hepatitis B virus-associated HCC, high expression of HIF-1α is found in half of tumor specimens and correlated with venous invasion and lymph node invasion.¹⁰ These findings suggest the possibility of HIF-1α as a novel therapeutic target in HCC. In the current issue, Choi et al. suppressed HIF-1α by adenovirus-mediated small hairpin RNA and observed that proliferation of hepatoma cell lines was suppressed and the new vessel formation by vascular endothelial cells was inhibited.¹¹ This suppressive effect against hepatoma cells is concordant with the report by WeiXing et al. which knocked down HIF-1α by antisense oligonucleotide.¹² In the current study, however, the mechanisms by which HIF-1α directly inhibits the proliferation of hepatoma cell lines were not examined. In hypoxic state, HIF-1 can either induce or inhibit apoptosis.¹³ Moreover, a recent report shows that knock-down of HIF-1α causes reciprocal increase of HIF-2α and vice versa, leading to attenuated apoptosis in HepG2 cells.¹⁴ Therefore, further studies are warranted to examine the effects of HIF-1α on the apoptosis and proliferation of HCC in hypoxic state. Recent reports including this study by Choi et al. have demonstrated that knock-down of HIF-1α by small interfering RNA¹⁵ or short hairpin RNA can disrupt angiogenesis by HUVEC cells. However, the therapeutic potential of anti-angiogenic effect by targeting HIF-1 needs to be further validated in animal HCC models. One recent study targeting HIF-1α showed suppressed tumor growth and microvessel density in a murine subcutaneous HCC model.¹⁶ However, two reports assessing the effect of HIF-1α on the tumor growth in orthotopic hepatoma models showed conflicting results.^17,18 These results imply that the action of HIF-1 may be influenced by the types of tumor cells and/or the stromal components of the tumor.⁹ Further animal studies are also warranted to examine the efficacy of combination therapy that includes HIF-1α targeting and conventional types of anti-cancer drugs.

Effects of the knockdown of hypoxia inducible factor-1

Sat, 25 Sep 2010 00:00:01 +0100
Background/Aims: Hypoxia-inducible factor-1α (HIF-1α) is a central transcriptional factor involved in the cellular responses related to various aspects of cancer biology, including proliferation, survival, and angiogenesis, and the metabolism of the extracellular matrix in hypoxia. This study evaluated whether adenovirus-mediated small hairpin RNA (shRNA) against HIF-1α (shHIF-1α) inhibits cell proliferation and angiogenesis in hepatocellular carcinoma (HCC) cell lines. Methods: Knockdown of HIF-1α expression was constructed by adenovirus-mediated RNA interference tools, and HCC cell lines infected with shHIF-1α coding virus were cultured under a hypoxia condition (1% O₂) for 24 hours. Following infection, the expression levels of HIF-1α, angiogenesis factors, and matrix metalloproteinase (MMP) were examined using Western blotting. Cell proliferation and angiogenesis were measured by a cell proliferation assay (MTT assay) and an angiogenesis-related assay (invasion and tube-formation assay), respectively. Results: Adenovirus mediated inhibition of HIF-1α induced suppression of tumor growth in HCC cell lines. It also down-regulated the expression of angiogenesis factor and MMP proteins. Angiogenesis as well as mobility of vascular cells to tumor was suppressed by adenovirus-mediated shHIF-1α-infected groups in human umbilical vein endothelial cells (HUVECs). Conclusions: These data suggest that adenovirus-mediated inhibition of HIF-1α inhibits the invasion, tube formation, and cell growth in HUVECs and HCC cells.

Serum prohepcidin levels in chronic hepatitis C, alcoholic liver disease, and nonalcoholic ...

Sat, 25 Sep 2010 00:00:01 +0100
Background/Aims: Patients with various chronic liver diseases frequently have increased body iron stores. Prohepcidin is an easily measurable precursor of hepcidin, which is a key regulator of iron homeostasis. This study investigated the serum prohepcidin levels in patients with various chronic liver diseases with various etiologies. Methods: Serum prohepcidin levels were measured in patients with chronic hepatitis C (CH-C) (n=28), nonalcoholic fatty liver disease (NAFLD) (n=24), and alcoholic liver disease (ALD) (n=22), and in healthy controls (n=25) using commercial ELISA. Serum interleukin 6 (IL-6) levels and blood iron indices were also measured. Results: The serum levels of both prohepcidin and IL-6 were significantly higher in CH-C patients than in healthy controls, and there was a positive correlation between the IL-6 and prohepcidin levels (r =0.505, p=0.020). The prohepcidin levels in ALD patients did not differ from those in controls, despite their significantly elevated IL-6 levels. There was a tendency for a negative correlation between serum prohepcidin levels and transferrin saturation in ALD patients (r =-0.420, p=0.051). Neither prohepcidin nor IL-6 was significantly elevated in the NAFLD group, despite the presence of elevated serum iron and ferritin levels. Conclusions: The role of prohepcidin may differ in different human liver diseases. In the setting of CH-C, both the serum prohepcidin and IL-6 levels were significantly elevated and were positively correlated with each other.

Factors influencing the severity of acute viral hepatitis A

Sat, 25 Sep 2010 00:00:01 +0100
Background/Aims: Most patients with acute viral hepatitis A have a favorable course, but a few of them suffer from severe forms of hepatitis such as fulminant hepatitis. This study was carried out to identify the factors influencing the severity of acute viral hepatitis A. Methods: We retrospectively reviewed the medical records of 713 patients with acute hepatitis A, who were divided into two groups: severe hepatitis A (N=87) and non-severe hepatitis A (N=626). Severe hepatitis was defined as fulminant hepatitis or prolongation of prothrombin time (INR≥1.5). Clinical variables were compared between the two groups. Results: The incidence of fulminant hepatitis was 1.4 % (10/713) in patients with acute hepatitis A. Thirty-three (4.6 %) cases exhibited HBsAg positivity. In multivariate analyses, significant alcohol intake and the presence of HBsAg were significant predictive factors of fulminant hepatitis A, and significant alcohol intake and age were significant predictive factors of severe hepatitis A. HBeAg and HBV-DNA status did not affect the clinical course of hepatitis A in chronic hepatitis B carriers. Conclusions: While most patients with acute hepatitis A have an uncomplicated clinical course, our data suggest that a more-severe clinical course is correlated with being older, significant alcohol intake, and chronic hepatitis-B-virus infection.

Diagnostic value of cystatin C for predicting acute kidney injury in patients with liver cirrhosis

Mi Yeon Chung, Dae Won Jun, Su Ah Sung — Sat, 25 Sep 2010 00:00:01 +0100
Background/Aims: The present study aimed to determine the role of cystatin C as a prognostic factor for acute kidney injury and survival in cirrhotic patients. Methods: The study investigated 53 liver cirrhosis patients. The renal function was evaluated by serum creatinine, serum and urine cystatin C, and 24-hour creatinine clearance on admission. Acute kidney injury was defined as a serum creatinine level exceeding the normal range (>1.2 mg/dl) and an increase of at least 50% from the baseline value. Multivariate analysis, receiver operating characteristic curve, and survival analysis were used to investigate prognostic factors for acute kidney injury and survival. Results: Nine of the 53 cirrhotic patients (17.0%) developed acute kidney injury within 3 months. Both serum creatinine and cystatin C were predictive factors for acute kidney injury in univariate analysis, with a diagnostic accuracy of 0.735 (95% confidence interval (CI), 0.525-0.945; p=0.028) for serum cystatin C and 0.698 (95% CI, 0.495-0.901, p=0.063) for creatinine. In multivariate analysis, only serum cystatin C was an independent risk factor for acute kidney injury. The sensitivity and specificity of a serum cystatin C level of >1.23 mg/L to acute kidney injury were 66% and 86%, respectively. Serum cystatin C was positively correlated with the Model for End-Stage Liver Disease (MELD) and MELD-Na scores (r=0.346 and p=0.011, and r=0.427 and p=0.001, respectively). Comparison of the survival rates over the observation period revealed that a serum cystatin C level of >1.23 mg/L was a useful marker for short-term mortality (p<0.001). Conclusions: The accuracy in predicting acute kidney injury and short-term mortality was higher for a serum cystatin C level of >1.23 mg/L than for the serum creatinine concentration in patients with cirrhosis.

Effect of alcohol on the development of hepatocellular carcinoma in patients with hepatitis B ...

Sat, 25 Sep 2010 00:00:01 +0100
Background/Aims: Whether alcohol intake increases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection remains controversial. The aim of this study was to determine the effect of alcohol intake on the development of HCC. Methods: Between January 2006 and August 2008, 146 patients with an initial diagnosis of HCC who were hospitalized in 3 major hospitals in the Incheon area were enrolled as cases. Another 146 cirrhotic patients, who matched the cases by age and sex, were enrolled as controls. All cases and controls were HBsAg positive, and had a history of lifetime alcohol intake. Results: The cases and controls were aged 53±8 and 53±9 years (mean±SD), respectively, with each group comprising 118 males and 28 females. The basal laboratory data, distribution of Child-Pugh class, HBeAg positivity (31.5% vs. 37.7%), HBV DNA level (5.74±2.35 vs. 5.98±2.29 log10 copies/mL), and proportion with a lifetime alcohol intake of more than 292 kg (30.8% vs. 34.9%) did not differ between cases and controls. The cumulative alcohol intake and the proportion of heavy drinkers did not differ between the two groups in male patients. Conclusions: Alcohol intake might not increase the risk of HCC in patients with HBV infection.

Forty-eight weeks treatment with clevudine 30 mg qd versus lamivudine 100 mg qd for chronic ...

George KK Lau, Nancy Leung — Sat, 25 Sep 2010 00:00:01 +0100
Background/Aims: Clevudine is a pyrimidine analogue with potent activity against hepatitis B virus (HBV) replication in vitro. In a previous pivotal phase III clinical study, 24 weeks treatment with clevudine 30 mg has been shown to profoundly suppress HBV replication and normalize serum alanine aminotransferase level. Methods: In this study, we compare the efficacy and safety of clevudine (30 mg daily) versus lamivudine (100 mg daily) for 48 weeks in treatment-naive chronic hepatitis B e antigen (HBeAg) positive patients. Results: Ninety-two chronic HBeAg positive patients were randomized to receive clevudine 30 mg daily or lamivudine 100 mg daily in a 1:1 ratio. The clevudine group demonstrated greater viral suppression at week 48 when compared with the lamivudine group (median reduction: 4.27 vs. 3.17 log10 copies/ml at week 48, p<0.0001). At week 48, serum HBV DNA level was below 300 copies/mL in 73% and 40% in the clevudine and lamivudine groups, respectively (p=0.001). HBeAg seroconversion occurred in 18% of patients in the clevudine group versus 12% in the lamivudine group at week 48. Lamivudine-resistant mutations were detected in 11 (24%) patients in the lamivudine group, who showed viral rebound during lamivudine therapy but no resistance was found in the clevudine group during 48-week treatment period. Conclusions: A 48-week dosing with clevudine 30 mg daily was superior to lamivudine 100 mg daily in suppressing HBV replication, with no emergence of viral breakthrough in patients with HBeAg positive chronic hepatits B.

A case of concomitant Gilbert

Sat, 25 Sep 2010 00:00:01 +0100
We describe moderate hyperbilirubinemia in a 28-year-old man who suffered from gallstones and splenomegaly, with combined disorders of hereditary spherocytosis (HS) and Gilbert’s syndrome (GS). Since it is difficult to diagnose HS in the absence of signs of anemia, we evaluated both the genetic mutation in the UGT1A1 gene and abnormalities in the erythrocyte membrane protein; the former was heterozygous for a UGT1A1 allele with three mutations and the latter was partially deficient in ankyrin expression. This is the first report of the concomitance of HS and GS with three heterozygous mutations [T-3279G, A (TA)7TAA, and G211A] in the UGT1A1 gene.

Detection of distant metastasis to skeletal muscle by 18F-FDG-PET in a case of intrahepatic ...

Sat, 25 Sep 2010 00:00:01 +0100
Intrahepatic cholangiocarcinoma is a rare malignancy that originates from the epithelial cells of the intrahepatic bile ducts. Intrahepatic cholangiocarcinoma can metastasize in lymphatic chains, including the hepatoduodenal ligament, and it often invades adjacent organs or metastasizes to other visceral organs such as the lungs, bones, adrenal glands, and brain. However, distant skeletal muscle metastasis is very rare. Moreover, a metastatic skeletal muscle tumor rarely shows specific symptoms, making it difficult to identify in a routine examination. A 45-year-old man with a chief complaint of right upper quadrant abdominal pain was admitted to our hospital. Abdominal ultrasound and computed tomography with contrast enhancement showed a malignant mass in the right hepatic lobe, and 2-[¹⁸F] fluoro-2-deoxy-D-glucose positron-emission tomography revealed distant skeletal muscle metastases in the thorax and buttock. The patient underwent an ultrasound-guided percutaneous needle biopsy for the metastatic low-echo masses in the skeletal muscle.

Clinical courses after administration of oral corticosteroids in patients with severely ...

Sat, 25 Sep 2010 00:00:01 +0100
Acute hepatitis A is currently outbreaking in Korea. Although prognosis of acute hepatitis A is generally favorable, a minority of patients are accompanied by fatal complications. Severe cholestasis is one of the important causes of prolonged hospitalization in patients with acute hepatitis A. In such cases, higher chances of additional complications and increased medical costs are inevitable. We report three cases of severely cholestatic hepatitis A, who showed favorable responses to oral corticosteroids. Thirty milligram of prednisolone was initiated and tapered according to the responses. Rapid improvement was observed in all cases without side effects. We suggest that corticosteroid administration can be useful in hepatitis A patients with severe cholestasis who do not show improvement by conservative managements. Clinical trial will be needed to evaluate effectiveness of corticosteroids in these patients.

Massive hepatic necrosis with large regenerative nodules

Haeryoung Kim, Young Nyun Park — Sat, 25 Sep 2010 00:00:01 +0100
.

Hepatic adrenal rest tumor mimicking hepatocellular carcinoma

Yong Moon Shin — Sat, 25 Sep 2010 00:00:01 +0100
.

Growing attention to an old marker, hepatitis B surface antigen, in the natural history of ...

Jeong Won Jang — Sat, 25 Sep 2010 00:00:01 +0100
.

Prognosis of Korean patients with primary biLiary cirrhosis

Byung-Cheol Song, M.D. — Sat, 01 Jan 2000 00:00:01 +0100
.

Pro-apoptotic function of hepatitis B virus X protein

Kyun-Hwan Kim, Ph.D.
Infection of hepatitis B virus (HBV) is a main cause of liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Among the HBV-encoded proteins, the HBV X protein (HBx) has been suspected to be strongly involved in HBV-associated liver pathogenesis. HBx, a virally encoded multifunctional regulator, has been shown to induce apoptosis, anti-apoptosis, proliferation, and transformation of cells depending on the cell lines, model systems used, assay protocols, and research groups. Among the several activities of HBx, the pro-apoptotic function of HBx will be discussed in this review. Given that the disruption of apoptosis pathway by HBx contributes to the liver pathogenesis, a better understanding of the molecular interference in the cellular pro-apoptotic networks by HBx will provide useful clues for the intervention in HBV-mediated liver diseases.

Clinical factors influencing Liver stiffness as measured by transient elastography ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Transient elastography as performed using the FibroscanⓇ is a useful noninvasive method for evaluating hepatic fibrosis. However, recent studies have found that liver stiffness measurement (lSM) values are inappropriately elevated in acute hepatitis or in the acute flare state of chronic hepatitis, suggesting that the lSM value obtained by the FibroscanⓇ is not a reliable marker for fibrosis. We retrospectively evaluated the clinical factors influencing the lSM value obtained using transient elastography as performed using the FibroscanⓇ in patients with chronic liver disease. Methods: A total of 298 patients who were followed in Kungpook National University Hospital from November 2007 to May 2008 due to previously established liver cirrhosis or chronic liver disease were investigated using the FibroscanⓇ, laboratory test, ultrasound, and/or abdominal computed tomography. Results: The 298 patients were aged 47.8±12.9 years (mean±SD). The cut-off value for a diagnosis of liver cirrhosis was 12.5 kPa (as used in previous studies). Thirty-six patients (15%) and 202 patients (85%) with chronic liver disease without clinical manifestation of cirrhosis had lSMs of >12.5 kPa and <12.5 kPa, respectively. Multivariate analysis revealed that lSM values were unusually increased in patients with chronic liver disease who were older (P=0.007) or who had increased gamma gultamyltranspetidase (GGT) (P=0.022), decreased albumin (P=0.015), or increased total bilirubin (P=0.009). Conclusions: This study reveals that age, GGT, and albumin are clinical factors influencing lSM values. This reinforces the need to interpret lSM values in the context of a defined diagnosis, biochemical data, radiologic examination, and other clinical findings.

Clinical features of gas-forming Liver abscesses: comparison between diabetic and nondiabetic ...
Background/Aims: Patients with diabetes mellitus (DM) are more likely to have a pyogenic liver abscess with gas formation, which is associated with higher morbidity and mortality. The morbidity and mortality in pyogenic liver abscess are also higher in DM patients than in non-DM patients. This study evaluated the morbidity, mortality, and clinical features in patients with gas-forming liver abscesses associated with DM. Methods: Among 379 cases of pyogenic liver abscess excluding malignancy from January 2001 through December 2009, 25 patients treated for pyogenic-gas-forming liver abscesses were reviewed retrospectively. We compared the morbidity, mortality, and clinical findings in patients with pyogenic-gas-forming liver abscesses between DM and non-DM patients. Results: Gas formation was present in 25 (6.6%) of 379 cases with pyogenic liver abscess. DM was combined with gas-forming liver abscesses in 19 cases (76%). The most common organism responsible for the gas formation was Klebsiella pneumoniae (82%). Complications were present in 23 cases (92%) of gas-forming liver abscesses, with pulmonary complications (especially pleural effusion) being the most common (n=14, 61%). Four patients (16%) died of sepsis. Conclusions: Gas-forming liver abscesses are not uncommon in cases of pyogenic liver abscesses and are associated with high morbidity and mortality rates. The clinical manifestations and complications do not differ significantly between DM and non-DM patients.

Clinical features and prognosis of primary biliary cirrhosis in Korea
Background/Aims: This study investigated the clinical features and prognosis of primary biliary cirrhosis (PBC) in Korea. Methods: Clinical data of patients diagnosed as PBC between 1997 and 2008 at eight referral hospitals were analyzed retrospectively. PBC was diagnosed based on liver function tests, presence of serum antimitochondrial antibody (AMA), and histopathological findings. Results: In total, 251 patients (218 females, 33 males, mean age 54 years) were enrolled, and the mean follow-up duration was 33.5 months. At the diagnosis, 61% of the patients were asymptomatic, 12% had decompensated liver cirrhosis, and 98% were positive for AMA. The serum alkaline phosphate (AlP) level was 2.6 times the upper limit of normal, aspartate aminotransferase was 105 U/l, and bilirubin was 2.0 mg/dl. The mean Mayo risk score was 5.5, and the Child-Pugh class was A, B, and C in 79%, 19%, and 2% of the patients, respectively. Ursodeoxycholic acid (UDCA) was used for treatment in 88% of the patients, among which 70% exhibited biochemical responses defined as normalization or a >40% decrease in AlP at 6 months. Eight deaths occurred during the follow-up, the causes were variceal bleeding, hepatic failure, and sepsis. The overall 5-year survival rate was 95%. The poor prognostic factors were being older than 60 years, high bilirubin, low albumin, ascites, high Mayo risk score, Child-Pugh class C, and initial presence of hepatic decompensation. Conclusions: Most patients diagnosed as PBC were asymptomatic, and these patients had a favorable short-term prognosis. The prognosis of PBC was dependent on the initial severity of liver disease.

Genotypic resistance to entecavir in chronic hepatitis B patients

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: The prevalence and clinical characteristics of entecavir (ETV) resistance is not well known. The aim of this study was to determine the frequency of genotypic resistance in nonresponders and virologic breakthrough (VBT) patients. Methods: The medical records of 76 chronic hepatitis B patients treated for a least 6 months from October 2006 to October 2008 were reviewed retrospectively. We divided patients into two groups: nucleoside analogue (NA)-na?ve patients (n=38) and lAM experienced patients (n=38). NA-na?ve and lAM experienced patients received ETV at 0.5 and 1.0 mg/day, respectively. The virologic response and VBT were investigated in both groups. We used the multiplex restriction fragment mass polymorphism (RFMP) method to test genotypic resistance at the rtI169, rtT184, rtS202, rtM204, and rtM250 sites. Results: Age, gender, serum AlT, and HBV DNA level before treatment did not differ between the groups. Neither VBT nor nonresponse was observed in the NA-na?ve group, whereas VBT and nonresponse were observed in three patients each in the lamivudine (lAM)-experienced group, all six patients had YMDD mutation at study enrollment, all three patients with VBT had genotypic resistance to ETV, but the three nonresponse patients did not have genotypic resistance to ETV. Conclusions: We suspect that VBT is mostly associated with genotypic resistance to ETV. However, nonresponse might be associated with the continuance or reselection of the YMDD mutant in lAM-experienced patients.

Mutations within the interferon sensitivity determining region in Korean patients infected with ...
Background/Aims: The treatment response to interferon could differ with mutations in the interferon-sensitivity-determining region (ISDR) in patients infected with hepatitis C virus (HCV) genotype-1b (HCV-Ib). We examined the pattern of ISDR mutations and analyzed whether the number of amino acid substitutions influences the treatment response to peginterferon plus ribavirin in chronic hepatitis or cirrhotic patients infected with HCV-Ib. Methods: The study population comprised 52 patients who visited Seoul Asan Medical Center and Seoul National University Bundang Hospital from January 2006 to December 2008 and who received peginterferon alpha-2a (n=37) or -2b (n=15) plus ribavirin, and whose serum was stored. We analyzed the early virologic response, end-of-treatment response, and sustained virologic response (SVR), and examined the ISDR using direct sequencing. Results: The proportions of patients with ISDR mutation types of wild (0mutations), intermediate (1-3 mutations), and mutant (≥4 mutations) were 50.0%, 42.3%, and 7.7%,respectively, and the corresponding SVR rates were 63%, 50%, and 67% (p>0.05). The SVR rates were 59.4% and 50.0% in patients with <2 and ≥2 mutations, respectively (p>0.05). On univariate analysis, age was the only predictive factor for SVR (p=0.016). The pretreatment HCV RNA titer tended to be lower in those with SVR, but without statistical significance (p=0.069). Conclusions: The frequency of ISDR mutations was low in our cohort of Korean patients infected with HCV-Ib. Therefore, ISDR mutations might not contribute to the response to treatment with peginterferon plus ribavirin.

Could patients who underwent hepatic resection due to hepatocellular carcinoma with high ...
Background/Aims: The follow-up strategy after hepatectomy for hepatocellular carcinoma (HCC) usually depends on the experience of physician, resulting in frequent imaging studies, which leads to increased cost. Hence, we investigated the role of monitoring alpha-fetoprotein (AFP) levels after hepatectomy in patients with preoperative high AFP. Methods: From January 2000 to December 2004, 66 patients who underwent curative hepatectomy due to HCC with preoperative AFP level >400 ng/ml were reviewed. Changes in AFP level after the operation were investigated. The recurrence was suspected in case of two consecutive increase of AFP over cut-off value. Cut-off value was determined by ROC curve. All patients were divided into 2 groups: patients who met the definition (Group S) and those who didn`t (Group D). Results: AFP level of 20ng/ml was proposed as the cut-off value for diagnosis of recurrence by ROC curve. Thirty two patients who didn`t have the AFP level decreased below 20 ng/ml after the resection had HCC recurred, whereas 16 out of 34 patients who had AFP decreased had tumor recurrence. The AFP level of patients without recurrence was kept below 20 ng/ml during the follow-up. The AFP level of 44 out of 48 recurred patients increased over 20ng/ml upon recurrence. By definition, group D were 5 patients. In 4 patients of group D, the AFP level didn`t increase above 20 ng/ml upon recurrence. These patients had HCC and they recurred 1 year after the surgery. Conclusions: In patients with preoperative AFP level >400 ng/ml, the AFP level tended to increase above 20ng/ml at recurrence mostly within 1 year. Hence, we proposed that these patients could be monitored by only AFP until 1 year after surgery.

Deficiencies in proteins C and S in a patient with idiopathic portal hypertension accompanied ...
Portal vein thrombosis (PVT) is an uncommon cause of presinusoidal portal hypertension. Among various hepatoportal disorders, noncirrhotic portal hypertension conditions such as idiopathic portal hypertension (IPH) are considered to have a close relation with PVT. PVT is known to have several predisposing conditions, including infection, malignancies, and coagulation disorders. There is growing interest and recognition that deficiencies in proteins C and S are associated with a hypercoagulable state. These deficiencies are regarded as key factors of systemic hypercoagulability and recurrent venous thromboembolism. We report the case of a 19-year-old male diagnosed as IPH with PVT and combined deficiencies in proteins C and S.

Toxic hepatitis associated with Polygoni multiflori
Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.

Occurrence of diabetic ketoacidosis and autoimmune thyroiditis in a patient treated with ...
Combined pegylated interferon and ribavirin therapy for chronic hepatitis C infection cause a wide range of side effects, including flu-like syndrome, hematological abnormalities, cardiovascular symptoms, gastrointestinal symptoms, pulmonary dysfunction, depression, and retinopathy. Interferon-alpha has been shown to be related to the development of various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, and type 1 diabetes mellitus (DM). Type 1 DM and thyroid disease respectively develop in 0.08～2.61% and 10～15% of patients treated with combined interferon-alpha and ribavirin for chronic hepatitis C. The coexistence of type 1 DM and autoimmune thyroiditis was rarely reported. We report a case of a 33-year-old female patient with chronic hepatitis C who simultaneously developed diabetic ketoacidosis and autoimmune thyroiditis after treatment with pegylated interferon-alpha 2b and ribavirin.

Infantile hemangioendothelioma with increased serum

Jae Yeon Seok, M.D., Young-Bae Kim, M.D. — Sat, 01 Jan 2000 00:00:01 +0100
.

Hepatic tuberculosis presenting as a Large Liver mass

Yong Moon Shin, M.D.
.

The Korean Joumal of Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotype ...

In Hee Kim, M.D.
Background/Aims: This randomized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 microg/wk plus ribavirin 1,000/1,200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response (VR). Methods: Patients with arapid VR (RVR, undetectable hepatitis C virus [HCV]-RNA level (<50 IU/ml at week 4) were treated for 24 weeks, those with an early VR (EVR, no RVR but undetectable HCV-RNA level or >or= 2-log(10) decrease at week 12) were randomized to 48 (group A) or 72 weeks of treatment (group B, peginterferon alfa-2a was reduced to 135 microg/wkafter week 48). Patients without an EVR continued treatment until week 72 if they had undetectable HCV-RNA levels at week 24. The primary end point was relapse, sustained VR (SVR, undetectable HCV-RNA level after 24 weeks of follow-up evaluation) was a secondary end point. Results: Of 551 genotype 1/4 patients starting treatment, 289 were randomized to group A (N=139) or group B(N=150). The relapse rate was 33.6% in group A(95% confidence interval [CI], 24.8%-43.4%) and 18.5% in group B (95% CI, 11.9%-27.6%, P=0.0115 vs group A) and the SVR rate was 51.1% (95% CI,42.5%-59.6%) and 58.6% (95% CI, 50.3%-66.6%, P>0.1), respectively. The overall SVR rate was 50.4% (278 of 551, 95% CI, 46.2%-54.7%), including 115 of 150 patients with an RVR treated for 24 weeks and 4 of 78 patients without an EVR. Conclusions: Extending therapy with peginterferon alfa-2a/ribavirin to 72 weeks decreases the probability of relapse in patients with an EVR. If they can be maintained on extended-duration therapy, SVR rates also may improve.

2010 EASl Highights : Topics related to the clinical study of hepatitis B

Moon Young Kim, M.D.
.

2010 EASl Highights : Topics related to basic research of hepatitis B

Hyung Joon Yim, M.D.
.

2010 EASl Highights : Topics related to hepatitis C

Yeon Seok Seo, M.D.
.

2010 EASl Highights : Topics related to clinical Liver cirrhosis

Oh Sang Kwon, M.D.
.

2010 EASl Highights : Topic related to Liver fibrosis and cirrhosis (Basic science)

Jin-Woo Lee, M.D., Ph.D.
.

2010 EASl Highights : Topics related to alcoholic and non-alcoholic Liver disease

Jae Youn Cheong, M.D.
.

2010 EASl Highights : Topics related to clinical hepatocellular carcinoma

Jung Hyun Kwon, M.D.
.

2010 EASl Highights : Topics related to basic researches of hepatocellular carcinoma

Ji Hoon Kim, M.D.
.

2010 EASl Highights : Topics related to Liver transplantation and surgery for hepatocellular ...

Ju Hyun Shim, M.D.
.

Predictors for virologic response in management of chronic hepatitis B

Jung Min Lee, M.D.1, Sang Hoon Ahn, M.D.1-3 — Sat, 01 Jan 2000 00:00:01 +0100

Acute Liver failure in Korea: etiology, prognosis and treatment

Young Suk Lim
Acute liver failure (ALF) is a rare condition in which rapid deterioration of liver function results in altered mentation and coagulopathy in individuals without previously recognized liver disease. The outcomes of patients with ALF vary greatly according to etiology, and the etiology of ALF varies markedly by geographical region. In Korea, about 90% of ALF are associated with etiologies that usually result in poor outcomes, including hepatitis B virus (HBV) infection and herbal remedies. The main causes of death in patients with ALF are increased intracranial pressure, systemic infection, and multi-organ failure. Recent advances in the intensive care of patients with ALF have contributed to a marked improvement in their overall survival. Emergency adult to adult living-donor liver transplantation (LDLT) can be performed expeditiously and safely for patients with ALF, and greatly improves survival rate as well as deceased-donor transplantation. As the window during which transplantation is possible is limited, emergency adult LDLT should be considered to be one of the first-line treatment options in patients with ALF, especially in regions in which ALFs are caused by etiologies associated with poor outcome and the supply of organs is very limited. (Korean J Hepatol 2010;16:5-18)

Clinical features of patients with fulminant hepatitis A requiring emergency Liver ...
Background/Aims: According to recent prevalence of hepatitis A virus (HAV) infection, acute liver failure ALF) due to HAV infection is observed frequently in parallel. The aim of this study was to elucidate the clinical, laboratory, and pathologic features of patients who have undergone emergency liver transplantation (LT) due to fulminant HAV infection. Methods: Clinical, laboratory, and pathologic data of 11 transplant recipients with anti-HAV IgM-positive ALF between December 2007 and May 2009 were analyzed, and compared with data of 10 recipients who underwent LT for the management of ALF due to other causes. Results: The median age of the patients with HAV-related ALF was 34 years (range: 15-43 years). The levels of hemoglobin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine were higher and the level of bilirubin was lower in the HAV-related ALF group than in the other group (P=0.005, 0.001, 0.001, 0.010, and 0.003, respectively). The time from the onset of initial symptoms to the development of encephalopathy was shorter in the HAV-related ALF group than in the other group (median 5 days, range: 4-13 days; P<0.001). In patients with HAV-related ALF, laboratory findings and clinical prognostic parameters including the Acute Liver Failure Study Group prognostic index, King`s College criteria, and model for endstage liver disease (MELD) and Child-Pugh scores were not associated with the grade of hepatic encephalopathy or time of progression to encephalopathy. Conclusions: The results of this study indicate that the clinical condition of patients with HAV-related ALF requiring emergency LT aggravates rapidly. Prognostic parameters are not sufficient for discriminating transplant candidates in patients with fulminant hepatitis A. (Korean J Hepatol 2010;16:19-28)

Validity and reliability of the nonalcoholic fatty Liver diseases activity score (NAS) in ...
Background/Aim: Nonalcoholic steatohepatitis (NASH) is commonly diagnosed using the semi-quantitative grading and staging system proposed by Brunt et al. in 1999. The Pathology Committee of the NASH established the nonalcoholic fatty liver diseases (NAFLD) activity score (NAS) in 2005. The aim of this study was to elucidate the validity and reliability of the NAS in Korean NAFLD patients. Methods: Fifty-six patients on whom sonography-guided liver biopsy for well-defined NAFLD was performed between 1999 and 2007 were identified retrospectively. Two pathologists evaluated each biopsy sample. NAFLD was evaluated using both the grading system developed by Brunt et al. and the NAS. Each pathologist was blinded to the patients` clinical data and scored independently. We evaluated the body mass index (BMI), liver enzymes, lipid profile, peripheral insulin resistance, leptin, insulin/c-peptide ratio, ferritin, and fasting blood glucose. Results: The patients were aged 32.1±12.5 years (mean±SD) and comprised 44 males (78.6%). Patients with different grades at the two grading systems had mild steatosis or ballooning changes with fibrosis, and 36.6% of them were borderline cases (NAS of 3 or 4). The interobserver agreement on diagnostic category was 0.748 (P<0.001) for the NAS (using weighted κ statistics). Elevated fasting glucose, ALT, and triglyceride were associated with the NAS. Conclusions: The simple and reproducible NAS was found to be a useful pathologic grading system in Korean NAFLD patients. However, the proportion of borderline cases based on the NAS was high. The "wait and see" strategy is necessary for evaluating the long-term prognosis. (Korean J Hepatol 2010;16:29-37)

Clinical efficacy and safety of the combination therapy of peginterferon alpha and ribavirin in ...
Background/Aims: The combination therapy of peginterferon (PEG-IFN) and ribavirin is the standard treatment for hepatitis C virus (HCV) infection. However, few trials have involved patients with cirrhosis. The purpose of this study was to elucidate the efficacy and safety of treatment with PEG-IFN and ribavirin in patients with cirrhosis associated with HCV infection. Method: A total of 65 patients were treated with PEG-IFN alpha-2a/ribavirin (n=32) or PEG-IFN alpha-2b/ribavirin (n=33). PEG-IFN alpha-2a and PEG-IFN alpha-2b were administered at doses of 180 μg/week and 1.5 μg/kg/week, respectively, and ribavirin was administered orally at doses of 800-1200 mg. Patients with HCV genotype 1 and genotype non-1 were treated for 48 and 24 weeks, respectively. The treatment response was assessed based on the sustained virologic response (SVR). Results: The early virologic response (EVR), end-of-treatment response (ETR), and SVR were 70.0%, 52.0%, and 24.0%, respectively, in genotype 1 (n=50). In genotype non-1 (n=15), the ETR was 53.3% and the SVR was 33.3%. The overall SVR did not differ with genotype (1vs non-1, 24.0%vs.33.3%; P=0.471) or between decompensated cirrhosis and compensated cirrhosis (20.0%vs.27.3%, P=0.630). Ten patients developed cirrhotic complications during the treatment, and 11 stopped treatment due to treatment -related adverse events. Conclusion: The combination therapy of PEG-IFN and ribavirin exhibited a low efficacy in cirrhotic patients with HCV infection and was associated with frequent serious complications. However, with careful management of complications, the therapy may have a considerable efficacy in some patients with cirrhosis and HCV infection. (Korean J Hepatol 2010;16:38-48

The relationship between hepatitis B virus infection and the incidence of pancreatic cancer: a ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: An association between past history of hepatitis B virus (HBV) infection and pancreatic cancer (PC) has recently been reported. We investigated whether HBV and hepatitis C virus (HCV) infections are associated with the development of PC in Korea. Methods: We retrospectively recruited patients with PC and sex-and, age-matched control patients with stomach cancer (SC) during the previous 5 years. Serum HBsAg and anti-HCV were examined, and data on smoking, alcohol intake, diabetes, and the history of chronic pancreatitis (CP) were collected. Results: A total of 506 PC and 1008 SC were enrolled, with respectively 58.1% and 97.3% of these cases being confirmed histologically. The mean age and sex ratio male:female) were 63.5 years and 1.5:1 in the PC patients and 63.9 years and 1.5:1 in the SC patients respectively (P>0.05). The odds ratios (95% confidence interval, 95% CI) in univariate analysis were 0.90 0.52-1.56; P=0.70) for HBsAg, 1.87 (0.87-4.01; P=0.11) for anti-HCV, 2.66 (2.04-3.48; P<0.001) for the presence of diabetes, 2.30 (1.83-2.90; P<0.001) for smoking, 1.14 (0.89-1.46; P=0.31) for alcohol intake, and 4.40 1.66-11.66; P=0.003) for the history of CP. Independent risk factors for PC were presence of diabetes (OR, 2.67; 95% CI, 2.00-3.56; P<0.001), smoking (OR, 2.49; 95% CI, 1.93-3.21; P<0.001) and history of CP (OR, 4.60; 95% CI, 1.56-13.53; P=0.006). Conclusions: There was no significant association between seropositivity for HBsAg or anti-HCV and PC. Further studies are warranted to clarify the association between HBV infection and PC in regions where HBV is endemic. (Korean J Hepatol 2010;16:49-56)

Efficacy and predictors of the virologic response to entecavir therapy in nucleoside naive ...
Background/Aims: The aim of this study was to elucidate the antiviral efficacy and the predictors of entecavir treatment in nucleoside-naive chronic hepatitis B patients. Methods: A total of 160 patients treated with entecavir (0.5 mg daily) for at least 24 weeks were consecutively enrolled. The virologic response (HBV DNA<2,000 copies/mL), biochemical response (ALT≤ upper limit of normal), and virologic breakthrough (>1 log10 copies/mL increase in HBV DNA level above nadir on two consecutive occasions) were retrospectively analyzed. Results: The mean follow-up duration was 58.8 weeks, and 85 patients (53.1%) showed HBeAg positivity. The median pretreatment levels of serum ALT and HBV DNA were 99 IU/L and 7.6 log10 copies/mL, respectively. The cumulative rates at 12, 24, 48, and 72 weeks were 37.5%, 68.1%, 87.4%, and 95.8%, respectively, for the virologic response; 40.0%, 66.2%, 84.5%, and 92.7% for the biochemical response; 10.6%, 18.8%, 27.0%, and 34.5% for HBeAg loss; and 3.5%, 7.1%, 9.0%, and 13.2% for HBeAg seroconversion. There was no case of virologic breakthrough. An absence of HBeAg and a low serum HBV DNA level (<8 log10 copies/mL) at baseline were significant predictors of the virologic response in a multivariate analysis (P<0.01). Conclusions: Entecavir therapy showed excellent efficacy in nucleoside-na?ve chronic hepatitis B patients. The predictors of a virologic response were an absence of HBeAg and a low baseline HBV DNA level. (Korean J Hepatol 2010;16:57-65)

Diagnostic usefulness of the random urine Na/K ratio in cirrhotic patients with ascites: a ...
Background/Aims: Twenty-four hour urinary sodium excretion (24-h UNa) of greater than 78 mmol/day is important in the management of cirrhotic ascites. Although the random urine sodium-to-potassium ratio (UNa/K) is strongly correlated with 24-h UNa, and approximately 95% of patients with a random UNa/K greater than 1 have 24-h UNa greater than 78mmol, few data have been published on the correlation between 24-h UNa and random UNa/K. We evaluated diagnostic value of morning and afternoon random UNa/K (AM UNa/K and PM UNa/K, respectively) with 24-h UNa. Methods: A total of 42 male patients were enrolled from October 2007 to March 2008. Each patient collected 5 mL of urine twice at random times during 24-h urine collection (at 10-12 a.m. and 3-5 p.m.). ROC curve analysis was performed to evaluate the feasibility of AM and PM UNa/K for differentiating 24-h UNa greater than 78mmol/day. Results: Forty patients with a 24-h urinary creatinine of greater than 15 mg/kg were analyzed. The 24-h UNa, AM UNa/K, and PM UNa/K were 107.9±91.2mmol (mean±SD), 3.44±3.64, and 3.97±4.60, respectively. When compared with 24-h UNa greater than 78 mmol, AUROC values for AM and PM UNa/K were 0.861 (95% CI, 0.715-0.950) and 0.929 (95% CI, 0.802-0.986), respectively (P=0.0001). No difference was found between the AUROC for AM and PM UNa/K (95% CI, -0.161-0.153, P=0.113). UNa/K greater than 1.25 was sensitive and specific for prediction of 24-h UNa greater than 78 mmol. Conclusions: The results suggest that anytime random UNa/K greater than 1.25 is an accurate, cost-effective, and convenient method for replacing 24-h UNa. Large multicentered cohort studies are needed to confirm our results. (Korean J Hepatol 2010; 16:66-74)

A case report of alverine-citrate-induced acute hepatitis
Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity. (Korean J Hepatol 2010;16:75-78)

A case of hemophagocytic syndrome complicated by acute viral hepatitis A infection

Sat, 01 Jan 2000 00:00:01 +0100
Hemophagocytic syndrome (HPS) is a rare but serious condition that is histopathologically characterized by activation of macrophage or histiocytes with hemophagocytosis in bone marrow and reticuloendothelial systems. Clinically it presents with high fever, hepatosplenomegaly, pancytopenia, liver dysfunction, and hyperferritinemia. Hepatitis A virus is a very rare cause of secondary HPS. We report a case of a 22-year-old woman infected by hepatitis A virus who was consequently complicated with HPS. She presented typical clinical features of acute hepatitis A, and showed clinical and biochemical improvements. However, HPS developed as a complication of acute hepatitis A and the patient died of intraperitoneal bleeding caused by hepatic decompensation and disseminated intravascular coagulation. (Korean J Hepatol 2010;16:79-82)

Cholestyramine resin for erythropoietic protoporphyria with severe hepatic disease: a case report
Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by mutations in the gene encoding the enzyme ferrochelatase. In EPP, deficient ferrochelatase activity leads to the excessive production and biliary excretion of protoporphyrin (PP). The major clinical features of EPP are photosensitivity and hepatobiliary disease that may progress to severe liver disease, that are caused by the toxicity of PP. EPP-related liver disease has been treated medically or surgically including liver transplantation. We described a 20-year-old male with severe liver disease who was diagnosed with EPP based on clinical and laboratory findings. He was treated with cholestyramine resin. Six months after the treatment, he was doing well without any abdominal pain or photosensitivity. (Korean J Hepatol 2010;16:83-88)

Sarcomatoid hepatocellular carcinoma

Jae Yeon Seok , Young Bae Kim

Hepatic eosinophilic abscess presenting as a single nodular mass

Yong Moon Shin, M.D. — Sat, 01 Jan 2000 00:00:01 +0100

The Korean Journal of Predictors of response to therapy with terlipressin and albumin in ...

Oh Sang Kwon, M.D. — Sat, 01 Jan 2000 00:00:01 +0100

Preface

Kyu Sung Rim — Thu, 01 Jan 1970 09:00:00 +0100

Current status of Liver diseases in Korea: Hepatitis A

So Young Kwon — Thu, 01 Jan 1970 09:00:00 +0100

Current status of Liver diseases in Korea: Hepatitis B

Hee Bok Chae , Jong Hyun Kim , Ja Kyung Kim , Hyung Joon Yim — Thu, 01 Jan 1970 09:00:00 +0100

Current status of Liver diseases in Korea: Hepatitis C

Young Suk Lim — Thu, 01 Jan 1970 09:00:00 +0100

Current status of Liver diseases in Korea: Toxic and alcoholic Liver diseases

Kyung Ah Kim — Thu, 01 Jan 1970 09:00:00 +0100

Current status of Liver diseases in Korea: nonalcoholic fatty Liver disease

Sang Hoon Park — Thu, 01 Jan 1970 09:00:00 +0100

Current status of Liver diseases in Korea: Liver cirrhosis

Jeong Won Jang — Thu, 01 Jan 1970 09:00:00 +0100

Current status of Liver diseases in Korea: Hepatocellular carcinoma

Il Han Song , Kyung Sik Kim — Thu, 01 Jan 1970 09:00:00 +0100

Current status of hepatic surgery in Korea

Kyung Sik Kim — Thu, 01 Jan 1970 09:00:00 +0100

Transient elastography, true or false?

Yeon Seok Seo
.

Epidemiology and clinical features of acute hepatitis A: from the domestic perspective

Young Kul Jung , Ju Hyun Kim — Sat, 01 Jan 2000 00:00:01 +0100
Acute viral hepatitis A has recently become a major public health problem in Korea, and the incidence of symptomatic hepatitis A is growing rapidly. With improvements in socioeconomic conditions and environmental hygiene, the chances of exposure to hepatitis A virus (HAV) during childhood have decreased and, in turn, the proportion of young adults with positive anti-HAV has significantly decreased. This has led to the incidence of symptomatic acute hepatitis A increasing since the late 1990s. The incidence of serious complications including fulminant hepatic failure and acute kidney injury has also showed an increasing trend. Variation of the genotype of virus isolated from recent hepatitis A patients suggests an inflow of the hepatitis virus from other countries. In this review article, we present the situation and epidemiology of hepatitis A in Korea, and recommend further investigation and policies for vaccination on a national level. (Korean J Hepatol 2009;15:438-445)

Clinical efficacy of entecavir therapy and factors associated with treatment response in naive ...
Background/Aims: Entecavir is a potent and selective guanosine analogue that has demonstrated a significant antiviral efficacy against hepatitis B virus (HBV). The aim of this study was to characterize the response to entecavir and to examine the factors affecting that response. Methods: We administered 0.5 mg of entecavir once daily for more than 12 months to 114 naive chronic hepatitis B (CHB) patients. We measured the levels of liver enzymes, serological markers, and serum HBV DNA at 3-month interval. Results: Normalization of serum alanine aminotransferase levels was observed in 68.5% (76/114), 74.6% (85/114), and 81.6% (62/76) of patients after 6, 12, and 24 months of therapy, respectively. HBV DNA levels of <50 copies/mL (as evaluated by polymerase chain reaction) were observed in 43.9% (50/114), 71.1% (81/114), and 85.5% (65/76) of patients after 6, 12, and 24 months, respectively. Viral breakthrough was not observed. The rates of HBeAg loss and seroconversion were 43.5% (27/62) and 14.5% (9/62), respectively, after 12 months of therapy, and 56.4% (22/39) and 15.4% (6/39) after 24 months. The independent factor associated with PCR negativity was early virologic response (EVR; HBV DNA <2,000 copies/mL after 3 months of therapy, P<0.001). The independent factors predicting HBeAg loss were found to be serum albumin levels (P=0.041) and EVR (P=0.005). Conclusions: Entecavir induced excellent biochemical and virologic responses in naive CHB patients. EVR was an independent factor for predicting HBV PCR negativity and HBeAg loss. (Korean J Hepatol 2009;15:446-453)

Comparison of various noninvasive serum markers of Liver fibrosis in chronic viral Liver disease
Background/Aims: The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. Methods: We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. Results: There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (≥F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (≥F3). Conclusions: Conclusions: All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis. (Korean J Hepatol 2009;15:454-463)

Factors associated with Liver stiffness in chronic Liver disease
Background/Aims: Transient elastography is a new noninvasive tool for measuring liver stiffness that accurately predicts significant fibrosis and cirrhosis. However, several studies have indicated that liver stiffness can be significantly influenced by major changes in aminotransferase in patients with chronic viral hepatitis. The aim of this study was to determine the factors influencing liver stiffness in patients with chronic liver disease. Methods: We studied 158 patients with chronic liver disease who underwent transient elastography and liver biopsy sampling. Histologic findings on fibrosis and necroinflammatory activity in the biopsy specimens were evaluated according to the Korean Society of Pathologists Scoring System. Routine biochemical tests were performed according to standard methods. Results: Liver stiffness was strongly correlated with liver fibrosis stage (Spearman coefficient=0.636, P<0.001), lobular activity (Spearman coefficient=0.359, P<0.001), and portoperiportal activity grade (Spearman coefficient=0.448, P<0.001). Liver stiffness was significantly associated with serum levels of total bilirubin (P=0.025), direct bilirubin (P=0.049), gamma-glutamyl transpeptidase (P=0.014), platelet count (P=0.004), albumin (P<0.001), and international normalized ratio (P<0.001). Multivariate analysis showed that fibrosis stage (B 3.50, P=0.009) and lobular activity grade (B 3.25, P=0.047) were independently associated with liver stiffness. Conclusions: Liver stiffness as measured by transient elastography is associated with the grade of necroinflammatory activity and the stage of fibrosis, irrespective of serum ALT levels. (Korean J Hepatol 2009;15:464-473)

Comparison of radiofrequency ablation and transarterial chemoembolization for the treatment of ...
Background/Aims: Radiofrequency ablation (RFA) is an established curative therapeutic modality for unresectable hepatocellular carcinoma (HCC), and transarterial chemoembolization (TACE) has been used as a palliative treatment for inoperable HCC. It is still unknown whether RFA and TACE are equally effective for improving the survival of patients with unresectable HCC that is amenable to either treatment. The aim of this retrospective study was to compare the clinical impacts of two treatments, and analyze the prognostic factors for recurrence and survival. Methods: Ninety-three patients with a single HCC smaller than 4 cm who showed complete responses (complete ablation or complete lipiodol tagging) after treatment with RFA (n=43) or TACE (n=50) between January 2002 and February 2009 were investigated. Univariate and multivariate analyses were performed for 13 potential prognostic factors using the Cox proportional-hazards model. Results: The time-to-recurrence rates at 1, 2, and 3 years after treatment were 32.9%, 44.3%, and 55.4%, respectively, for the RFA group, and 42%, 68.3%, 71.7% for the TACE group. The probability of survival at 1, 2, and 3 years was 97.7%, 77.4%, and 63.1%, respectively, for the RFA group, and 95.9%, 76.1%, and 60.2% for the TACE group. The time-to-recurrence and overall survival rates did not differ significantly between the two treatment groups. A multivariate Cox proportional-hazards model revealed that a tumor size larger than 3 cm and lower serum albumin levels were independent risk factors for recurrence, and that being male, being seropositive for hepatitis B surface antigen, and having a higher serum albumin level were independent favorable prognostic factors for survival. Conclusions: TACE and RFA exhibited similar therapeutic effects in terms of recurrence and survival for patients with a single HCC smaller than 4 cm, if they could exhibited complete responses. (Korean J Hepatol 2009;15:474-485)

Transcriptional profiling and Wnt signaling activation in proliferation of human hepatic ...
Background/Aims: This study aimed to better understand gene expression profiles of human hepatic stellate cell (HSC) activation and the relationship with the Wnt signaling pathway. Methods: The global transcript levels in platelet derived growth factor-BB (PDGF-BB)-stimulated hTERT HSCs were analyzed using oligonucleotide microarrays. Oligonucleotide microarrays with 19K human oligo chips were performed to obtain gene expression profiles associated with proliferation in human hTERT HSCs. The microarray data was verified by real time quantitative PCR and expression of the components of Wnt signaling was analyzed by Western blot. Results: Microarray data showed 243 up-regulated and 265 down-regulated genes in PDGF-BB-treated HSCs. The changes in expression of glypican3 and BH3 interacting domain death agonist (BID) mRNA in real time quantitative PCR, especially among the highly up- or down-regulated genes, were statistically consistent with the microarray data. The Wnt signaling pathway components, frizzled10 (FZD10) and calcium/calmodulin-dependent protein kinase II alpha (CAMK2A), showed increased expression in the short time course microarray and the up-regulation of FZD10 also occurred at the protein level. Our data showed various gene expression profiles during activation of human HSC. Conclusions: The up-regulated expression of FZD10 and CAMK2A suggests that the Wnt/Ca²⁺ signaling pathway is active in hTERT HSCs and may participate in HSC activation and proliferation. (Korean J Hepatol 2009;15:486-495)

A comparison of 24- vs. 48-week peginterferon plus ribavirin in patients with genotype 1 ...
Background/Aims: The standard therapy for patients with genotype 1 chronic hepatitis C (CHC) is a combination of peginterferon and ribavirin for 48 weeks. However, the most appropriate duration of treatment remains to be established because of treatment-related side effects and cost. The aim of this study was to compare the efficacies of 24- and 48-week treatments, and to assess the efficacy of split 24-week therapy (a further 24 weeks of treatment in patients with relapse after the initial 24 weeks of treatment). Methods: A total of 130 patients with genotype 1 CHC was treated between June 2004 and December 2006. Patients with undetectable HCV RNA at 24 weeks of treatment (as assessed by qualitative PCR assay; n=101 patients) were allowed to choose either 24 or 48 weeks as the duration of their treatment; 51 patients chose the 24-week treatment regimen and the remainder chose the 48-week regimen. Patients who relapsed after 24 weeks of treatment were treated for further 24 weeks. The sustained virologic response (SVR) of each treatment group was analyzed. Results: The SVR rate was higher in patients treated for 48 weeks than in those treated for 24 weeks (74.0% vs. 52.9%, P=0.028). In the multivariate analysis, age < 50 years, platelets ≥ 150,000/mm3, and treatment duration for 48 weeks remained significant independent predictors of SVR. Fourteen of the 24 patients who relapsed in the 24-week treatment group received split 24-week therapy, and 6 patients (42.9%) achieved SVR. The overall SVR rate did not differ significantly between the 24-week treatment group, including those who underwent 24-week split therapy (64.7%), and the 48-week treatment group (64.7% vs. 74%, P=0.311). Conclusions: The 24-week plus additional split 24-week therapy following failure is a useful treatment strategy for patients with genotype 1 CHC. (Korean J Hepatol 2009;15:496-503)

Two cases of toxic hepatitis caused by arrowroot juice

Sat, 01 Jan 2000 00:00:01 +0100
Herbal remedies and health foods are widely used, and their side effects have been reported. We describe two cases of symptomatic toxic hepatitis that developed in middle-aged women after ingesting arrowroot juice. The clinical manifestations were nausea, vomiting, and jaundice. The diagnosis of toxic hepatitis was made using the Roussel Uclaf Causality Assessment Method score on the basis of the patient`s history and laboratory data. After supportive care, the patients showed rapid improvements of clinical symptoms, laboratory findings, and liver stiffness. Clinicians should be aware that the consumption of arrowroot juice can cause toxic hepatitis. (Korean J Hepatol 2009;15:504-509)

A case of primary hepatic epithelioid hemangioendothelioma with spontaneous rupture

Sat, 01 Jan 2000 00:00:01 +0100
Primary hepatic epithelioid hemangioendothelioma is a rare neoplasm of endothelial origin. The clinical manifestations are nonspecific, ranging from complete absence of symptoms to hepatic failure and death. Spontaneous rupture of a hepatic epithelioid hemangioendothelioma is an extremely rare presentation. We present a case of primary hepatic epithelioid hemangioendothelioma in a 65-year-old male patient with alcoholic liver cirrhosis. He was hospitalized due to epigastric pain and multiple liver masses on abdominal ultrasound. Dynamic liver CT imaging revealed multiple peripheral nodular enhanced mass lesions with delayed centripetal enhancement, and the adjacent collection of high-attenuation fluid along the liver capsule. Abdominal tapping revealed blood in the peritoneal cavity. Primary hepatic epithelioid hemangioendothelioma with spontaneous rupture was finally diagnosed based on a histopathologic examination revealing positive immunohistochemical staining for CD34. (Korean J Hepatol 2009;15:510-516)

A case of acute cholestatic hepatitis induced by Corydalis speciosa Max.
Herbs are widely used as treatments for various symptoms. However, several herbs have been reported to be inducers of liver injury. We report herein a case of hepatotoxicity induced by Corydalis speciosa Max. A 37-year-old male complained of jaundice and mild abdominal discomfort. A thorough history was taken, and laboratory investigation, diagnostic imaging studies, and percutaneous liver biopsy sampling were conducted to determine the cause of liver injury. An accurate cause was not revealed. We administered supportive management for acute cholestatic hepatitis of unknown origin, after which his symptoms disappeared and serum aminotransferase levels decreased gradually to near normal levels. However, at 2 months after discharge, the symptoms and the elevation of aminotransferase levels recurred. At that time he told us that he had repeatedly but unintentionally eaten a herb called “Hwang-geun cho”(Corydalis speciosa Max.). Thus, we diagnosed his case as herbal hepatotoxicity. (Korean J Hepatol 2009;15:517-523)

Intrahepatic cholangiocarcinoma associated with Clonorchis sinensis infection

Yoon Mi Jeen , So Young Jin
.

Neuroendocrine tumors of the Liver

Won Jae Lee
.

The Korean Journal of Role of cadherin-17 in hepatocellular carcinoma

Tae Ho Hahn
.

2009 AASLD Highlights : Topic related to hepatitis B, virology and pathogenesis

Hyung Joon Yim
.

2009 AASLD Highlights : Topics related to the therapy of hepatitis B

Byung Seok Kim
.

2009 AASLD Highlights : Topics related to hepatitis C, virology and pathogenesis

Woo Jin Chung
.

2009 AASLD Highlights : Topics related to the therapy of hepatitis C

Hyun Woong Lee
.

2009 AASLD Highlights : Topics related to Liver fibrosis

Seung Up Kim
.

2009 AASLD Highlights : Topics related to Liver cirrhosis and its complications: Ascites, ...

Jong Kyu Park
.

2009 AASLD Highlights : Topics related to the complications of Liver cirrhosis: Portal ...

Yeon Seok Seo
.

2009 AASLD Highlights : Topics related to hepatocellular carcinoma

Byung Seok Lee
.

2009 AASLD Highlights : Topics related to the treatment of hepatocellular carcinoma

Soo Young Park
.

2009 AASLD Highlights : Topics related to non-alcoholic fatty Liver disease

Ki Tae Yoon
.

2009 AASLD Highlights : Topics related to alcoholic Liver disease

Moon Young Kim
.

Haplotype analysis at R778L mutation of ATP7B gene in Korean patients with Wilson disease

Hyun Seok Jin , Berm Seok Oh
.

Molecular targeting for treatment of advanced hepatocellular carcinoma

Il Han Song
Hepatocellular carcinoma (HCC) is a major global health problem, which has a grave morbidity and mortality. Over the past few decades, no effective systemic therapeutic modalities have been established for patients with the unresectable HCC in advanced stage. Sorafenib is a small molecule that blocks cancer cell proliferation by targeting the intracellular signaling pathway at the level of Raf-1 and B-Raf serine-threonine kinases, and exerts an anti-angiogenic effect by targeting the vascular endothelial growth factor receptor-1, 2 and 3, and platelet-derived growth factor receptor-β tyrosine kinases. Recently, two clinical successful applications, SHARP and Asia-Pacific trial, of multikinase inhibitor sorafenib represent a significant advance in the treatment of advanced HCC patients without a curative chance. However, because the results of clinical trials show diverse responses in a subset of HCC patients, a molecular classification of HCC through the excavation of specific biomarkers related to its biological behavior is necessary for sorting HCC patients to each group with a biological homogeneity, ultimately leading to the most suitable individualization of molecular targeted therapy in HCC. (Korean J Hepatol 2009,15:299-308)

Haplotype analysis and possible founder effect at the R778L mutation of the ATP7B gene in ...

Sun Hwan Bae, M.D.*, Jong Won Kim, M.D.1, Jeong Kee Seo, M.D. — Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Wilson`s disease (WD) is an inherited disorder of copper metabolism caused by alteration of the P-type adenosine triphosphatase (ATP) 7B gene. In this study, we analyzed the frequency of well-known mutations and constructed the first haplotypes for Koreans. In addition, we evaluated whether a founder effect existed in Korean patients with WD. Methods: We obtained DNA samples from 21 patients with WD and their parents (total cohort n=63). ATP7B gene mutations were identified by direct sequencing methods, and microsatellite typing was performed at D13S315, D13S1325, and D13S316 with fluorescent dye-labeled primers. Any founder effect was identified by using 42 normal alleles from parents with a normal phenotype as a control group. The x2 test and Fisher`s exact test were used for statistical analysis. Results: Three common mutations were found in 23 chromosomes obtained from 21 patients: the R778L mutation at exon 8 (15/23, 65.2%), the A874V mutation at exon 11 (6/23, 26.1%), and the N1270S mutation at exon 18 (2/23, 8.7%). D13S315 and D13S316 showed linkage disequilibrium at alleles 5 and 4, respectively, in patients with the R778L mutation (P=0.0157 and 0.0001, respectively). The haplotype made up of these two alleles occurred significantly more frequently in patients with the R778L mutation (5-R778L-4, D13S315-mutation-D13S316) than in the controls (P=0.0018). Conclusions: The arche haplotype of the ATP7B gene in Korean patients with WD may be 5-R778L-4 (D13S315-mutation-D13S316), and it might illustrate a founder effect. (Korean J Hepatol 2009,15:309-319)

Prognostic value of serum osteopontin in hepatocellular carcinoma patients treated with ...
Background/Aims: Osteopontin (OPN) is overexpressed in hepatocellular carcinoma (HCC) with postoperative recurrence or extrahepatic metastasis. However, its prognostic value in patients treated with transarterial chemoembolization (TACE) is unclear. We investigated the utility of serum OPN levels and changes therein as prognostic markers in HCC patients who have received TACE. Methods: Forty-six patients with HCC were enrolled. Serum OPN levels were measured before and 4 weeks after TACE. Serum biochemistry and computed tomography (CT) scans were analyzed. We evaluated baseline serum OPN levels and subsequent changes therein in relation to tumor responses and cumulative survival rates following TACE. A decreasing pattern was defined as a decrease after TACE of more than 10% relative to baseline levels. A "responder" was defined as a patient who exhibited a tumor necrosis rate of higher than 50% on the follow-up CT scan. Results: Higher initial serum OPN levels were associated with a large tumor, portal vein invasion, and an advanced tumor stage. Patients who had lower initial serum OPN levels and those who exhibited decreasing patterns after TACE tended to have more favorable tumor responses (P=0.043 and 0.055, respectively) and exhibited better cumulative survival rates (P=0.036 and 0.030, respectively). However, the initial serum OPN level and subsequent changes in serum OPN levels were not independent predictors for survival on multivariate analysis. Conclusions: Serum OPN levels were significantly higher in patients with advanced HCC. In addition, HCC patients with low pretreatment serum OPN levels and those for whom serum OPN declined following TACE exhibited better tumor responses and survived for longer. (Korean J Hepatol 2009,15:320-330)

Efficacy of 48-week clevudine therapy for chronic hepatitis B
Background/Aims: Clevudine is a nucleoside analogue that exhibits potent and sustained antiviral effects as a 24-week therapy for chronic hepatitis B (CHB). This study evaluated the efficacy and viral resistance of a 48-week course of clevudine treatment for CHB. Methods: Data on patients with CHB and detectable serum hepatitis B virus (HBV) DNA who were treated with clevudine for 48 weeks or longer were collected retrospectively for this study. Patients who had taken lamivudine within the 3 years prior to this study were excluded. Serum HBV DNA was measured by polymerase chain reaction hybridization (lower detection limit=316 copies/mL). Serum HBV DNA and biochemical data were analyzed at weeks 24 and 48. Developments of viral breakthrough and resistance to the antiviral drug were also monitored. Results: Data from 74 patients (mean age 44 years; M:F=54:20; HBeAg-positive, 47; HBeAg-negative, 27) were included in this study. Ten patients had experienced previous lamivudine treatment. Median HBV DNA at baseline was 6.49 log10 copies/mL. Median serum HBV DNA reductions from baseline at week 48 were -4.34 log10 copies/mL (HBeAg-positive, -4.84 log10 copies/mL; HBeAg-negative, -3.74 log10 copies/mL). At week 48, serum HBV DNA was not detected in 83.8% of the patients (HBeAg-positive, 76.6%; HBeAg-negative, 96.3%). Normalization of serum alanine aminotransferase levels was achieved in 84.7% of the patients. Viral breakthrough and antiviral resistance developed in two patients at week 48. The development of antiviral resistance was associated with the presence of previous lamivudine treatment and cirrhosis. Conclusion: A 48-week course of clevudine therapy was highly effective in patients with CHB. The risk of development of resistance to clevudine was increased in patients with previous exposure to lamivudine and cirrhosis. (Korean J Hepatol 2009;15:331-337)

Impact of adherence to peginterferon-ribavirin combination therapy in chronic hepatitis C ...
Background/Aims: Various predictive factors for peginterferon alpha and ribavirin therapy in chronic hepatitis C have been reported, but the effect of adherence to therapy has not been established. We investigated how adherence affects the sustained virologic response (SVR). Methods: We analyzed 92 chronic hepatitis C patients receiving peginterferon alpha and ribavirin combination therapy. Patients were first identified as having either genotype 1 or genotype non-1 infection and then categorized into three groups according to their adherence to the treatment protocol: (1) patients who received ≥80% of the recommended dosage of both peginterferon alpha and ribavirin for ≥80% of the intended duration of therapy, (2) patients who received <60% of the recommended dosage of both peginterferon alpha and ribavirin for <60% of the intended duration of therapy, and (3) patients who were not included in either group 1 or 2. Results: The rates of early virologic response, end of treatment response, and SVR differed significantly with the degree of adherence to the treatment. The SVRs of genotype 1 patients were 86.7%, 26.7%, and 66.7% in groups 1, 2, and 3, respectively (P=0.003), and those of genotype non-1 were 100%, 16.7%, and 88.9%, respectively (P<0.001). Conclusions: Adherence to therapy is a key factor in achieving an SVR. Supportive strategies to improve adherence will increase overall SVR rates. (Korean J Hepatol 2009;15:338-349)

Comparison of the Model for End-stage Liver Disease and hepatic venous pressure gradient for ...
Backgrounds/Aims: This study compared the prognostic values of the Model for End-stage Liver Disease (MELD) and the hepatic venous pressure gradient (HVPG) in the prediction of death within 3 and 12 months in patients with decompensated liver cirrhosis. Methods: We used data from 136 consecutive patients with decompensated cirrhosis who underwent HVPG between January 2006 and June 2008. Cox regression analysis was used to investigate the independent relationships with death of MELD and HVPG. The prognostic accuracies of MELD and HVPG were analyzed by calculating the area under the receiver operating characteristic curve (AUROC) for the occurrence of death within 3 and 12 months. Results: Both MELD and HVPG were independent predictors of death [hazard ratio (HR)=1.11 and 1.12, respectively; 95% confidence interval (CI)=1.04~1.20 and 1.08-1.16]. Analysis of the AUROC demonstrated that the prognostic power did not differ between MELD and HVPG for predicting the 3-month survival (HR=0.76 and 0.68, respectively; 95% CI=0.62~0.89 and 0.52~0.84; P=0.22) or the 12-month survival (HR=0.72 and 0.73, 95% CI=0.61~0.83 and CI=0.61~0.84). Conclusions: Both MELD and HVPG are independent prognostic factors of death within 3 and 12 months in patients with decompensated liver cirrhosis, and their accuracies are similar. However, HVPG has a limited role in the prediction of death in decompensated cirrhosis due to its invasiveness and limited use. (Korean J Hepatol 2009;15:350-356)

A case of metastatic hepatocellular carcinoma of the rib, treated by transcatheter arterial ...
Bone is a common site of metastasis in patients with hepatocellular carcinoma (HCC). We report a rare case of rib metastasis from HCC treated by transcatheter arterial chemoembolization (TACE). A 55-year-old man with liver cirrhosis presented with right lower chest pain. The diagnosis was an HCC with a bone metastasis in the right eighth rib. Intra-arterial injections of doxorubicin mixed with Lipiodol and Gelfoam particles were instituted through the right eighth intercostal artery. Computed tomography and a Tc99-labeled scan performed 2 months after the third TACE revealed no viable HCC in the right eighth rib. (Korean J Hepatol 2009;15:357-361)

Four patients with hepatitis A presenting with fulminant hepatitis and acute renal failure and ...
Hepatitis A is generally known as a mild, self-limiting disease of the liver, but in rare instances it can progress to fulminant hepatitis, which may require liver transplantation for recovery. Such cases are known to be related to old age and underlying liver disease. We report four cases of hepatitis A in which patients presented with fulminant hepatitis and acute renal failure and underwent liver transplantation. The following common features were observed in our cases: (1) occurrence in relatively old age (≥39 years old), (2) association with acute renal failure, (3) presence of hepatomegaly, and (4) microscopic features of sub-massive hepatic necrosis. (Korean J Hepatol 2009;15:362-369)

A case of sudden-onset hearing Loss in a patient treated with peginterferon
Combination therapy of pegylated interferon α and ribavirin has been associated with various adverse effects, but sudden-onset hearing loss is uncommon. We report a 60-year-old male patient who developed sudden-onset hearing loss during combination therapy with pegylated interferon α and ribavirin for chronic hepatitis C. This patient had been diagnosed with chronic hepatitis C (genotype Ib) and early-stage liver cirrhosis 3 years previously, and had been treated with conventional interferon-α and ribavirin for 12 months. However, 6 months from the end of the treatment course the patient relapsed and received combination retreatment with pegylated interferon α-2b and ribavirin. He developed sudden-onset right-side hearing loss and tinnitus 42 weeks after the start of this retreatment. Pure-tone audiometry revealed a right-side hearing loss of 60~90dB. The patient consequently immediately discontinued the pegylated interferon therapy and was given prednisone 60 mg/day for 10 days, after which the hearing loss had almost completely recovered. (Korean J Hepatol 2009;15:370-374)

Large Liver cell change/dysplasia in hepatitis B virus-related Liver cirrhosis

Haeryoung Kim, M.D., Ph.D., Young Nyun Park, M.D., Ph.D.1
.

Peliosis hepatis

Won Jae Lee
.

The Korean Journal Of Clinical outcomes and development of hepatocellular carcinoma after HBsAg ...

Ji Hoon Kim
Background & Aims: Our aims were to study the virologic, histologic, and clinical outcome in chronic hepatitis B (CHB) patients with hepatitis B surface antigen (HBsAg) seroclearance. Methods: We determined the age of HBsAg seroclearance that is associated with a lower risk for hepatocellular carcinoma (HCC) in 298 CHB patients (median follow-up, 108 months). The following virologic and histologic features were also determined: liver stiffness (n=229), liver histology, serum HBV DNA levels over time (n=265), intrahepatic HBV DNA with covalently closed circular DNA (cccDNA) levels, and messenger RNA (mRNA) expression. Results: The median age of HBsAg seroclearance was 49.6 years. Seven (2.4%) patients developed HCC. Cumulative risk for HCC was higher in patients with HBsAg seroclearance at ages >50 years compared with those with HBsAg seroclearance at ages <50 (P≥0.004) years. Of these 2 groups of patients, 29.5% and 7.9%, respectively, had significant fibrosis by liver stiffness measurement (P=0.001), and 15.4% of patients had mild histologic fibrosis. Intrahepatic total HBV DNA and cccDNA were detected in 100% and 79.3% of patients, respectively. All patients had undetectable surface and precore/pregenomic RNA transcripts. One (9.1%) patient had X mRNA expression. Serum HBV DNA were detectable in 13.4%, 6.1%, and 3.7% of patients within 1 year and 5~10 and >10 years after HBsAg seroclearance, respectively, and 82.1% patients had persistently normal alanine aminotransferase levels. Conclusions: HBV persisted at low replicative and transcriptional levels after HBsAg seroclearance. HBsAg seroclearance at age <50 years was associated with a lower risk for the development of HCC.

Special Contribution : Practice guidelines for management of hepatocellular carcinoma 2009

Korean Liver Cancer Study Group and National Cancer Center, Korea — Sat, 01 Jan 2000 00:00:01 +0100
Hepatocellular carcinoma (HCC) is a major cancer in Korea, typically has a poor prognosis, and constitutes the majority of primary hepatic malignancies. It is the number one cause of death among people in their 50s in Korea. The five-year survival rate of liver cancer is poor; at 18.9%. Efforts to increase the survival rate through early diagnosis of HCC and optimal treatments are keenly needed. Western guideline for the management of HCC were developed, but these guidelines are somewhat unsuitable for Korean patients. Thus, the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC), Korea jointly produced the Clinical Practice Guidelines for HCC for the first time in Korea in 2003. Owing to medical advances over the following six years, diagnosis and treatment of HCC has changed considerably. As more national and foreign data are accumulated, KLCSG and NCC, Korea recently revised the Clinical Practice Guidelines for HCC. Forty or more specialists in the field of hepatology, general surgery, radiology and radiation oncology participated, and meticulously reviewed national and foreign papers, and collected opinions through advisory committee conferences. These multidisciplinary, evidence-based guidelines summarized diagnosis, surgical resection, liver transplantation, local treatments, transarterial chemoembolization, radiation therapy, chemotherapy, preemptive antiviral treatments, and response evaluation of HCC. These Korean guidelines are expected to be useful for clinical management of and research on HCC. (Korean J Hepatol 2009;15:391-423)

Clevudine therapy in patients with chronic hepatitis B

Kwan Sik Lee

Pathology of nonalcoholic steatohepatitis

Yoon Mi Jeen , So Young Jin — Sat, 01 Jan 2000 00:00:01 +0100
Nonalcoholic steatohepatitis (NASH), one of the NAFLDs (nonalcoholic fatty liver diseases), is regarded as a hepatic manifestation of metabolic syndrome. NASH can progress to cirrhosis, and possibly to hepatic malignancy. Currently, liver biopsy is the only reliable method of assessing the presence or absence of NASH and the stage of fibrosis. The finding of steatosis with evidence of hepatocyte injury such as inflammation, ballooning, degeneration, and/or fibrosis, is generally essential for making a diagnosis of NASH. However, its diagnostic criteria have not yet been established. The pathologic findings of NASH and related diseases, and the grading system currently in use are reviewed herein. (Korean J Hepatol 2009;15:122-130)

Change in the serologic markers of hepatitis B after allogenic hematopoietic stem-cell ...
Backgrounds/Aims: This study examined the effects of hepatitis B virus (HBV) infection state and immunologic capability in both the recipients and donors of allogenic hematopoietic stem-cell transplantation (allo-HSCT) on changes in HBV serologic markers in recipients. Methods: A total of 537 patients underwent allo-HSCT for the treatment of leukemia, malignant lymphoma, and solid tumor. HBV serologic markers were examined in both recipients and donors prior to and following the transplantation. The mean follow-up period was 36.6 months (range 3-80 months). Results: Of the 537 patients who underwent allo-HSCT, 45 recipients were positive for HBsAg prior to transplantation. Of these 45 patients, 21 were transplanted from anti- HBs-positive donors and the remaining 24 were transplanted from anti-HBs-negative donors. In the former cases, seroconversion was noted in 4 of the 21 patients (19%). In the latter cases, however, no seroconversion was noted following the transplantation. Thirty patients who were negative for both HBsAg and anti-HBs were transplanted from anti-HBs-positive donors, and 15 out of 30 patients (50%) acquired anti-HBs. Four hundred and seven patients who were positive for anti-HBs were transplanted from anti-HBs-positive or HbsAg-negative donors; 8 of these proved HBsAg-positive following the transplantation. There were no changes in HBV serological markers following transplantation in 41 patients who were transplanted from HbsAg-positive donors. Conclusions: Due to the adoptive immunity that was transferred from anti-HBspositive donors, a seroconversion of HBsAg could occur in some HBsAg-positive recipients. HBsAg-positive donors had a lesser effect on the HBV serologic markers of recipients. However, a reactivation of HBV can occur following hematopoietic stem-cell transplantation in the cases of recipients or donors with a history of HBV, infection by an accompanying immune suppression. Therefore, prevention should be instigated. (Korean J Hepatol 2009;15:131-139)

Distribution of hepatitis B virus genotypes in Korea
Backgrounds/Aims: Considering the incidence of prevailing hepatitis B virus (HBV) genotypes in neighboring nations, the predominance of genotype C in Korea is exceptional and needs to be confirmed by nationwide investigation. Methods: A total of 510 HBsAg (+) or HBeAg (+) serum samples was collected from subjects in several cities and harbors throughout the Korean peninsula for genotype (A-G)-specific multiplex PCR analysis. Another 40 serum samples from chronic HBV carriers from Iksan city were selected for sequencing of the entire HBV genome. Phylogenetic analysis was performed with 22 whole genomic sequences of Korean HBV strains enrolled in GenBank. Results: An amplicon was found in 377 specimens and genotype C occupied 98.1% (370 cases); none of the other genotypes were found. A mixed pattern of genotypes B and C was seen in seven specimens (1.9%), of which five were tested using PCR targeting the X fragment; no genotype B bands were found. With the exception of 1 case, which was subgenotype A2, whole sequences of Korean HBV strains (n=62) belonged to subgenotype C2. Conclusions: The prevailing HBV genotype in Korea is C2; the other genotypes occur only rarely. Future studies should include confirmation of the detection of genotypes other than C. (Korean J Hepatol 2009;15:140-147)

Analysis of the clinical characteristics and prognostic factors of ruptured hepatocellular carcinoma
Background/Aims: Spontaneous rupture of hepatocellular carcinoma (HCC) is a rare but life-threatening complication. Although the prevalence rate and mortality of HCC has been reportedly high in Korea, studies on ruptured HCC are limited. The aim of this study was to determine the clinical characteristics and prognostic factors of ruptured HCC. Methods: Among 886 cases with HCC that had been diagnosed at Chonnam National University Hospital from January 2002 to December 2007, 62 cases (7.0%) with ruptured HCC were studied retrospectively regarding their clinical characteristics and prognostic factors. Results: Transarterial embolization was performed in 56 cases (90.3%) to control bleeding, with a hemostasis success rate of 89.3%. The survival time after the rupture of HCC was 8.0±1.7 months (mean±SD), although it was longer in HCC cases that were first diagnosed in a ruptured state or ruptured with a small amount of bleeding than in those that ruptured during follow-up after diagnosis or with a large amount of bleeding, respectively. The 30-day mortality rate in patients with a ruptured HCC was 43.5%, and the early deaths were independently associated with the presence of hepatic encephalopathy (odds ratio, OR=44.7; 95% confidence interval, CI=1.9-1051.1; P=0.018), serum bilirubin >3.0 mg/dL (OR=36.7; 95% CI=1.3-1068.5; P=0.036), and the massive or diffuse type of tumor morphology (OR=53.5; 95% CI=3.0-964.2; P=0.007). Conclusions: The prognosis in patients with ruptured HCCs was poor with a 30-day mortality of 43.5%. The early deaths after the rupture of HCC were associated with elevated serum bilirubin levels, hepatic encephalopathy, and the massive or diffuse type of tumor morphology. (Korean J Hepatol 2009;15:148-158)

Clinical features of hepatic tuberculosis in biopsy-proven cases
Backgrounds/Aims: Hepatic involvement is frequently observed in patients with miliary tuberculosis, but primary hepatic tuberculosis with no clinical extrahepatic manifestations of tuberculosis is uncommon. With the ever-increasing number of immunocompromised patients, it is expected that hepatic tuberculosis will occur more frequently. The aim of the present study was to establish the clinical manifestations and course of the disease. Methods: From January 1989 to September 2008, 12 patients were diagnosed with hepatic tuberculosis by liver biopsy at Seoul National University Hospital. We retrospectively evaluated their clinical, laboratory, and imaging findings by medical record review. Results: Four patients had primary hepatic tuberculosis, and eight patients had hepatic tuberculosis secondary to pulmonary or miliary tuberculosis. Three patients were immunocompromised, and six patients had no previous medical problem. An elevated serum level of alkaline phosphatase was the most frequently observed finding in laboratory tests. Imaging studies showed variable findings, including hepatosplenomegaly, multiple hepatic nodules, abscess formation, and even normal findings. Ten patients responded to antituberculosis drugs, and two cases with tuberculous liver abscess had persistent disease despite prolonged therapy. Conclusions: In patients with a protracted illness, hepatosplenomegaly and/or abnormal liver function tests, hepatic tuberculosis should be suspected, even in healthy young patients or patients with normal imaging findings. Patients with tuberculous abscess formation tend to respond poorly to antituberculosis therapy, and surgery could be considered in these patients. (Korean J Hepatol 2009;15: 159-167)

Comparison of Lamivudine-induced HBsAg Loss rate according to age in children with chronic ...

Jung Mi Kim , Byung Ho Choe , Mi Ae Chu , Seung Man Cho
Background/Aims: The aim of this study was to establish the characteristics of children with hepatitis B e antigens (HBeAg) positive chronic hepatitis B who were cleared of hepatitis B surface antigens (HBsAg) as a result of lamivudine treatment. Methods: Seventy-six children with chronic hepatitis B who were seropositive for HBeAg were treated with lamivudine for at least 6 months. HBeAg seroconversion occurred during treatment in 49 of these children, who were then followed up to assess their clearance of serum HBsAg. Various clinical variables were compared between those patients who were cleared of HBsAg and those who were not, including age, pretreatment serum levels of alanine aminotransferase (ALT) and hepatitis B virus (HBV) DNA, treatment duration, the time elapsed between initiation of treatment and ALT normalization, HBV DNA negativization, HBeAg seroconversion, and HBsAg clearance. Results: HBsAg disappeared in 13 of the 49 (26.5%) patients who experienced lamivudine-induced HBeAg seroconversion; HBsAg did not reappear during follow-up period (1-86 months). The time that elapsed between initiation of lamivudine treatment and total HBsAg clearance was 25.9±27.1 months (mean±SD; range: 5-104 months). The age at which treatment was initiated was the only factor associated with HBsAg clearance. Children who were cleared of HBsAg were significantly younger than those who were not (5.1±4.3 years vs. 7.9±4.9 years, respectively; P=0.006). All 13 of these patients eventually produced antibodies to HBsAg. Conclusions: Younger children (age <7 years old) have a higher chance of HBsAg clearance than older children after the treatment of HBeAg-positive chronic hepatitis B with lamivudine. (Korean J Hepatol 2009;15:168-178)

Long-term clevudine therapy in nucleos(t)ide-naive and Lamivudine-experienced patients with ...
Backgrounds/Aims: Clevudine is an effective antiviral nucleoside analogue, but there are few data regarding its long-term effects, resistance, and safety. The aim of this study was to evaluate the long-term clinical efficacy of clevudine over a 1-year treatment period in nucleos(t)ide-naive and lamivudine-experienced chronic hepatitis B patients. Methods: Nucleos(t)ide-naive (group A, n=196) and lamivudine-experienced (serum hepatitis B virus, HBV DNA >2,000 copies/mL without resistant mutants at the start of clevudine therapy, group B, n=75) patients were included in this study. Basic clinical characteristics including age, sex, the presence of cirrhosis, laboratory data, and hepatitis B surface antigen (HBeAg) positivity were similar between the two groups. Pretreatment serum levels of HBV DNA were 7.4 and 6.6 log10 copies/mL (P<0.001). The mean treatment duration was 8 months for both groups (range for group A: 3-21 months; range for group B: 3-20 months). Genotypic analysis for resistant mutations in the reverse transcriptase of HBV was performed after viral breakthrough. Results: After 1 year of therapy, 75.0% and 51.9% of groups A and B, respectively, had HBV DNA levels of <2,000 copies/mL (P=0.032), and HBeAg seroconversion rates were 16.9% and 16.7%, respectively. The rates of viral breakthrough at 1 year were 10.0% (8/80) and 44.4% (12/27), respectively (P<0.001). Proven sites of mutation of HBV DNA polymerase in naive patients were, for example, L80I, L180M, A181V/T, M204I and V207I. Ten patients complained of prominent fatigue and revealed elevated serum levels of aspartate aminotransferase (AST) and creatine phosphokinase (CPK). Two of these patients presented with severe myopathy from which they recovered completely after quitting clevudine. Conclusions: Clevudine is one of the recommended first-line medicines for the treatment of chronic hepatitis B, but it is not free from resistance, particularly in patients with a history of previous lamivudine treatment, but also in naive patients. Clevudine should be avoided in previously lamivudine-exposed patients. In addition, reelevation of serum AST and CPK levels is not a rare occurrence, and close observation and follow-up tests are essential. (Korean J Hepatol 2009;15:179-192)

A case of hypervascular hyperplastic nodules mimicking hepatocellular carcinoma in alcoholic ...
Benign hypervascular hyperplastic nodules (HHN) in liver cirrhosis are very rare. It is important to distinguish between regenerative nodules (hyperplastic nodules) and tumorous nodules (dysplastic or neoplastic nodules) in hepatocellular nodular lesions. The differential diagnosis between HHN and hepatocellular carcinoma on the basis of radiologic imaging is often difficult, and is clinically important when determining the therapeutic plan. Therefore, histological confirmation by needle biopsy sampling of the liver is necessary for a correct diagnosis of HHN. We report herein a case of benign HHN mimicking hepatocellular carcinoma in a 32-year-old male alcoholic liver cirrhosis patient without viral hepatitis infection. (Korean J Hepatol 2009; 15:193-200)

A case of Liver metastasis of gastric hepatoid adenocarcinoma
We report herein a case of hepatoid adenocarcinoma of the stomach with liver metastasis. Gastric carcinoma generally presents as adenocarcinoma and rarely shows a hepatoid pattern, which can produce alphafetoprotein (AFP). The stomach is one of the common sites at which hepatoid adenocarcinoma has been detected. A 75-year-old female patient was admitted to the hospital with a symptom of epigastric discomfort. Gastrofibroscopy revealed a large tumor occupying the greater curvature of the stomach body. The level of serum AFP was markedly increased. Abdominal computed tomography revealed multiple liver masses. Biopsy samples of the gastric lesion and liver masses finally confirmed her case as hepatoid adenocarcinoma in the stomach with liver metastasis. The AFP-producing gastric carcinoma needs special attention because it often presents with early liver metastasis and has a poor prognosis. (Korean J Hepatol 2009;15:201-208)

Development of ocular myasthenia during pegylated interferon and ribavirin treatment for ...
A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) α-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient’s ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN α -2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN α-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy. (Korean J Hepatol 2009;15:209-215)

Primary angiosarcoma of the Liver

Jae Yeon Seok , Young Bae Kim

Epithelioid hemangioendothelioma

Won Jae Lee

The Korean Journal of Efficacy and safety of sorafenib in patients with advanced hepatocellular ...

Jeong Heo
Background: Most cases of hepatocellular carcinoma occur in the Asia-Pacific region, where chronic hepatitis B infection is an important aetiological factor. Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important. We did a multinational phase III, randomised, double-blind, placebocontrolled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced (unresectable or metastatic) hepatocellular carcinoma. Methods: Between Sept 20, 2005, and Jan 31, 2007, patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A, were randomly assigned to receive either oral sorafenib (400 mg) or placebo twice daily in 6-week cycles, with efficacy measured at the end of each 6-week period. Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread (or both), Eastern Cooperative Oncology Group performance status, and geographical region. Randomisation was done centrally and in a 2:1 ratio by means of an interactive voice-response system. There was no predefined primary endpoint; overall survival, time to progression (TTP), time to symptomatic progression (TTSP), disease control rate (DCR), and safety were assessed. Efficacy analyses were done by intention to treat. This trial is registered with Clinical- Trials.gov, number NCT00492752. Findings: 271 patients from 23 centers in China, South Korea, and Taiwan were enrolled in the study. Of these, 226 patients were randomly assigned to the experimental group (n=150) or to the placebo group (n=76). Median overall survival was 6.5 months (95% CI 5.56-7.56) in patients treated with sorafenib, compared with 4.2 months (3.75-5.46) in those who received placebo (hazard ratio [HR] 0.68 [95% CI 0.50-0.93]; P=0.014). Median TTP was 2.8 months (2.63-3.58) in the sorafenib group compared with 1.4 months (1.35-1.55) in the placebo group (HR 0.57 [0.42-0.79]; P=0.0005). The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were hand-foot skin reaction (HFSR; 16 patients [10.7%]), diarrhoea (nine patients [6.0%]), and fatigue (five patients [3.4%]). The most common adverse events resulting in dose reductions were HFSR (17 patients [11.4%]) and diarrhoea (11 patients [7.4%]); these adverse events rarely led to discontinuation. Interpretation: Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region, and is well tolerated. Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment Randomised Protocol (SHARP) trial, sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma.

2009 EASL Highlights : Topics related to hepatitis B

In Kyoung Kim

2009 EASL Highlights : Topic related to the therapy of hepatitis B

Young Seok Kim

2009 EASL Highlights : Topics related to hepatitis C

Byung Seok Lee

2009 EASL Highlights : Topics related to the therapy of hepatitis C

Jeong Heo

2009 EASL Highlights : Topics related to hepatic fibrosis

Jong In Yang

2009 EASL Highlights : Topics related to Liver cirrhosis (variceal bleeding, portal ...

June Sung Lee — Sat, 01 Jan 2000 00:00:01 +0100

2009 EASL Highlights : Topics related to Liver cirrhosis (ascites and hepatorenal syndrome in ...

Gab Jin Cheon

2009 EASL Highlights : Topics related to hepatocellular carcinoma

Jae Seok Hwang

2009 EASL Highlights : Topics related to the treatment of hepatocellular carcinoma

Hyun Young Woo

2009 EASL Highlights : Topics related to nonalcoholic fatty Liver disease

Joon Ho Moon

2009 EASL Highlights : Topics related to alcoholic Liver disease

Jin Dong Kim

Inhibition of hepatitis B virus replication by RNA interference

Yun Gyu Park
.

Genetic epidemiological study on single nucleotide polymorphisms associated with hepatocellular ...

Yoon Jun Kim , Hyo Suk Lee — Sat, 01 Jan 2000 00:00:01 +0100
Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) as an etiologic agent in 80% of cases, and is the major cause of death among HBV carriers. Family history of HCC is a known risk factor for the development of HCC among chronically HBV infected patients, therefore, genetic factors are likely to modify the risk of HCC. However, the genetic factors that determine progression to HCC remain mostly to be recovered. It is estimated that there are millions of single nucleotide polymorphisms (SNPs) within human genome and they are likely to explain much of the genetic diversity of individuals. In this review, the natural history of HBV infection and host genetic factors related to HCC, study design and target gene selection for the detection of SNPs related to the occurrence of HCC were discussed. Also, several SNPs or haplotypes, which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection, were reviewed. Especially, recent studies in Korea, one of the HBV endemic areas, were discussed. Screening of these polymorphisms might be useful in clinical practice to stratify the lower or higher risk group for HCC and might modify the design of HCC surveillance programs in patients with chronic HBV infection, if further genetic susceptibilities are identified. The ongoing studies of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HCC, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies. (Korean J Hepatol 2008;15:7-14)

Inhibition of in vitro hepatitis B virus replication by Lentivirus-mediated short-hairpin RNA ...
Backgrounds/Aims: Hepatitis B virus (HBV) replicates via RNA intermediates, which could serve as targets for RNA interference (RNAi). Vector-mediated short-hairpin RNA (shRNA) can induce sustained RNAi in comparison to small interfering RNA. Lentiviral vector is known to induce prolonged RNAi with high transduction efficiency. In this study, we sought to test the in vitro efficacy of shRNA delivered by a lentiviral vector in suppressing the replication of HBV. Methods: Two shRNA sequences against the hepatitis B viral protein HBx (sh1580 and sh1685) were cloned downstream of the U6 promoter in an HIV-based plasmid to generate third-generation lentiviral vectors. HepAD38 cells were transduced with anti-HBx lentiviral vectors, and HBV replication was induced for 5 days. HBV DNA was isolated and quantified using real-time PCR. Results: Lentiviral vectors encoding the shRNA against HBV transduced HepAD38 cells with high efficacy. The total intracellular HBV DNA content was significantly reduced by both sh1580 and sh1685 (2.9% and 12.0%, respectively; P<0.05). HBV covalently closed circular DNA (cccDNA) was also suppressed significantly (19.7% and 25.5%, respectively; P<0.05). Conclusions: Lentivirus-mediated delivery of shRNA against HBx can effectively suppress the replication of HBV and reduce HBV cccDNA in cell culture systems. (Korean J Hepatol 2008;15:15-24)

Analysis of the cost-effectiveness of antiviral therapies in chronic hepatitis B patients in Korea
Backgrounds/Aims: The purpose of this study was to evaluate the cost-effectiveness of 1 year and up to 5 years of antiviral treatment for chronic hepatitis B (CHB). Methods: Two ten-health-state Markov models were developed for CHB patients. The proportion of patients remaining alive in each health state, and healthcare costs and quality-adjusted life years (QALYs) were determined during annual cycles of these Markov models. The total healthcare costs, life years, and QALYs over the 40-year time horizon of the model were calculated. The perspectives of the cost-effectiveness analysis were the Korean healthcare system and the healthcare needs of the CHB patient. Results: Short-course therapy with α-interferon or 1-year treatment with pegylated interferon α-2a, lamivudine (LMV), or adefovir (ADV) had limited impact on disease progression. In contrast, either LMV-ADV or ADV-LMV as rescue medication administered for 5 years resulted in a more sustained decrease in the rate of disease progression. The cost-effectiveness threshold in Korea was estimated to be approximately 25,000,000 South Korean won. LMV administered for 1 year is cost-effective in comparison with no treatment for both HBeAg-positive and HBeAg-negative CHB patients, but longer duration antiviral therapies administered for up to 5 years in CHB patients were found to be highly cost-effective by international standards. Conclusions: Antiviral treatment of CHB with LMV or ADV for up to 5 years using the alternative antiviral agent as rescue medication appears to be a cost-effective strategy for both HBeAg-positive and HBeAg-negative CHB patients in Korea. Economic evaluation of antiviral therapies should be studied further and updated, particularly for newer agents. (Korean J Hepatol 2008;15: 25-41)

The usefulness of transient elastography to diagnose cirrhosis in patients with alcoholic Liver ...

Sat, 01 Jan 2000 00:00:01 +0100
Backgrounds/Aims: It is not easy to differentiate between patients with cirrhosis and those with alcoholic liver disease. Liver biopsy is generally considered the gold standard for assessing hepatic fibrosis; however, this protocol frequently carries a risk of severe complications and false-negative results. Transient elastography (Fibroscan, Echosens, Paris, France), which is a noninvasive method of measuring liver stiffness, has become available for assessing liver fibrosis. Liver stiffness reportedly differs markedly with the cirrhosis etiology. The aim of this study was thus to determine the diagnostic accuracy of the Fibroscan in the detection of cirrhosis in patients with alcoholic liver disease. Methods: We enrolled 45 patients with alcoholic liver disease. Fibroscan, abdominal ultrasonography, aspartate aminotransferase/platelet ratio index (APRI), and liver biopsy were performed on all patients. Fibrosis stage was assessed using the Batts-Ludwig scoring system. Results: The stage of fibrosis (F1-F4) was distributed among the cohort as follows: 5 patients at F1, 4 patients at F2, 7 patients at F3, and 29 patients at F4. Liver stiffness differed significantly between each fibrosis stage (P<0.001). For the diagnosis of cirrhosis, the area under the receiver operating characteristic curve was 0.97 for transient elastography (95% confidence interval, CI, 0.93-1.01), 0.81 for ultrasonography (95% CI, 0.68-0.94), and 0.83 for APRI score (95% CI, 0.70-0.95). The optimal cut-off value of liver stiffness for detecting cirrhosis was 25.8 kPa, with a sensitivity of 90% and a specificity of 87%. Conclusions: Transient elastography is a useful method for diagnosing cirrhosis in patients with alcoholic liver disease. (Korean J Hepatol 2008;15:42-51)

Virologic response to adefovir dipivoxil monotherapy is not durable in HBeAg-positive, ...
Backgrounds/Aims: It has been shown that adefovir dipivoxil is an effective antiviral agent in the treatment of chronic hepatitis B (CHB), not only in wild-type hepatitis B virus (HBV) infection, but also in lamivudine-resistant (LAMV-R) cases. However, little is known about the durability of the virologic response to adefovir in LAMV-R CHB patients. Methods: Fifteen HBV e-antigen (HBeAg)-positive, LAMV-R CHB patients showed a virologic response to adefovir monotherapy. These patients received additional adefovir for at least a further 12 months. The virologic relapse rate after discontinuation of adefovir was evaluated. In addition, predictive factors associated with virologic relapse were investigated. Results: The median level of serum HBV DNA before adefovir administration was 7,457,840 IU/mL (range 107,920-99,524,960 IU/mL). The median duration of adefovir treatment was 30 months (range 14-46 months). During a median follow-up period of 14 months after discontinuation of adefovir, the 1-, 2-, 3-, 6-, and 12-month cumulative relapse rates were 26.7%, 53.3%, 73.3%, 80%, and 80%, respectively. High pretreatment HBV DNA levels were found to be the only factor that was predictive of off-therapy relapse. Conclusions: Our data suggest that the adefovir-monotherapy-induced virologic response is not durable in most patients with LAMV-R HBeAg-positive CHB, especially in those with a high pretreatment HBV DNA level. (Korean J Hepatol 2008;15:52-58)

The value of serum retinol-binding protein 4 Levels for determining disease severity in ...
Backgrounds/Aims: Serum retinol-binding protein 4 (RBP4) is known to be a specific transport protein for retinol, and has recently been reported to be associated with insulin resistance. Hyaluronic acid (HA) is a well-known marker of liver fibrosis. In this study, the degree to which serum RBP4 levels can be used to predict disease severity in patients with chronic liver disease (CLD) was evaluated. Methods: Serum levels of RBP4 and HA were measured in 573 CLD patients [235 with chronic hepatitis (CH), 230 with liver cirrhosis Child-Pugh grade (Child) A, and 108 with liver cirrhosis with Child B and C] and 40 normal controls. Results: The mean age of the whole cohort was 53.1 years and the causes of CLD were hepatitis B virus (61.9%), hepatitis C virus (9.8%), alcohol (9.0%), and nonalcoholic steatohepatitis (3.8%). Serum levels of RBP4 significantly reduced and HA increased with disease condition, from none (normal controls) to advanced cirrhosis (normal control: RBP4 4.3±0.1 mg/dL, HA 25.3±28.1 ng/mL; CH: RBP4 3.6±0.1 mg/dL, HA 75.5±7.8 ng/mL; cirrhosis with Child A: RBP4 2.6±0.1 mg/dL, HA 184.4±14.5 ng/mL; and cirrhosis with Child B and C: RBP4 1.6±0.1 mg/dL, HA 656.5±86.7 ng/mL; P<0.001, respectively). Serum RBP4 level was a distinguishing factor at the early stage of CLD between CH and Child A cirrhosis (post-hoc test; P<0.001) and was correlated with histological fibrosis score (n=80, P<0.05) and several biochemical factors. Antiviral therapy (n=45, median interval 1,205 days) resulted in an improvement in serum RBP4 levels (P=0.001). Conclusions: The results of our study suggest that RBP4 is a serologic marker for disease severity in patients with CLD. It could also be useful as an early marker of CLD and of the relative success of antiviral therapy. (Korean J Hepatol 2008;15:59-69)

Durability of a sustained virologic response in combination therapy with ...
Backgrounds/Aims: The ultimate goal of antiviral therapy using interferon/pegylated interferon combined with ribavirin in chronic C-viral hepatitis is to achieve a sustained virologic response (SVR). Several studies have shown that the reappearance rate of hepatitis C virus (HCV) RNA in serum after the achievement of an SVR is less than 1%; the durability of an SVR in Korean patients is not known. The aim of this study was to determine the durability of the virologic response in chronic hepatitis C patients with an SVR to antiviral therapy. Methods: A total of 156 patients who were treated successfully with interferon/peginterferon and ribavirin were evaluated retrospectively. Patients received either subcutaneous conventional interferon alpha 3×10(6) units three times a week or subcutaneous pegylated interferon (α-2a: 180 μg, α-2b: 80-100 μg) once a week in combination with ribavirin at 600-1,200 mg daily (depending on body weight). Patients with HCV genotype 1 were treated for 48 weeks, whereas those with non-genotype 1 were treated for 24 weeks. Results: Eighty-two patients underwent treatment with conventional interferon and ribavirin, whereas 74 patients were treated with pegylated interferon and ribavirin. An SVR was achieved in 73 patients (73/156, 46.8%). HCV RNA reappeared in eight patients (8/73, 11.0%, detected by qualitative PCR), including one patient with persistent viremia (1/73, 1.4%). Conclusions: Reappearance of HCV RNA after earlier achievement of an SVR might appear more frequently than previously reported. Close follow-up of these patients is recommended and the implication of temporary viremia should be determined in the future. (Korean J Hepatol 2008;15:70-79)

A case of hepatocellular carcinoma invading the gallbladder misdiagnosed as a primary ...
Extrahepatic metastasis of hepatocellular carcinoma (HCC) is occasionally seen in the lung, bone, adrenal gland, and lymph nodes. It is well known that HCC sometimes invades the biliary system. Since there is no peritoneum between the gallbladder and the liver fossa, a gallbladder cancer easily invades the liver; however, HCC seldom invades the gallbladder because it rarely destroys the muscle layer or the collagen fibers of the gallbladder wall. Routes of gallbladder metastasis of HCC include direct invasion, extension to the biliary system, and invasion of the adjacent hepatic vascular system. Some cases of gallbladder metastasis of HCC without direct invasion have been reported. We report here a case of HCC that directly invaded the gallbladder, and that resembled gallbladder carcinoma invading the liver. (Korean J Hepatol 2008;15:80-84)

A case of rhabdomyolysis during hospitalization for acute hepatitis A

Sat, 01 Jan 2000 00:00:01 +0100
A 29-year-old man was admitted to hospital with fever, myalgia, and sore throat. Initial laboratory findings were compatible with acute hepatitis; he was positive for the serologic marker for acute hepatitis A. On the 3rd day of admission, in spite of normalization of body temperature and a reduction in serum liver enzyme levels, serum levels of creatinine phosphokinase had increased up to 16,949 U/L. The patient recovered with supportive therapy and was discharged on the 12th day. We report a case of acute hepatitis A complicated by rhabdomyolysis during hospitalization. (Korean J Hepatol 2008;15:85-89)

A case of advanced hepatocellular carcinoma with portal vein tumor invasion controlled by ...
Portal vein invasion is a grave prognostic indicator in the setting of hepatocellular carcinoma (HCC). There is currently no effective method for preventing the invasion of HCC into the main portal vein. We report here a case of advanced HCC with portal vein tumor thrombosis that was effectively treated with percutaneous ethanol injection (PEI), having previously enabled subsequent successive transarterial chemoembolization (TACE). A 60-year-old male patient was diagnosed with a huge HCC, based on computed tomography and angiographic findings. Despite two sessions of TACE, the tumor invaded the right portal vein. PEI was performed on the malignant portal vein thrombosis, and three sessions thereof reduced the extent of tumor thrombi in the portal vein. Successive TACEs were performed to treat the HCC in the hepatic parenchyma. The patient was still living 19 months after the first PEI with no evidence of tumor recurrence, and his liver function remained well preserved. (Korean J Hepatol 2008;15:90-95)

Well differentiated hepatocellular carcinoma: Pathological diagnosis of needle biopsied Liver tissue

Jae Yeon Seok , Young Nyun Park
.

Angiosarcoma

Won Jae Lee
.

The Korean Journal of Treatment recommendations for chronic hepatitis B: an evaluation of ...

Neung Hwa Park
.

Treatment of chronic hepatitis C: Efficacy of initial treatment of peginterferon alpha-2a ...

Youn Jae Lee

Hepatitis B virus genetic diversity and mutant

Hyung Joon Yim
Hepatitis B virus (HBV) is a partially double stranded DNA virus with genetic diversity represented by eight genotypes (A to H). Natural course and response to treatment could be affected by HBV genotypes. HBV shows high rates of turn over in the absence of proof-reading ability. As a result, large amounts of quasi-species are produced naturally or antiviral-associated. HBV consists of four open reading frames, namely preS/S gene, precore/core gene, polymerase gene, and X gene. Mutations on preS gene can result in undetectable HBsAg even in case that HBV is replicating. Surface gene mutation leads to decreased binding affinity to anti-HBs, which is associated with a vaccine escape mutant. Precore mutation abolishes HBeAg whereas mutations on basal core promoter gene down-regulate the HBeAg production. Mutations on basal core promoter are associated with increased HBV replication and high incidence of progressive liver diseases such as liver cirrhosis and hepatocellular carcinoma. Mutations on polymerase genes are often induced by antiviral therapy. Emergence of antiviral-resistant mutation is the major cause of treatment failure. Furthermore, existence of prior antiviral-resistant mutations limits the options of subsequent antiviral agents. Therefore, judicious use of antivirals and selection of the most potent drug with the lowest resistance rate are of the utmost importance for the prevention of antiviral-associated mutants. Detailed knowledge and understanding of HBV genetic diversity and mutant would be critical to establish strategies for the diagnosis and management of HBV infection. (Korean J Hepatol 2008;14:446-464)

Changes in liver stiffness during the course of acute hepatitis A
Backgrounds/Aims: In some patients with chronic hepatitis, liver stiffness (LS) findings do not reflect fibrosis stage. This study was performed to evaluate whether acute liver inflammation could influence LS findings. Methods: Patients with acute hepatitis A admitted to our hospital were included. Hepatitis was classified on admission using serum ALT and bilirubin levels as inflammation phase, jaundice phase, or recovery phase. Patients who admitted during the recovery phase (whose ALT and bilirubin levels fell continuously during hospitalization) and therefore, their peak-ALT and peak bilirubin levels could not be determined were exduded. Enrolled patients underwent FibroScan during hospitalization and after discharge. Results: Seventy-six patients with acute hepatitis A were enrolled (median age, 29 years; 46 men and 30 women). Among them, 33 (43.4%) and 43 (56.6%) patients were admitted during the inflammation phase and jaundice phase, respectively. For patients admitted during the inflammation phase, mean (±SD) time from symptom-onset day to maximum ALT level was 7 (±3) days. For all patients, mean time from symptom-onset to maximum bilirubin level was 11 (±4) days. Mean LS during admission was 8.9 (±3.3) kPa (median, 8.4 kPa). LS was significantly correlated with serum bilirubin level, which was the only factor found to be significantly associated with the increased LS (>7.08 kPa). In all patients, LS increased gradually from the symptom-onset and peaked at 8-9 days later. Conclusions: Severe hepatic inflammation can affect the LS findings and thus, care is required when assessing fibrosis stage using LS measurement in patients with severe inflammation. (Korean J Hepatol 2008;14:465-473)

Clinical outcomes and predictive factors of spontaneous survival in patients with fulminant ...

Jwa Min Kim , Yoon Seon Lee , Jae Ho Lee , Won Kim , Kyung Soo Lim
Backgrounds/Aims: The occurrence of acute hepatitis A is increasing and its progression to fulminant hepatic failure (FHF) is frequent. We investigated the frequency and clinical outcomes of fulminant hepatitis A and also analyzed the predictive factors of spontaneous survival. Methods: A total of 568 patients presented with acute hepatitis A from January 2003 to June 2008, of which the 35 (6.2%) patients with FHF were divided into two groups: spontaneous survival and transplant/death. These two groups were compared according to various clinical features including the MELD score and King`s College Hospital (KCH) criteria. Results: The rate of FHF development increased over time among patients with acute hepatitis A: 0% in 2003, 3.4% in 2004, 3.2% in 2005, 6.0% in 2006, 7.7% in 2007, and 13.0% in 2008. Twenty patients (57.1%) showed spontaneous survival, 13 (37.1%) received liver transplantation, and 5 (14.3%) died during hospitalization. The two groups of spontaneous survival (N=20) and transplant/death (N=15) showed significant differences in prothrombin time at admission and at its worst value, albumin at its worst value, and hepatic encephalopathy grade at admission and at its worst value. The MELD score was lower in the spontaneous-survival group than in the transplant/death group (27.0±7.8 vs. 37.0±7.1, mean±SD; P=0.001). However, KCH criteria did not differ significantly between the two groups. On multivariate analysis, HEP grade was the only significant predictive factor, being negatively correlated with spontaneous survival (OR=0.068, P=0.025). Conclusions: FHF due to hepatitis A has increased in recent years, and in our cohort the HEP grade was closely associated with spontaneous survival. (Korean J Hepatol 2008;14:474-482)

Clinical characteristics of 159 cases of acute toxic hepatitis

Sat, 01 Jan 2000 00:00:01 +0100
Backgrounds/Aims: Toxic hepatitis has recently been discovered to be a major cause of acute hepatitis. We studied the clinical features and prognosis of patients diagnosed with toxic hepatitis at a single institution. Methods: A retrospective analysis was performed using medical records of 159 cases of toxic hepatitis that were diagnosed from March 2003 to March 2008. Patients were selected based on a RUCAM score of 4 or above. Results: The incidence was higher in women (n=97) than in men (n=62). The age (mean±SD) of the patients was 51±15 years. The major causes of the disease included the use of Korean traditional therapeutic preparations (34.0%), herbal medicines (41.5%), and drugs prescribed by a physician (23.9%). At the time of admission, jaundice was the most common symptom (41.5%), and the results of a liver serum battery were as follows: aspartate aminotransferase, 729.4±877.0 IU/L; alanine aminotransferase, 857.1±683.0 IU/L; total bilirubin, 6.4±6.5 mg/dL; and alkaline phosphatase, 209.8±130.0 IU/L. The hospitalization period was 10.0±9.5 days, and the duration of recovery from liver injury was 31.0±29.5 days. The factors associated with the hospitalization period included the presence of anorexia and the serum levels of albumin and bilirubin at the time of admission (P<0.05). A high serum bilirubin level and a history of alcohol ingestion were associated with a delayed recovery (P<0.05). The sex, age, BMI, and duration of medication were not significantly related to the hospitalization and recovery periods. Conclusions: The main cause of acute toxic hepatitis in the current study was the use of herbal medicines. The severity of liver injury at the time of admission was a major factor significantly associated with the hospitalization and recovery periods. (Korean J Hepatol 2008;14:483-492)

Efficacy of initial treatment with peginterferon alpha-2a versus peginterferon alpha-2b in ...
Backgrounds/Aims: Peginterferon alpha-2a or -2b is the standard treatment regimen in chronic hepatitis C. However, there have been few comparative studies of the efficacies of these two types of peginterferon. We evaluated their efficacies in combination with ribavirin as a initial treatment for chronic hepatitis C. Methods: Ninety-seven patients were treated with peginterferon alpha-2a (180 ?g/week, n=48) or peginterferon alpha-2b(1.5 ?g/kg/week, n=49) plus ribavirin (800 mg/day for 24 weeks in genotype non-1 or 1,000-1,200 mg/day for 48 weeks in genotype 1). Virologic responses including the early virologic response (EVR), end-of-treatment response (ETR), sustained virologic response (SVR), and adverse effects were analyzed retrospectively. Results: The virologic response rates did not differ significantly between peginterferon alpha-2a and -2b: 89.6% and 89.7% for EVR, 79.2% and 79.5% for ETR, 72.9% and 73.5% for SVR, respectively. Analysis of the virologic responses according to genotype also revealed no significant differences in SVR between peg-interferon alpha-2a and -2b (59.3% vs. 59.7% for genotype 1 and 90.5% vs. 83.3% for genotype non-1, respectively), or in adverse effects including flu-like symptom, rash, itching, neutropenia, and thrombocytopenia. Conclusions: We found no significant differences in therapeutic efficacies and adverse effects between the alpha-2a and -2b types of peginterferon as the initial treatment regimen in naive chronic hepatitis C patients. (Korean J Hepatol 2008;14:493-502)

The efficacy of adefovir dipivoxil monotherapy and the incidence of genotypic resistance to ...
Background/Aims: Adefovir dipivoxil (ADV) is a nucleotide analogue that inhibits wild-type hepatitis B virus (HBV) and lamivudine (LMV)-resistant HBV mutants. The aim of this study was to elucidate the efficacy of ADV monotherapy and the incidence of genotypic resistance to ADV in patients with LMV-resistant chronic HBV infection. Methods: This study involved 124 patients with chronic HBV infection who had received ADV monotherapy due to the presence of LMV-resistant HBV mutants. The efficacy of ADV was evaluated by the normalization of serum alanine aminotransferase (ALT) level and by the reduction of serum HBV DNA level (with cutoff levels of 2×10⁴ IU/mL and 2×10² IU/mL). The cumulative rate of HBeAg loss or seroconversion was assessed in HBeAg-positive patients. The development of mutations in the reverse trancriptase region of HBV DNA polymerase was evaluated by direct sequencing analysis during ADV monotherapy. Results: The mean serum HBV DNA level was 5.94 log10IU/mL. At 12 and 24 months after ADV monotherapy, the cumulative rates of serum ALT normalization were 69.4% and 75.5%, respectively, and those of serum HBV DNA reduction were 79.8% and 89.2% for a cutoff level of 2×10⁴ IU/mL, and 44.2% and 59.0% for a cutoff of 2×10² IU/mL. The mean serum HBV DNA levels at 12 and 24 months were significantly lower than baseline, at 3.24 and 3.04 log10IU/mL, respectively (P<0.001). At 12 months after ADV treatment, the cumulative rates of HBeAg loss and seroconversion were 15.8% and 10.5%, respectively, and the rtN236T and rtA181T/V mutants in HBV DNA polymerase were identified in 25% and 64% of patients, respectively. Conclusions: Although ADV monotherapy is effective, it leads to a high rate of mutations of HBV DNA reverse transcriptase gene in patients with chronic HBV infections who have LMV-resistant HBV mutants. (Korean J Hepatol 2008;14:503-512)

A case report of treatment with pegylated interferon alpha for Lamivudine-resistant chronic ...
The wide use of lamivudine in chronic hepatitis B has produced a monotonic increase in patients with lamivudine resistance. Therefore, treating lamivudine resistance in chronic hepatitis B is a major concern in clinical practice for the treatment of hepatitis B virus (HBV). There is conflicting evidence on the outcome of pegylated interferon alpha (PEG-IFN α) therapy against lamivudine-resistant HBV, which is due to mutations in the YMDD motif. We experienced a patient with chronic hepatitis B who was successfully treated with PEG-IFN α-2a after the development of virologic and biochemical breakthrough during lamivudine therapy. Virologic breakthrough was associated with the emergence of YMDD mutants 48 months after starting lamivudine therapy. Treatment with PEG-IFN α-2a for 12 months resulted in an undetectable serum level of HBV DNA and the resolution of hepatitis, and the virologic response was maintained over 16 months after cessation of PEG-IFN α-2a. (Korean J Hepatol 2008;14:513-518)

Treatment with pegylated interferon and ribavirin in a patient with fibrosing cholestatic ...
Fibrosing cholestatic hepatitis (FCH) is the most devastating manifestation of recurrent hepatitis C in transplant recipients with hepatitis C virus (HCV), possibly leading to death or retransplantation. Although FCH was first described as a complication of hepatitis B, this manifestation has been well documented in association with HCV in the setting of liver transplantation, bone marrow transplantation, heart transplantation, and end-stage human immunodeficiency virus infection. We report the clinical course and antiviral response in a patient with FCH due to recurrent hepatitis C after cadaveric liver transplantation who was treated with pegylated interferon α-2a and ribavirin. (Korean J Hepatol 2008;14:519-524)

A case of hepatic epithelioid hemangioendothelioma that caused extrahepatic metastases without ...
Epithelioid hemangioendothelioma is a neoplasm of vascular origin with a low-to-intermediate malignant potential and is one of the rare sarcomas arising from the liver. Its etiology is unknown and its clinical outcome is unpredictable. There is no generally accepted therapeutic strategy because of its rarity and the variable natural course between hemangioma and angiosarcoma. We report a case of a 64-year old woman who underwent hepatic resection due to epithelioid hemangioendothelioma in the right lobe that progressed to extrahepatic metastases of the bone, pleura, and peritoneum 22 months later. However, after resection there was no primary hepatic recurrence. (Korean J Hepatol 2008;14:525-531)

Mucin hypersecreting cholangiocarcinoma

Yoon Mi Jeen , So Young Jin

Focal nodular hyperplasia-Like nodule

Won Jae Lee

The Korean Journal of Risk factors for mortality after surgery in patients with cirrhosis

Joon Hyeok Lee
Background & Aims: Current methods of predicting risk of postoperative mortality in patients with cirrhosis are suboptimal. The utility of the Model for End-stage Liver Disease (MELD) in predicting mortality after surgery other than liver transplantation is unknown. The aim of this study was to determine the risk factors for postoperative mortality in patients with cirrhosis. Methods: Patients with cirrhosis (N=772) who underwent major digestive (n=586), orthopedic (n=107), or cardiovascular (n=79) surgery were studied. Control groups of patients with cirrhosis included 303 undergoing minor surgical procedures and 562 ambulatory patients. Univariate and multivariable proportional hazards analyses were used to determine the relationship between risk factors and mortality. Results: Patients undergoing major surgery were at increased risk for mortality up to 90 days postoperatively. By multivariable analysis, only MELD score, American Society of Anesthesiologists class, and age predicted mortality at 30 and 90 days, 1 year, and long-term, independently of type or year of surgery. Emergency surgery was the only independent predictor of duration of hospitalization postoperatively. Thirty-day mortality ranged from 5.7% (MELD score, <8) to more than 50% (MELD score, >20). The relationship between MELD score and mortality persisted throughout the 20-year postoperative period. Conclusions: MELD score, age, and American Society of Anesthesiologists class can quantify the risk of mortality postoperatively in patients with cirrhosis, independently of the procedure performed. These factors can be used in determining operative mortality risk and whether elective surgical procedures can be delayed until after liver transplantation.

2008 AASLD Highlights : Topics related to hepatitis B

Jae Youn Cheong

2008 AASLD Highlights : Topics related to the therapy of hepatitis B

Byoung Kuk Jang

2008 AASLD Highlights : Topics related to virology and pathogenesis of hepatitis C

Kang Mo Kim

2008 AASLD Highlights : Topics related to the therapy of hepatitis C

Jong Ryul Eun

2008 AASLD Highlights : Topics related to Liver fibrosis

Moon Young Kim — Sat, 01 Jan 2000 00:00:01 +0100

2008 AASLD Highlights : Topics related to liver cirrhosis and its complications (1)

Yeon Seok Seo

2008 AASLD Highlights : Topics related to liver cirrhosis and its complications (2)

Byung Seok Kim

2008 AASLD Highlights : Topics related to hepatocellular carcinoma

Soung Won Jeong

2008 AASLD Highlights : Topics related to treatment of Liver cancer

Yoon Jun Kim

2008 AASLD Highlights : Topics related to non-alcoholic fatty Liver disease

Dong Hee Kim

2008 AASLD Highlights : Topics related to alcoholic Liver disease

Jun Yong Park

Anti-tumor mechanisms and regulation of survivin by selective cyclooxygenase-2 inhibitor

Jeong Won Jang

Clinical application of stem cells in Liver diseases

Si Hyun Bae
Most liver diseases lead to hepatic dysfunction with organ failure. Liver transplantation is the best curative therapy, but it has some limitations such as donor shortage, possibility of rejection, and maintenance of immunosuppressant. New therapies have been actively searched for over several decades, primarily in the form of artificial liver support devices and hepatocyte transplantation, but both of these modalities remain experimental. Stem cells have recently shown promise in cell therapy because they have the capacity for self-renewal and multilineage differentiation, and are applicable to human diseases. Very recent reports of unexpected plasticity in adult bone marrow have raised hopes of stem cell therapy offering exciting therapeutic possibilities for patients with chronic liver disease. Both rodent and human embryonic stem cells, bone marrow hematopoietic stem cells, mesenchymal stem cells, umbilical cord blood cells, fetal liver progenitor cells, adult liver progenitor cells, and mature hepatocytes have been reported to be capable of self-renewal, giving rise to daughter hepatocytes both in vivo and in vitro. These cells can repopulate livers in animal models of liver injury and appear to be able to improve liver function. However, significant challenges still exist before these cells can be used in humans, such as the lack of consensus about the immunophenotype of liver progenitor cells, uncertainty of the physiological role of reported candidate stem/progenitor cells, practicality of obtaining sufficient quantity of cells for clinical use, and concerns over ethics, long-term efficacy, and safety. There have been reports of phase 1 trials using stem cell transplantation in humans for liver diseases, but more effective trials are needed. We review the use of stem cells (focusing on adult ones) and the reported human clinical trials, and highlight the challenges facing clinicians in their quest to use liver stem cells to save lives. (Korean J Hepatol 2008;14:309-317)

Effects of pegylated interferon and ribavirin in Korean patients with chronic hepatitis C virus ...
Background/Aims: We assessed the efficacy and safety of pegylated interferon (peginterferon) plus ribavirin and identified the predictors of a sustained virologic response (SVR) in Korean patients with chronic hepatitis C virus infection. Methods: A total of 192 patients with chronic hepatitis C, treated with both peginterferon (n=141) or conventional interferon (n=51) and ribavirin, were analyzed retrospectively. Peginterferon alfa-2a (180 μg/week) or -2b (1.5 μg/kg/week) or interferon alfa-2a (3 MIU thrice weekly) was administered in combination with ribavirin at 1,000-1,200 mg/day for 48 weeks for genotype 1 and at 800 mg/day for 24 weeks for genotypes 2 and 3. Results: The overall SVR rate was 80.9% (114/141) in the peginterferon group and 52.9% (27/51) in the interferon group (P=0.0001). The SVR rate in genotype 1 was 69.5% (41/59) in the peginterferon group and 31.6% (6/19) in the interferon group (P=0.0033), whereas in genotype 2 or 3 it was 89.0% (73/82) in the peginterferon group and 65.6% (21/32) in the interferon group (P=0.0032). The predictors of SVR in the peginterferon group were genotype, absence of cirrhosis, and early virologic response (P<0.05). Conclusions: In Korean patients with chronic hepatitis C, a regimen of peginterferon and ribavirin was more effective than a regimen of conventional interferon and ribavirin. This result is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C. (Korean J Hepatol 2008;14: 318-330)

Natural history of gastric varices and risk factors for bleeding
Background/Aims: Gastric varices (GV) are one of the most serious complications of portal hypertension, but there is limited information on the clinical course of GV in Korea. The aim of this study was to elucidate the natural history of GV bleeding in Korean patients. Methods: Of 604 patients with GV diagnosed between May 1995 and May 2005 at the Samsung Medical Center, 237 patients without a history of variceal bleeding or previous intervention for varices were investigated. The cumulative incidence rates of GV bleeding, long-term survival rates, and risk factors for GV bleeding were evaluated. Results: The cumulative incidence rates of GV bleeding were 4.8%, 19.9%, and 23.2% at 1, 3, and 5 years after diagnosis, respectively. The overall survival rates were 88.6%, 53.2%, and 37.2% at 1, 5, and 10 years. In the univariate analysis, fundal varices, large (F3) GV, red color sign, and poor liver function (Child-Pugh class B or C) were significant risk factors for GV bleeding. In the multivariate analysis, large GV (hazard ratio 2.49) and poor liver function (hazard ratio 3.95) were the independent risk factors. Conclusions: GV bleeding was more frequent in patients with fundal varices than in patients with type 1 gastroesophageal varices, and large GV and poor liver function were risk factors for GV bleeding. Close observation and prophylaxis for variceal bleeding might be warranted in high-risk patients. (Korean J Hepatol 2008;14:331-341)

Usefulness of Liver stiffness measurement for predicting the presence of esophageal varices in ...
Background/Aims: Bleeding from esophageal varices (EV) is a major cause of death in patients with liver cirrhosis. Endoscopic screening is recommended for diagnosing EV, but various noninvasive parameters can also be used to predict EV. The liver stiffness measurement (LSM), a noninvasive technique for estimating liver fibrosis, was recently reported to be strongly correlated with the hepatic venous pressure gradient. This study evaluated the usefulness of LSM for predicting the presence and size of EV in patients with cirrhosis. Methods: The relationships of LSM with the presence and size of EV were analyzed in 112 patients with liver cirrhosis. Liver cirrhosis was diagnosed histologically or clinically. The presence and size of EV were assessed by endoscopy, and LSM was determined by the FibroscanⓇ technique. Results: LSM was strongly correlated with the presence of EV (P<0.0001): the LSM value was 42.7±21.9 kPa (mean±standard deviation) in patients with EV (n=82) and 19.1±12.6 kPa in patients without EV (n=30). The area under the receiver operating characteristic curve was 0.818 (95% CI, 0.732-0.904) for predicting the presence of EV, and an LSM value of 19.7 kPa was predictive of the presence of EV with a sensitivity of 87%, a specificity of 70%, a PPV of 89%, and a NPV of 66%. However, there was a weak correlation between LSM and the size of EV. Conclusions: LSM is useful for predicting the presence of EV in patients with cirrhosis but not their size. (Korean J Hepatol 2008;14:342-350)

Down-regulation of survivin in growth inhibition of hepatoma cells induced by a selective ...
Background/Aims: Cyclooxygenase-2 (COX-2) inhibitors reportedly inhibit the growth of hepatocellular carcinoma (HCC) via caspase-dependent or caspase-independent apoptosis, which is due to COX-2 being associated with hepatocarcinogenesis. Survivin is highly expressed in most human cancers, but the mechanism regulating survivin expression remains unclear. We investigated the regulatory expression of survivin in selective-COX-2-inhibitor-induced growth inhibition of hepatoma cells. Methods: After treatment with NS-398 (a selective COX-2 inhibitor) at various concentrations (10, 50, 100, 150, and 200 μM), the growth inhibition of Hep3B hepatoma cells was assessed by an MTT cell-viability assay, DNA fragmentation gel analysis, and flow cytometry. The expression of survivin transcript was analyzed by reverse-transcription polymerase chain reactions. Results: NS-398 inhibited the growth of hepatoma cells by an amount dependent on the concentration and the time since treatment. Apoptotic DNA ladder and flow-cytometry shifting to the sub-G1 phase were revealed in NS-398-induced growth inhibition of hepatoma cells. NS-398 suppressed the expression of the survivin gene in a concentration- and time-dependent manner. Conclusions: Survivin was down-regulated in the growth inhibition of hepatoma cells induced by a selective COX-2 inhibitor, NS-398, in a concentration- and time-dependent manner. These results suggest the therapeutic inhibition of COX-2 via suppression of survivin in HCC. (Korean J Hepatol 2008;14:351-359)

Clinical outcomes of systemic chemotherapy in hepatocellular carcinoma patients with multiple ...
Background/Aims: Advanced hepatocellular carcinoma (HCC) with multiple lung metastases has a poor prognosis with no effective treatment having been established. This study evaluated the outcomes of systemic chemotherapy for advanced HCC with multiple lung metastases. Methods: Between January 2000 and December 2006, 68 patients were diagnosed with HCC presenting with multiple lung metastases. Sixteen patients in the terminal stage, such as Child-Pugh grade ‘C’ or an Eastern Cooperative Oncology Group performance status exceeding grade 2, were excluded from the analysis. The following treatment modalities were applied: 26 patients received primary tumor treatment (transarterial chemoembolization or intra-arterial chemotherapy) with systemic chemotherapy, 10 patients received primary treatment only, 8 patients received systemic chemotherapy only, and 8 patients received highly supportive care. The treatment responses and median survival times for the modalities were analyzed and compared. Results: The median age of the 52 analyzed patients (45 males) was 52.4 years. The most common etiology of HCC was chronic hepatitis B virus infection (n=44, 84.6%) followed by hepatitis C virus infection (n=2, 3.8%), with the etiology being unknown in 6 cases (11.5%). The treatment modality had no significant effect on the treatment response rate (P=0.432) or median survival time (133, 66, 74, and 96 days for primary tumor treatment with systemic chemotherapy, primary tumor treatment only, systemic chemotherapy only, and highly supportive care, respectively; P=0.067). Conclusions: We found that systemic chemotherapy was not effective in treating HCC presenting with multiple lung metastases. Improving the effectiveness of systemic treatment and selecting patients who would benefit from such treatment remains a major challenge. (Korean J Hepatol 2008;14:360-370)

Risk factors for early recurrence after surgical resection for hepatocellular carcinoma

Ui Jun Park, M.D., Yong Hoon Kim, M.D., Koo Jeong Kang, M.D., Tae Jin Lim, M.D.
Background/Aims: Early recurrence (ER) after liver resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aimed to identify the factors associated with ER after curative hepatic resection for HCC. Methods: From the July 2000 to July 2006, 144 patients underwent hepatic resection for HCC at a single institution. After excluding those with ruptured HCC, combined or mixed HCC, and who died during admission, 116 patients were analyzed. Patients with ER (defined as within 1 year) were compared with those who remained free of disease for more than 1 year. Various clinical characteristics including tumor and operative factors were evaluated to determine the factors predicting postoperative ER using univariate and multivariate analyses. Results: ER occurred in 51 patients (44%). In the univariate analysis, tumor size (P=0.001), microvascular invasion (P=0.003), portal vein invasion (P=0.001), TNM stage (P=0.010), serum levels of alpha-fetoprotein (AFP) (P=0.002) and aspartate aminotransferase (AST) (P=0.011), and operative time (P=0.033) were significantly associated with ER. AFP and AST were the independent predictors of ER in the multivariate analysis (P<0.05). Conclusions: Preoperative serum AFP and AST levels were the independent risk factors for ER after surgical resection for HCC. Close postoperative surveillance is recommended for early detection of recurrence and additional treatments in patients with these factors. (Korean J Hepatol 2008;14:371-380)

A case of severe hypophosphatemia related to adefovir dipivoxil treatment in a patient with ...

Heon Ju Lee , Tae Nyeun Kim , Jong Ryul Eun , Jae Won Choi
Adefovir dipivoxyl (ADV) effectively suppresses hepatitis B virus (HBV) replication but exhibits nephrotoxicity with severe hypophosphatemia when administered at a high dosage. This is the first report of severe hypophosphatemic osteomalacia induced by ADV at 10 mg/day. A 42-year-old man with HBV-related chronic liver disease presented with generalized bone pain, especially in the left ankle. He had been taking ADV for more than 1.5 years following a clinical breakthrough due to lamivudine-resistant HBV. Aggravating severe hypophosphatemia and elevated serum alkaline phosphatase levels with high bone fraction had been noted after 6 months of ADV therapy. Bone densitometry, simple bone X-rays, and a whole-body bone scan demonstrated osteoporosis and multiple areas with hot uptake, especially in the left ankle. All the image findings and symptoms improved after correcting the hypophosphatemia. (Korean J Hepatol 2008;14:381-386)

Three cases of multiple infracted regenerative nodules in Liver cirrhosis after ...

Byung Seok Kim , Chang Hyeong Lee
An infarction of regenerative nodules in liver cirrhosis is a rare abnormality characterized by their coagulative necrosis. We presume that ischemic necrosis is induced by a sudden reduction in the portal and arterial blood flows after blood loss or shock. Most patients with infarcted regenerative nodules have experienced previous episodes of gastrointestinal hemorrhage. Awareness of the entity of infarcted regenerative nodules and its inclusion in the differential diagnosis of multiple hepatic nodules in liver cirrhosis is important, particularly in patients with an episode of gastrointestinal bleeding. The possible difficulty of differentiating infarcted regenerative nodules in liver cirrhosis from hypovascular hepatocellular carcinoma by initial imaging findings alone means that a liver biopsy and serial imaging might be helpful in the differential diagnosis. We report three cases of multiple infarcted regenerative nodules in liver cirrhosis after gastrointestinal hemorrhage. (Korean J Hepatol 2008;14:387-393)

Hepatocellular carcinoma with Lymphoid stroma: report of two cases

Hye-Jeong Choi, M.D., Joon Hyuck Choi, M.D.1
We report two cases of hepatocellular carcinoma with prominent lymphocytic infiltration, which has been described as a subtype of hepatocellular carcinoma with good prognosis. One case showed lymphoid follicles and dense lymphocytic infiltrates within the tumor and its periphery, and the other case showed marked lymphocytic infiltration in the cancerous tissue. Piecemeal necrosis of cancer cells and atypical reactive changes were evident. The two cases were seronegative for hepatitis B surface antigen, antibody to hepatitis C virus, and Epstein-Barr virus DNA. One of the cases showed Clonorchis infestation. The prognostic significance of lymphocytic stroma in hepatocellular carcinoma requires further investigation. (Korean J Hepatol 2008;14:394-398)

Epithelioid hemangioendothelioma of the Liver

Young Bae Kim

Imaging findings of hepatic adenoma

Joon Koo Han , Hyo Won Eun , Se Hyung Kim

The Korean Journal of Entecavir 1 mg therapy for Lamivudine-refractory chronic hepatitis B

Hyung Joon Kim

2008 Asian-Pacific Hepatitis B Academy Highlights : Definitions and predictors for treatment ...

Soung Won Jeong

2008 Asian-Pacific Hepatitis B Academy Highlights : Long-term efficacy and safety of oral ...

Hyang Ie Lee

2008 Asian-Pacific Hepatitis B Academy Highlights : Oral antiviral therapy: management of resistance

Yong Jai Park

2008 Asian-Pacific Hepatitis B Academy Highlights : New antiviral drugs for chronic hepatitis B

Dae Hee Choi

2008 Asian-Pacific Hepatitis B Academy Highlights : Immune modulation in chronic hepatitis B

Jung Hyun Kwon

2008 Asian-Pacific Hepatitis B Academy Highlights : Health economics in the treatment of ...

Kyung Ah Kim

KASL Special Contribution : Problems faced by Korean patients with chronic liver disease and ...

Sat, 01 Jan 2000 00:00:01 +0100

The relation between hepatic venous pressure gradient and complications of liver cirrhosis

Yong Han Paik — Sat, 01 Jan 2000 00:00:01 +0100

Physiologic and pathologic experimental models for studying cholangiocytes

Seung Ok Lee
Cholangiocytes (epithelial cells lining the intra- and extrahepatic bile ducts) and hepatocytes are two major components of liver epithelia. Although cholangiocytes are less numerous than hepatocytes, they are involved in both bile secretion and diverse cellular processes such as cell-cycle phenomena, cell signaling, and interactions with other cells, matrix components, foreign organisms, and xenobiotics. Cholangiocytes are also targets in several human diseases including cholangiocarcinoma, primary sclerosing cholangitis, autoimmune cholangitis, and vanishing bile-duct syndrome. The rapid advances in experimental biology technologies are greatly expanding interest in and knowledge of the physiology and pathophysiology of cholangiocytes. This review focuses on the progress of in vivo and in vitro experimental models in elucidating the physiologic functions of cholangiocytes and the pathophysiology of various cholangiopathies. The following aspects are reviewed: isolation of cholangiocytes from the liver and their heterogeneity, various culture systems, establishment of cholangiocyte cell lines, isolation and usage of intrahepatic bile-duct units, three-dimensional modeling of the bile duct, experimental models for inducing cholangiocyte proliferation, and various cholangiopathies such as cholangiocarcinoma, primary sclerosing cholangitis, and autoimmune cholangitis. (Korean J Hepatol 2008;14:139-149)

Measurement of hepatic venous pressure gradient in Liver cirrhosis: Relationship with the ...
Background/Aims: The relationships between the hepatic venous pressure gradient (HVPG) and the status of cirrhosis, complications of portal hypertension and the severity of cirrhosis are not clear. The aim of this study was to determine the relationships between HVPG and the complications or status of cirrhosis. Methods: The HVPG, gastroesophageal varices, Child-Pugh score, Model for End-Stage Liver Disease (MELD) score, presence of ascites, recent bleeding history and the status of cirrhosis were assessed in a cohort of 172 patients (156 males, 16 females) with liver cirrhosis. Results: The HVPG was 15.6±5.1 (mean± SD) mmHg (4-33 mmHg) and was significantly higher in patients in the decompensated stage than in those in the compensated stage (16.6±4.3 vs. 10.8±6.1 mmHg, respectively; P<0.01). HVPG was higher in bleeders than in nonbleeders (16.9±4.5 vs. 12.8±5.3 mmHg, respectively; P<0.01), and in patients with ascites than in those without ascites (16.4±4.1 vs. 14.5±6.2 mmHg, respectively; P<0.05). HVPG was significantly lower in the presence of gastric varices than in their absence (14.0±3.4 vs. 16.0±5.3 mmHg, respectively; P<0.05); however, no significant correlation was detected between HVPG and the grade of esophageal varices (P>0.05). HVPG was significantly higher in Child’s B cirrhosis (n=87, 15.6±4.7 mmHg) and Child’s C cirrhosis (n=36, 18.4±4.7 mmHg) than in Child’s A cirrhosis (n=49, 13.7±5.1 mmHg; P<0.01). HVPG also was strongly correlated with the MELD score (P<0.01). The time required to measure the HVPG was 11.2±6.4 min, and only three cases of minor complication occurred during the procedure. Conclusions: HVPG was correlated with the severity of liver cirrhosis, presence of ascites, and risk of variceal bleeding in patients with liver cirrhosis. (Korean J Hepatol 2008;14:150-158)

Serum hyaluronic acid Level: Correlation with quantitative measurement of hepatic fibrosis in a ...

Sat, 01 Jan 2000 00:00:01 +0100
Backgrounds/Aims: The serum level of hyaluronic acid (HA) has been suggested as a useful serologic marker for hepatic fibrosis. However, the relationship between serum HA levels and quantitative markers of fibrosis from liver tissue has not been reported. The aim of this study was to determine the correlation between serum HA level and quantitative measurement of hepatic fibrosis in a cirrhotic rat model. Methods: Cirrhosis was produced by common bile duct ligation (BDL) in adult Sprague-Dawley rats. The animals were classified into four groups: (1) G1, sham operated (n=5); (2) G2, BDL for 2 weeks (n=6); (3) G3, BDL for 3 weeks (n=6); and (4) G4, BDL for 4 weeks (n=6). Hepatic fibrosis was analyzed histomorphologically using the Batts and Ludwig scoring system. Serum HA level and hepatic hydroxyproline content were quantified. The gene expressions in the liver of procollagen, collagen, and transforming growth factor-β (TGF-β) were measured by reverse transcriptase-polymerase chain reaction. Results: In groups G1, G2, G3, and G4, the Batts and Ludwig scores (mean±SD) were 0, 1.3±0.5, 2.6±0.5, and 3.4±0.5, respectively (P<0.05), serum HA levels were 12.5±3.2, 30.0±4.3, 228.6±157.7, and 391.3±207.7 ng/mL (P<0.05), and the concentration of hydroxyproline was 12.4±2.8, 17.6±3.8, 17.9±2.4, and 33.4±3.4 μg/g liver tissue, and it was significantly higher in group G4 than in the other groups (P<0.05). The gene expressions of collagen, procollagen, and TGF-β1 in the liver were also significantly higher in group G4 compared with the other groups (P<0.05). Direct linear correlations were observed between serum HA level and hepatic hydroxyproline content, hepatic gene expressions of collagen, procollagen, TGF-β1, and histomorphological grade of hepatic fibrosis (P<0.001). Conclusions: These results indicate that serum HA is a useful and noninvasive serologic marker for the evaluation of advanced hepatic fibrosis. (Korean J Hepatol 2008;14:159-167)

Incidence and risk factors of acute renal failure after of acute renal failure after ...
Background/Aims: Transcatheter arterial chemoembolization (TACE) is a major modality in the treatment of unresectable hepatocellular carcinoma. Acute renal failure (ARF) may occur after TACE because of underlying liver cirrhosis and the presence of radiocontrast agent. However, the data available regarding this complication are variable and limited. The aim of this study was to determine the incidence and associated risk factors of ARF after TACE. Methods: From January 2001 to December 2004, a total of 632 procedures were performed in 377 patients. Of these, the cases with high creatinine levels (≥ 2 mg/dL) before TACE and with incomplete medical records were excluded, which resulted in 463 procedures in 319 patients (256 males and 63 females; age 58.7±9.9 years, mean±SD) being examined for this study. Various clinical and radiological data before and after the procedure were reviewed retrospectively. Results: ARF occurred following 15 (3.2%) of the 463 procedures within 7 days of TACE. Univariate analysis revealed that serum albumin levels (P=0.025), Model for End-Stage Liver Disease score (P=0.001), the distribution of Child-Pugh class (P=0.027), and the proportions of patients with ascites (P<0.001), using diuretics (P=0.010), and with a serum creatinine level ≥ 1.5 mg/dL (P=0.023) differed significantly between patients with or without ARF after TACE. In multivariate analysis, the presence of ascites (P=0.005; odds ratio, 5.297) and serum creatinine level ≥ 1.5 mg/dL (P=0.007; odds ratio, 7.358) were independently associated with the development of ARF. Conclusions: The incidence of ARF after TACE was 3.2%, and the presence of ascites and an abnormal baseline serum creatinine level were the risk factors for ARF. (Korean J Hepatol 2008;14:168-177)

Clinical feature of Fitz-Hugh-Curtis syndrome: Analysis of 25 cases

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Fitz-Hugh-Curtis syndrome is defined as perihepatitis associated with pelvic inflammatory disease (PID). We retrospectively analyzed clinical and laboratory manifestations as well as the therapeutic response in patients with clinically diagnosed Fitz-Hugh-Curtis syndrome. Methods: A cohort of 25 patients with PID and perihepatitis (as diagnosed by dynamic abdominal computed tomography (CT)) was enrolled. The prognosis, clinical manifestations, and physical examination, laboratory, and CT findings were analyzed. Results: The mean (±SD) age of the patients was 32(±8) years, and all of them were sexually active, premenopausal women, and presented with abdominal pain. Of these, 52% complained of vaginal discharge. On physical examination, right upper-quadrant tenderness was the most common finding (84%), with lower-abdominal tenderness being present in 20% of patients. On laboratory examination, erythrocyte sedimentation rate and C-reactive protein were increased in 76% and 92% of the patients, respectively. The white blood cell count was increased in 60% of them. Most patients had a normal liver function test. Using a specimen of the cervical discharge, the polymerase chain reaction to test for Chlamydia trachomatis were positive in 87% (13/15) of the patients, and Chlamydia antigen was found in 75% (9/12) of them. Dynamic abdominal CT revealed subcapsular enhancement of the liver in the arterial phase. All of the patients improved with antibiotic therapy. Conclusions: Symptoms and physical findings suggestive of PID are not present in many patients with Fitz-Hugh-Curtis syndrome. When a premenopausal woman complains of upper abdominal pain and shows CT findings compatible with perihepatitis, examination of cervical discharge would be recommended to assess the possibility of Fitz-Hugh-Curtis syndrome. (Korean J Hepatol 2008;14:178-184)

Expression of vascular endothelial growth factor (VEGF) family members and prognosis after ...
Background/Aims: Human hepatocellular carcinoma (HCC) is a hypervascular tumor, and vascular endothelial growth factor (VEGF) plays a key role in the regulation of tumor-associated angiogenesis. In this study, we analyzed the significance of the expression of VEGF family members on the prognosis and clinicopathologic progress of HCC. Methods: Surgically resected specimens of HCC and noncancerous liver tissue were obtained from 323 patients with HCC, and VEGF mRNA was examined by quantitative reverse transcriptase-polymerase chain reactions (RT-PCRs). Patients who were seropositive for hepatitis B surface antigen were selected for the analysis (n=208). The VEGF_tumor/GAPDH (glyceraldehyde-3-phosphate dehydrogenase) _tumor/VEGF_nontumor/GAPDH_nontumor ratio was calculated using a quantitative RT-PCR assay, and the relationships between the expressions of VEGF family members and clinicopathologic parameters were analyzed to evaluate their significance in the prognosis of HCC. Results: The disease-free survival was significantly worse in the high-VEGF-A group than in the low-VEGF-A group (P=0.035), whereas VEGF-A expression was not significantly related to overall survival (P=0.172). The factors significantly related to poor prognosis in univariate analysis were tumor size, portal vein invasion, microvascular thrombi, intrahepatic metastasis, tumor capsule invasion, liver capsule invasion, preoperative serum albumin level, and VEGF-A ratio. Multivariate analysis showed that a poor prognosis in HCC patients was significantly related to portal vein invasion (hazard ratio=3.381, P<0.001), intrahepatic metastasis (hazard ratio=2.379, P<0.001), tumor size (hazard ratio=1.834, P=0.003), and preoperative serum albumin level (hazard ratio=2.050, P=0.006). Conclusions: Our study showed that the expression of VEGF-A is positively correlated with the recurrence rate of HCC after curative resection. Therefore, a high expression of VEGF-A might be predictive of HCC recurrence after curative resection. (Korean J Hepatol 2008;14:185-196)

Hepatitis B core antigen expression pattern predicts response to Lamivudine therapy in patients ...
Backgrounds/Aims: Negative hepatitis B core antigen (HBcAg) staining in hepatocytes is indicative of viral replication by an active immune response. HBcAg is expressed mainly in the cytoplasm in patients with active hepatitis and hepatocyte regeneration, and mainly in the nuclei of hepatocytes in patients with minimal liver injury in the absence of hepatocyte regeneration. The aim of this study was to elucidate whether the existence and expression pattern of HBcAg predicts the response to antiviral treatment. Methods: The study involved 58 patients with biopsy-proven chronic hepatitis B who were treated with lamivudine. Hepatitis B e antigen (HBeAg), antibody to HBeAg, hepatitis B virus DNA, and alanine aminotransferase in serum were recorded every 3 months. The inflammation grade and the fibrosis stage of chronic hepatitis were scored from 0 to 4 according to lobular inflammation, portal inflammation, periportal inflammation, and fibrosis. Results: The 58 patients included 49(84%) HBcAg-positive patients, with HBcAg staining confined to the cytoplasm in 15(31%) and in both cytoplasm and nuclei in 34(69%). The grade of lobular inflammation and the total histology score were significantly higher in patients with cytoplasmic expression of HBcAg than in HBcAgnegative patients (lobular inflammation: 2.9 vs 2.1, P=0.02; total histology score: 12.2 vs 10.3, P=0.04). The virologic responses at 3, 6, 9, and 12 months differed significantly between the cytoplasmic and mixed expression groups (P<0.01). Conclusions: The expression pattern of HBcAg (including its possible absence) before initial therapy appears to predict the response to antiviral treatment. (Korean J Hepatol 2008;14:197- 205)

Four cases of toxic Liver injury associated with Dictamnus dasycarpus

Sat, 01 Jan 2000 00:00:01 +0100
We report four cases of toxic hepatitis that occurred after taking a decoction made by boiling down the root of Dictamnus dasycarpus. The four patients had a median age of 60 years, common symptoms of jaundice and general weakness, and stated that they had not consumed alcohol for at least 5 years. The markers of hepatitis A, B, and C were all negative in the patients. Abdominal ultrasonography revealed common bile ducts with normal diameters. Two of the cases were a mother and daughter, and the other two were sporadic. All of them had consumed a decoction made by boiling down the root of Dictamnus dasycarpus five or six times daily until several days before admission. Dictamnus dasycarpus induced liver injury presenting with a benign course lasting less than 1 month after cessation of the causative agent. We suggest that this natural product can cause acute hepatitis in rural areas. (Korean J Hepatol 2008;14:206-212)

Hepatitis B virus reactivation during chlorambucil and prednisolone treatment in an ...
It is generally accepted that seroconversion of hepatitis B virus (HBV) surface antigen (HBsAg) to an antibody to HBsAg (anti-HBs) indicates clearance of HBV. Here we report a case of severe hepatitis that manifested during chemotherapy in a female patient with chronic lymphocytic leukemia (CLL) who had been initially seronegative for HBsAg and seropositive for anti-HBs. The patient received chlorambucil and prednisolone for the treatment of CLL. After 6 months the serum levels of aminotransferases were increased, and HBsAg and HBV DNA were present in serum. Lamivudine was administered immediately after confirming the HBV reactivation, which considerably improved jaundice and aminotransferase levels after 3 weeks. The patient was able to resume the chemotherapy whilst continuing lamivudine treatment. This case report highlights the need for physicians to be aware of the potential risk of HBV reactivation even in an HBsAg- negative person but with detectable anti-HBc and/or anti-HBs, underscoring the need for future studies that explore the role of antiviral prophylaxis in this setting. (Korean J Hepatol 2008;14:213-218)

An adult case of glycogen storage disease type IIIa
Glycogen storage disease type III (GSD III) is a very rare disorder caused by a deficiency in the activities of glycogen debranching enzymes (amylo-1-6-glucosidase and 4-α-glucanotransferase). GSD III is characterized by the accumulation of abnormal glycogen in the liver and skeletal muscle. The primary clinical manifestations are hepatomegaly, fasting hypoglycemia, and hyperlipidemia in infants. We report a rare case of GSD III in an adult. A 52-year-old woman presented to our clinic due to dyspnea on exertion, severe general weakness, and hepatomegaly. Hypertrophic cardiomyopathy was diagnosed based on echocardiogram findings. The microscopic findings of liver and skeletal muscle biopsies were consistent with the diagnosis of GSD. DNA analysis prompted by clinical and pathologic findings led to a definitive diagnosis of GSD IIIa. Diet therapy with cornstarch was started, and the patient was followed closely. This represents the first reported case of GSD IIIa diagnosed in an adult in Korea. (Korean J Hepatol 2008;14:219-225)

Focal nodular hyperplasia-Like nodule in Liver cirrhosis

Haeryoung Kim, M.D., Ph.D., Young Nyun Park, M.D., Ph.D.1

Radiologic findings of dysplastic nodule

Joon Koo Han , Hyo Won Eun , Se Hyung Kim

The Korean Journal of Adefovir plus Lamivudine combination therapy in Lamivudine-resistant ...

So Young Kwon
Background/Aims: In lamivudine-resistant patients with chronic hepatitis B (CHB), we compared efficacy, predictive response factors and changes in viral mutants in two antiviral approaches with adefovir. Methods: A prospective cohort study on therapy with adefovir alone (29 patients) or combined with ongoing lamivudine (23 patients) was performed. Results: A virological response was achieved in 55% of patients treated with adefovir and in 83% of those treated with the combination (p>0.05). This response was directly related to the basal viral load (p<0.0001) and obtained in 10 patients with basal HBV-DNA<17,200 IU/ml using both strategies. In patients with a higher basal viral load, the virological response was more frequent when treated with the combination (p<0.05). Mutation at locus rt181 predicted HBV-DNA persistence during therapy. A virological rebound was observed in 18% of non-responders while on adefovir monotherapy. Conclusions: To achieve a complete virological response and reduce the risk of adefovir-resistant mutants in lamivudine- resistant patients, rescue therapy is preferable at early evidence of genotypic resistance. However, in subjects with a significant viral load, combination therapy is more effective. The presence of the rt181 mutation is associated with incomplete response.

2008EASL Highlights : Topics related to hepatitis B

Myoung Kuk Jang

2008EASL Highlights : Topics related to the therapy of hepatitis B

Ji Young Park

2008EASL Highlights : Topics related to hepatitis C

Seok Hyun Kim

2008EASL Highlights : Topics related to the therapy of hepatitis C

Jeong Won Jang

2008EASL Highlights : Topics related to alcoholic Liver disease

Do Young Kim

2008EASL Highlights : Topics related to nonalcoholic fatty Liver disease

Sang Hoon Park

2008EASL Highlights : Topics related to Liver cirrhosis (variceal bleeding and portal hypertension)

Yong Kyun Cho

2008EASL Highlights : Topics related to Liver cirrhosis (ascites and hepatorenal syndrome in ...

Hyung Joon Yim — Sat, 01 Jan 2000 00:00:01 +0100

2008EASL Highlights : Topics related to Liver cirrhosis (hepatic encephalopathy)

Yeon Seok Seo — Sat, 01 Jan 2000 00:00:01 +0100

2008EASL Highlights : Topics related to hepatic fibrosis

Jae Youn Cheong

2008EASL Highlights : Topics related to hepatocellular carcinoma

Sun Jung Myung

2008EASL Highlights : Topics related to the treatment of hepatocellular carcinoma

Won Young Tak

Nonalcoholic fatty Liver disease as a risk factor of cardiovascular disease

Moon Young Kim , Soon Koo Baik

Recent developments in systemic chemotherapy for hepatocellular carcinoma

Chul Ju Han
Despite recent developments in various chemotherapeutic agents and the performing of numerous clinical trials, chemotherapy still produces unsatisfactory results in hepatocellular carcinoma due to poor clinical benefit compared with untreated controls and its significant toxicity. The presence of liver cirrhosis, its complications, and decreased liver function increase the complexity of chemotherapy. There is recent evidence that targeted agents and antiangiogenic agents such as thalidomide are somewhat effective whilst having minimal toxicities. Some patients are cured by aggressive chemotherapy alone or in combination with other modalities. Therefore, if a patient is in good condition and the tumor shows some response to chemotherapy, aggressive chemotherapy might be considered. Although conventional chemotherapeutic agents are not very effective in many patients, their utility might be improved by lowering toxicities using reduced doses or by selecting only responsive patients if adequate chemosensitivity tests are available. Imaging studies have been conventional tools for evaluating tumor responses, but their results are not always reliable. Establishing criteria for accurately determining tumor responses is urgently needed, along with better chemotherapeutic drugs and regimens. (Korean J Hepatol 2008;14:4-11)

Nonalcoholic steatohepatitis: Pathogenesis and treatment

Sang Hoon Park
Nonalcoholic fatty liver disease (NAFLD) is characterized by a wide spectrum of liver damage spanning steatosis, nonalcoholic steatohepatitis (NASH), cryptogenic liver cirrhosis, and even to hepatocellular carcinoma. Investigations in the last few years have focused on NASH, a relatively aggressive form of liver disease, due largely to the explosion of information provided by clinical and basic science studies related to the widespread presence of risk factors, such as obesity, type II diabetes mellitus, and dyslipidemia. This is especially important given that obesity and type II diabetes mellitus have recently reached epidemic proportions in Korea. The pathogenesis of NASH is multifactorial, with insulin resistance and increased fatty acid possibly being important factors in the accumulation of hepatocellular fat, and oxidant stress, lipid peroxidation, mitochondrial dysfunction, and dysregulation of variable cytokines possibly being important causes of hepatocellular injury in steatotic liver. Because not all steatotic livers progress to NASH, some other environmental factors or a combination of genetic factors are thought to be required for progression to NASH and fibrosis. Lifestyle modifications continue to be the cornerstone therapy in NAFLD, but some insulin-sensitizing drugs might be more effective in treating NASH. Many pilot trials for antioxidants and lipid-lowering and hepatic protective agents have yielded promising initial results in improving liver enzymes or features of liver histology. However, the efficacy of these agents remains questionable. Despite recent gains in understanding NASH, several issues related to its natural history, pathogenesis, and treatment remain unresolved. (Korean J Hepatol 2008;14:12- 27)

Distribution of hepatitis C virus genotypes in Jeju Island

Sat, 01 Jan 2000 00:00:01 +0100
Backgrounds/Aims: The hepatitis C virus (HCV) genotype affects clinical outcomes of HCV infection, in terms of the response to antiviral therapy and progression of chronic liver diseases, and shows geographic differences in distribution. The aim of this study was to elucidate the HCV genotypes in patients with chronic HCV infection in Jeju, which is an island off the Korean peninsula. Methods: The study population consisted of 162 patients with anti-HCV antibodies and HCV-RNA. HCV genotypes were determined using genotype specific primers. Results: HCV genotype 2a predominated (62.3%), followed by genotype 1b (34.0%) and 2b (3.7%). The prevalence of genotypes differed significantly with age, with HCV genotypes 1 and 2 being more frequent in older and younger subjects (P=0.035), respectively. HCV-RNA levels were higher in patients with genotype 1 than in those with genotype 2 (P=0.001). HCV genotype was not significantly related to sex, clinical diagnosis and potential risk factors. Conclusions: HCV genotype 2a is most common in Jeju, followed by genotype 1b. Our results suggest that the distribution of the HCV genotype differs between regions in Korea. (Korean J Hepatol 2008;14:28-35)

Clinical outcome of pegylated interferon and ribavirin therapy for chronic hepatitis C

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: The purpose of this study is to elucidate the efficacy and safety of combined peginterferon and ribavirin therapy in Korean patients with chronic HCV infection. Methods: We retrospectively analyzed the clinical records of 84 patients. Thirty five patients with genotype 1 HCV infection were treated with peginterferon α-2a 180 μg/week and ribavirin 1,000-1,200 mg/day for 48 weeks, and 49 patients with genotype non-1 were treated with peginterferon α-2a 180 μg/week and ribavirin 800 mg/day for 24 weeks. Results: An early virologic response was seen in 87.0% of patients with genotype 1 HCV. An end of treatment response (ETR) was seen in 82.6% and 97.6% of patients with genotype 1 and genotype non-1, respectively. An overall sustained virologic response (SVR) was seen in 53 patients (82.8%) of the 64 patients: in 16 (69.6%) of 23 patients with genotype 1 and in 37 (90.2%) of 41 patients with genotype non-1. An end of treatment biochemical response was seen in 58 patients (90.6%) [genotype 1, 20 patients (87.0%); genotype non-1, 38 patients (92.7%)], and a sustained biochemical response was achieved in 49 patients (76.6%) [genotype 1, 14 patients (60.9%); genotype non-1, 35 patients (85.4%)]. Independent factors affecting an SVR were HCV genotype and the baseline HCV RNA level. Conclusions: This study shows that a combination therapy of peginterferon and ribavirin is highly effective for chronic HCV infection, producing a high SVR and ETR. (Korean J Hepatol 2008;14:36-45)

Comparison of therapeutic results between combination therapy of peginterferon alpha-2a plus ...

Heon Ju Lee , Jong Ryul Eun , Jae Won Choi , Kyung Ok Kim , Hee Jung Moon — Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: This study compared the efficacy and safety of combined peginterferon alfa (PEG-IFN) and ribavirin with that of combined interferon alpha (IFN-α) and ribavirin, according to the treatment duration in Korean patients with chronic hepatitis C. Methods: Medical records of 86 patients treated with PEG-IFN and ribavirin (mean age, 50.7 years; males/females, 57/29; genotypes 1/2, 59/27) and 134 patients treated with IFN-α and ribavirin (mean age, 50.9 years; males/females 74/60; genotypes 1/2, 79/55) were reviewed. Ribavirin was administered at doses of 600-1,200 mg and 600-800 mg in patients with genotypes 1 and 2, respectively. Results: Sustained virological responses (SVRs) were evident in 68.4% and 41.7% of genotype 1 patients treated for 48 weeks in the PEG-IFN and IFN-α groups, respectively (P=0.021), and in 94.1% and 64.9% of genotype 2 patients treated for 24 weeks (P=0.026). Some genotype 1 patients treated for 24 weeks in the PEG-IFN group, who all exhibited negative HCV PCR results at week 12, showed an SVR of 87.5% (7/8). Conclusions: The rate of SVRs in Korean patients with chronic hepatitis C was higher for combined PEG-IFN and ribavirin than for combined IFN-α and ribavirin. Further study is needed to clarify the outcome of short-term therapy in patients with a rapid or early virological response. (Korean J Hepatol 2008;14:46- 57)

Factors affecting initial virologic response and emergence of resistant mutants after adefovir ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients. Methods: This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction- fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants. Results: After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01). Conclusions: Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant. (Korean J Hepatol 2008;14:58-66)

The significance of anti-HBc and occult hepatitis B virus infection in the occurrence of ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Alcohol and the hepatitis B virus (HBV) exert synergistic effects in hepatocelluar carcinogenesis. We aimed to elucidate the clinical significance of the antibody to hepatitis B core antigen (anti-HBc) and occult HBV infection on the development of hepatocellular carcinoma (HCC) in patients with alcoholic liver cirrhosis (LC). Methods: Patients with alcoholic LC alone (n=193) or combined with HCC (n=36), who did not have HBsAg or antibody to hepatitis C virus were enrolled. Clinical data and laboratory data including anti-HBc were investigated at enrollment. The polymerase chain reaction was applied to HBV DNA using sera of patients with HCC or LC after age and sex matching. Results: Patients with HCC were older (60±11 years vs. 53±10 years, mean±SD, P<0.001), more likely to be male (100% vs. 89%, P=0.03), and had a higher positive rate of anti-HBc (91.2% vs. 77.3%, P=0.067), and a higher alcohol intake (739±448 kg vs. 603±409 kg, P=0.076) than those with LC. Age was the only significant risk factor for HCC revealed by multiple logistic regression analysis (odds ratio, 1.056; P=0.003). The positive rate of anti-HBc and alcohol intake did not differ in age- and sex-matched subjects between the LC (n=32) and HCC (n=31) groups. However, the detection rate of serum HBV DNA was higher in the HCC group (48.4%) than in the LC group (0%, P<0.001). Conclusions: Anti-HBc positivity is not a risk factor for HCC. However, occult HBV infection may be a risk factor for HCC in patients with alcoholic LC. (Korean J Hepatol 2008;14:67-76)

Nonalcoholic fatty Liver disease as a risk factor of cardiovascular disease; Relation of ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with abdominal obesity, dyslipidemia, hypertension, and Type 2 diabetes, which are all features of the metabolic syndrome. The aim of the present study was to elucidate whether NAFLD is associated with carotid atherosclerosis. Methods: The study population comprised 659 subjects without hepatitis B and C infections and who did not consume alcohol. Fatty infiltrations of liver were detected by abdominal ultrasonography, and intima-media thickness (IMT) and plaque prevalence were estimated by carotid ultrasonography. Results: The mean values of systolic and diastolic pressures, body mass index (BMI), aspartate aminotransferase, alanine aminotransferase, gamma- glutamyl transpeptidase, uric acid, total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, fasting glucose, fasting insulin, homeostasis model of assessment (HOMA) index, hemoglobin A1c, and plasminogen activator inhibitor-1 differed significantly between patients with NAFLD (n=314) and normal controls (n=345). The carotid IMT was 0.817±0.212 (mean±SD) mm in patients with NAFLD and 0.757±0.198 mm in normal controls (p<0.001). The prevalence of carotid plaques was higher in patients with NAFLD (26.4%) than in normal controls (15.9%) (p<0.001). This association persisted significantly after adjusting for age, sex, BMI, HOMA index and individual factors of metabolic syndrome by multiple logistic regression analysis. Conclusions: Patients with NAFLD are at a high risk of carotid atherosclerosis regardless of metabolic syndrome and classical cardiovascular risk factors. Therefore, the detection of NAFLD should alert to the existence of an increased cardiovascular risk. Moreover, NAFLD might be an independent risk factor for cardiovascular disease. (Korean J Hepatol 2008;14:77-88)

Hepatic myelopathy as a presenting neurological complication in patients with cirrhosis and ...

Sat, 01 Jan 2000 00:00:01 +0100
Hepatic myelopathy is a rare complication of chronic liver disease that is associated with extensive portosystemic shunts. The main clinical feature of hepatic myelopathy is progressive spastic paraparesis in the absence of sensory or sphincter impainn1ent. Early and accurate diagnosis of hepatic myelopathy is important because patients with early stages of the disease can fully recover following liver transplantation. Motor-evoked potential studies may be suitable for the early diagnosis of hepatic myelopathy, even in patients with preclinical stages of the disease. Here we describe two patients who presented with spastic paraparesis associated with a spontaneous splenorenal shunt and without any previous episode of hepatic encephalopathy. One patient experienced improved neurologic symptoms after liver transplantation, whereas the other patient only received medical treatment, which did not prevent the progression of spastic paraparesis. (Korean J Hepatol 2008;14:89-96)

A case of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis

Sat, 01 Jan 2000 00:00:01 +0100
Allopurinol-induced hypersensitivity syndrome is characterized by an idiosyncratic reaction involving multiple-organs, which usually begins 2 to 6 weeks after starting allopurinol. In rare cases, the adverse reactions to allopurinol are accompanied by a variety of liver injury, such as reactive hepatitis, granulomatous hepatitis, vanishing bile duct syndrome, or fulminant hepatic failure. Here we report a case with granulomatous hepatitis and ductopenia. A 69-year-old man with chronic renal failure, hyperuricemia, and previously normal liver function presented with jaundice, skin rash, and fever 2 weeks after taking allopurinol (200 mg/day). In histopathology, a liver biopsy specimen showed mild spotty necrosis of hepatocytes, marked cholestasis in parenchyma, and some granulomas in the portal area. There were vacuolar degeneration in the interlobular bile ducts and ductopenia in the portal tracts. Pathologic criteria strongly suggested the presence of allopurinol-induced granulomatous hepatitis with ductopenia and cholestasis. The patient fully recovered following the early administration of systemic corticosteroid therapy. (Korean J Hepatol 2008;14:97-101)

A case of ticlopidine induced acute cholestatic hepatitis and pure red cell aplasia

Sat, 01 Jan 2000 00:00:01 +0100
Ticlopidine inhibits platelet aggregation and provides beneficial secondary prevention of cerebrovascular and coronary artery disease. Frequently reported adverse effects of ticlopidine include diarrhea, nausea, and rash. However, to our knowledge, there are only a few published reports of the simultaneous occurrence of cholestatic hepatitis and pure red cell aplasia. Here we report a patient with simultaneous severe cholestatic hepatitis and pure red cell aplasia associated with ticlopidine. Although these adverse effects are rare, periodic hematological and liver function tests are recommended after starting ticlopidine. (Korean J Hepatol 2008; 14:102-107)

Hepatic adenomatosis in glycogen storage disease

Ji Eun Kwon , Young Nyun Park — Sat, 01 Jan 2000 00:00:01 +0100

Angiomyolipoma

Won Jae Lee — Sat, 01 Jan 2000 00:00:01 +0100

The Korean Journal of Normal range of serum ALT level in patients with chronic hepatitis

Yeon Seok Seo
The clinical significance of persistently normal ALT in chronic hepatitis B infection Lai M, Hyatt BJ, Nasser I, Curry M, Afdhal NH Background/Aims: Chronic hepatitis B virus (HBV) disease is caused by both necroinflammation and active viral replication. The role of ALT levels as a predictor of liver injury has recently been questioned. The aim of the study was to determine whether normal ALT is associated with liver injury in a cohort of HBV patients undergoing liver biopsy. Methods: This is a retrospective review of chronic HBV patients divided into 3 groups; (1) persistently normal ALT (PNALT); (2) ALT 1~1.5× ULN and (3) ALT > 1.5× ULN. Multiple clinical, biochemical, virological variables were evaluated. Results: One hundred and ninety-two patients met the inclusion criteria, 59 with PNALT, 26 with ALT 1~1.5× ULN, and 107 with ALT > 1.5× ULN. Increasing age, higher ALT, higher grade of inflammation on biopsy, and HBeAg positivity predicted fibrosis. 18% of patients with PNALT had stage 2+ fibrosis and 34% had grade 2 or 3 inflammation. Overall 37% of patients with PNALT had significant fibrosis or inflammation. Subgroup analysis showed the majority with fibrosis belonged to the high normal ALT group and that only a minority who were young and immune tolerant had significant findings on biopsy. Conclusions: There is significant fibrosis and inflammation in 37% of patients with PNALT and a liver biopsy should be considered in patients older than 40 with high normal ALT. [J Hepatol 2007;47:760-767

KASL Guidelines : Management of Chronic Hepatitis B

Sat, 01 Jan 2000 00:00:01 +0100

Review: Clinical Outcome after Living Donor Liver Transplantation in Patients with Hepatitis C ...

Hyung Joon Kim — Thu, 01 Jan 1970 09:00:00 +0100

Recent Etiology and Clinical Features of Acute Viral Hepatitis in a Single Center of Korea
Background/Aims: The etiology of acute viral hepatitis in Korea has been dynamically changing during the recent years. The aim of this study was to investigate the recent etiology and the clinical features of acute viral hepatitis in a single center of Korea. Methods: We performed a retrospective analysis of a prospective cohort of 55 patients who were diagnosed with acute viral hepatitis A to E during the period from May 2005 to August 2006. In addition to the clinically acute manifestations, the confirmatory serological tests were performed for the diagnosis of acute hepatitis A, B, C and E. Results: The proportion of patients with acute viral hepatitis A, B, C, E and others were 56.4% (n=31), 12.7% (n=7), 18.2% (n=10), 9.1% (n=5) and 3.6% (n=2), respectively. The mean age of the patients with acute hepatitis A, B, C and E were 29.1±4.38, 38.7±11.72, 45.3±17.62 and 32.4±6.58 years, respectively. There was no fatal case. All cases of acute hepatitis B and six out of ten cases of acute hepatitis C recovered spontaneously. Four out of the five patients with acute hepatitis E had no history of travel to endemic area. Conclusions: The most common etiology of acute viral hepatitis in Korea is hepatitis A virus, and hepatitis C and B virus were the next most common causes. The sporadic cases of acute hepatitis E were not rare, and coinfection of HAV and HEV was observed. A multicenter, prospective study is warranted in the future. (Korean J Hepatol 2007;13:495-502)

The Efficacy and Safety of Telbivudine in Korean Patients with Chronic Hepatitis B
Background/Aims: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus. Methods: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment. Results: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine. Conclusions: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine. (Korean J Hepatol 2007;13:503-512)

Change of HBV DNA Level as a Predictor of HBeAg Loss after Lamivudine Treatment
Backgroud/Aims: Lamivudine is an effective, safe therapeutic agent for the treatment of chronic hepatitis B. The aim of this study was to investigate whether early suppression of the viral load predicts HBeAg loss within 1 year during lamivudine therapy. Methods: This prospective study encompassed 74 patients (mean age: 37.1 years, male/female: 51/23) who were positive HBeAg, their AST or ALT levels were ≥2 times the upper limit of normal and their HBV DNA was ≥105 copies/mL. The patients received lamivudine 100 mg for 12 months with monitoring their HBV DNA, AST, ALT, HBeAg and anti-HBe, and all these tests were performed at pretreatment and 1, 3, 6, 9 and 12 months after treatment. The serum HBV DNA was measured by HBV branched DNA assay. Results: HBeAg loss was observed in 12 patients (16.2%), and 9 patients achieved anti-HBe seroconversion during up to 1 year of lamivudine therapy. The mean time to HBeAg loss was 5.6 months (range: 1-12 months). The posttreatment HBV DNA (<2,000 copies/mL) after 3 month (P=0.008) and 6 month (P=0.012)) were significant predictors of HBeAg loss after 1 year of lamivudine treatment on univariate analysis. Pretreatment HBV DNA, AST/ALT, gender, age and liver cirrhosis had no impact on HBeAg loss. The six-month posttreatment HBV DNA level <2,000 copies/mL was a significant predictor of HBeAg loss on multivariate analysis (P=0.008, odds ratio=0.108). Conclusion: We suggest that an HBV DNA level <2,000 copies/mL at 6 month after lamivudine therapy is the most important predictor of HBeAg loss during up to 1 year of lamivudine therapy. (Korean J Hepatol 2007;13:513-520)

Liver Stiffness Measurement for the Diagnosis of Hepatic Fibrosis in Patients with Chronic ...
Background/Aims: FibroScanⓇ is a new medical device that noninvasively measures liver stiffness. The aim of this study was to assess the accuracy of the liver stiffness measurement by FibroScanⓇ for making the diagnosis of liver fibrosis in patients with chronic viral hepatitis. Methods: We studied 103 patients with chronic viral hepatitis B or C and they underwent FibroScanⓇ and liver biopsy between October 2005 and August 2006. Liver fibrosis was staged on a 0-4 scale according to the Korean Society of Pathologists Scoring System. The diagnostic accuracy was assessed by analysis of the receiver operator characteristics (ROC). Results: The liver stiffness was 3.5-57.1 kPa (mean: 11.8, SD: 8.9). The mean value of liver stiffness in each fibrosis stage group (F1, F2, F3 and F4) was 5.8±1.8 kPa, 11.3±6.8 kPa, 11.8±6.0 kPa and 23.4±16.5 kPa, respectively. Liver stiffness measured by FibroScanⓇ showed reliable correlation with the liver fibrosis stage as confirmed by liver biopsy (r=0.56, p<0.001). The AUROC (95% CI) of ≥ F2, ≥ F3 and F4 was 0.93 (0.86-0.99), 0.72 (0.62-0.82) and 0.80 (0.67-0.92), respectively. The sensitivity and specificity of 7.5 kPa, which was the cutoff value for ≥ F2, was 84% and 90%, respectively. Conclusions: FibroScanⓇ is a reliable method for the diagnosis of significant fibrosis (≥ F2) and cirrhosis in patients with chronic liver disease. The liver stiffness measurement by FibroScanⓇ showed good diagnostic performance for significant fibrosis. (Korean J Hepatol 2007;13:521-529)

Five-year Survival Analysis of a Cohort of Hepatocellular Carcinoma Patients Who Treated at the ...
Background/Aims: We investigated the five-year survival outcomes of a large cohort of hepatocellular carcinoma (HCC) patients who were treated at a single institute, and this is a follow-up study of a previous report. Methods: Nine hundred four HCC patients who were treated at the National Cancer Center Korea were enrolled and they were followed till February 2007. Results: The mean age of the patients was 56.0 years and 731 patients were male. Six hundred seventy-seven (74.9%) patients died and the overall 5-year survival rate (5-YSR) was 23.9%. The 5-YSRs of the patients with modified UICC stage I, II and III were 61.2%, 54.4% and 18.4%, respectively, and the median survival time was 4.3 and 3.7 months for the stage IVa and IVb patients, respectively. For the analysis of the treatment modality, surgical resection showed significantly better outcomes for the five-year survival as compared with transcatheter arterial chemoembolization (TACE) for Child-Pugh A patients with modified UICC stage I or II disease (80.1% vs 52.8%, respectively, P<.001), or stage III disease (60.7% vs 17.0%, respectively, P<.001). For patients with advanced stage IVb disease, TACE, systemic chemotherapy and radiotherapy increased the median survival period more than conservative management for the Child-Pugh class A patients. The serum alpha-fetoprotein level, portal vein tumor thrombosis, the Child-Pugh class, the tumor stage, the tumor type and symptoms were related to the prognosis. Conclusions: This study presented, for the first time, the 5-YSRs of a cohort of HCC patients. (Korean J Hepatol 2007;13:530-542)

Clinical Outcome after Living Donor Liver Transplantation in Patients with Hepatitis C ...
Background/Aims: Hepatitis C virus (HCV)-associated cirrhosis is an increasingly frequent indication for liver transplantation (LT). However, HCV recurrence is universal and this immediately occurs following LT, which endangers both the graft and patient survival. We investigated the frequency of posttransplant recurrence of HCV infection and the patient-graft survival, and we analyzed the responses to ribavirin and interferon therapy in the patients with recurrent HCV infection after living donor liver transplantation (LDLT). Methods: We retrospectively reviewed the clinical outcomes of 39 HCV-associated cirrhosis patients who underwent LDLT at Asan Medical Center between August 1992 and June 2006. In this study, the diagnosis of recurrent HCV was made on the basis of increased transaminases and serum HCV RNA levels greater than 10 million IU/mL because protocol liver biopsy was not performed. Results: HCV recurrence was seen in 26 of the 39 LDLT patients (66.7%). 86.7% of recurrence occurred within the first postoperative year. Antiviral treatment was used for all patients with recurrence of HCV. None of the 10 patients receiving ribavirin alone and 9 of 16 patients who received combination therapy with pegylated interferon alpha-2a plus ribavirin became HCV RNA negative and they remained persistently negative during the median follow-up of 24.9 months. Our data indicates that there is no significant factor influencing HCV recurrence except for the recipient`s age. The 2-year patient survival for the HCV patients with HCC and those patients without HCC were 81.2% and 81.3%, respectively (P=0.85) and the 2-year graft survival rates were 81.2% and 68.2%, respectively (P=0.29). No patient died from HCV recurrence during the follow-up period. Conclusions: Combination therapy with ribavirin and interferon appears to improve the outcome of recurrent HCV infected patients after LDLT. (Korean J Hepatol 2007;13:543-555)

A Case of Imported Dengue Fever with Acute Hepatitis
Dengue fever is an acute febrile disease caused by the dengue virus, which belongs to the flaviviridae family, and this virus is transmitted by the bite of the mosquito Aedes aegypti. It occurs in the tropical climates of the South Pacific, Southeast Asia, India, Africa and the subtropical zone of America. Imported cases of Dengue fever and Dengue hemorrhagic fever are rapidly increasing as many Koreans are now traveling abroad. Liver injury is usually detected by laboratory investigation according to a surveillance protocol. Although liver injury by dengue virus has been described in Asia and the Pacific islands, the pathogenic mechanisms are not yet fully clarified. It is usually expressed in a self-limiting pattern and the patient has a complete recovery. We report here on a case of a young woman who presented with general weakness, nausea and significant elevation of the aminotransferase levels, and she was diagnosed with dengue fever. (Korean J Hepatol 2007;13:556-559)

A Case of Solitary Fibrous Tumor of the Liver
A 46-year-old woman was found to have a huge liver mass that was detected by abdominal ultrasonography. Abdominal CT and MRI showed a 10 cm-sized, encapsulated mass occupying the anterior segment of the right hepatic lobe. Extended right hemihepatectomy was performed and pathological examination revealed fibroblast-like spindle cells within dense deposits of collagen. On immunohistochemical staining, these spindle tumor cells showed an intense CD34 immunoreactivity. The patient is alive without evidence of tumor recurrence 7 months after the resection. Solitary fibrous tumor is a very rare neoplasm found in the liver parenchyma, and it has been reported in less than 30 patients in the English literature. We present here the first such case in Korea. (Korean J Hepatol 2007;13:560-564)

A Case of Fulminant Hepatic Failure Secondary to Hepatic Metastasis of Small Cell Lung Carcinoma
Although liver metastasis is commonly found in cancer patients, fulminant hepatic failure secondary to diffuse cancer infiltration into the liver is rare. Liver metastasis-induced fulminant hepatic failure has been reported in patients with primary cancer of the gastrointestinal tract, breast and uroepithelium, and in patients with melanoma and hematologic malignancy. Small cell lung cancer is so highly invasive that hepatic metastasis is common, but rapid progression to fulminant hepatic failure is extremely rare. We report here on a case of a patient who died because of rapid progression to fulminant hepatic failure as a result of hepatic metastasis of small cell lung carcinoma. (Korean J Hepatol 2007;13:565-570)

Combined Hepatocellular-cholangiocarcinoma

Yoon Mi Jeen , So Young Jin

The Korean Journal of The Efficacy of Sorafenib for Patients With Advanced Hepatocellular Carcinoma

Jeong Heo

2007 AASLD Topics : Topics Related to Hepatitis B

Ji Young Park — Sat, 01 Jan 2000 00:00:01 +0100

2007 AASLD Topics : Topics Related to Therapy of Hepatitis B

Ji Hoon Kim

2007 AASLD Topics : Topics Related to Hepatitis C

Hyn Young Woo

2007 AASLD Topics : Topics Related to Therapy of Hepatitis C

Jong Ryul Eun

2007 AASLD Topics : Topics Related to Non-alcoholic Fatty Liver Disease

Dong Hee Kim

2007 AASLD Topics : Topics Related to Alcoholic Liver Disease

Hyun Deok Shin

2007 AASLD Topics : Topics Related to Autoimmune Liver Diseases

So Young Jin

2007 AASLD Topics : Topics Related to Liver Cirrhosis

Jong In Yang

2007 AASLD Topics : Topics Related to Hepatocellular Carcinoma

Woo Young Shin

2007 AASLD Topics : Topics Related to Liver Transplantation

Koo Jeong Kang

Treatment of Chronic Hepatitis C: Shorter Treatment Duration For Genotype 2 or 3 Infection

Sook Hyang Jeong

Microbiological Characteristics of Spontaneous Bacterial Peritonitis in Korea

Jeong Heo, M.D., Soon Ho Um, M.D.1

The Role of Activated Hepatic Stellate Cells in Liver Fibrosis, Portal Hypertension and Cancer ...

June Sung Lee , Jong Hoon Kim
Although hepatic stellate cells, which are liver specific pericytes, have been recognized within the vasculature of the sinusoid for more than one hundred years, the biology and function of these cells is unclear. Recent studies have highlighted the key role of stellate cells in a number of fundamental processes that include wound healing/fibrosis, vasoregulation, and vascular remodeling/angiogenesis. In the liver, these processes are particularly important in the development of cirrhosis, portal hypertension and cancer. This article highlights the recent advances in our understanding of the biology of hepatic stellate cells and discusses some of the recently-ascribed functions that are relevant to liver fibrosis, portal hypertension and cancer angiogenesis. (Korean J Hepatol 2007;13:309-319)

Molecular Mechanisms of Hepatitis B Virus-associated Hepatocellular Carcinoma

Neung Hwa Park, M.D., Young-Hwa Chung, M.D.1
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. The hepatitis B virus (HBV) replicates non-cytopathically in hepatocytes, and most of the liver injury associated with this infection reflects the immune response. Epidemiological studies have clearly demonstrated that a chronic HBV infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes during the malignant transformation have been identified. The main carcinogenic mechanism of HBV-associated HCC is related to the long term-inflammatory changes caused by a chronic hepatitis B infection, which might involve the integration of the HBV. Integration of the HBV DNA into the host genome occurs at the early steps of clonal tumorous expansion. The hepatitis B x protein (HBx) is a multifunctional regulatory protein that communicates directly or indirectly with a variety of host targets, and mediates many opposing cellular functions, including its function in cell cycle regulation, transcriptional regulation, signaling, encoding of the cytoskeleton and cell adhesion molecules, as well as oncogenes and tumor suppressor genes. Continued study of the mechanisms of hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformations in the liver. This review summarizes the current knowledge of the mechanisms involved in HBV-associated hepatocarcinogenesis. (Korean J Hepatol 2007;13:320-340)

Short-term Therapy with Pegylated Interferon plus Ribavirin for the Chronic Hepatitis C ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: The standard treatment for chronic hepatitis C patients infected with HCV genotype-2 is a combination of pegylated interferon alfa and ribavirin over a 24 week period. It is unclear if a shorter treatment duration is possible for patients showing a rapid virological response (RVR) without compromising the sustained virologic response (SVR) in Korea. Methods: 42 patients chronically infected with the HCV genotype-2 were treated with peginterferon alfa-2a 180 mcg/wk plus ribavirin 800 mg/d for 24 weeks and followed up for 24 weeks. The HCV RNA was qualitatively assessed after 4 weeks of treatment, and RVR was defined as undetectable HCV RNA at the 4th week. Retrospectively, 26 patients were treated with the standard treatment strategy (≥80% of the intended duration and dosage), 14 patients with a short-term treatment strategy (<80% intended duration and dosage) and 2 patients were excluded. Results: Among the 42 patients, 35 patients (83%) had RVR and 38 patients (90%) had a sustained virologic response (SVR). All 7 patients without RVR were treated with the standard treatment strategy, in whom 6 patients (86%) had SVR. Among the 35 patients with RVR, 14 patients were treated with short-term treatment and 19 patients were treated with the standard treatment. SVR was obtained in 12 out of the 14 patients (86%) in the short-term treatment group and 18 out of the 19 (95%) in the standard treatment group (P=0.373). Conclusion: HCV genotype-2 patients who have RVR with peginterferon and ribavirin treatment can be treated with a short-term treatment without compromising the chances for SVR. However, an additional trial will be needed to optimize the treatment duration. (Korean J Hepatol 2007;13:341-348)

Effect of Initial Virologic Response to Adefovir on the Development of Resistance to Adefovir ...
Background/Aims: Adefovir dipivoxil (ADV) resistance in patients with lamivudine-resistant chronic hepatitis B is not well understood. This study examined the initial virologic response (IVR) to ADV, the rate of ADV resistance and the factors associated with ADV resistance. Methods: Eighty one lamivudine-resistant HBeAg-positive patients were enrolled in this study. IVR was defined as HBV DNA < 4 log10 copies/mL after 6 months of therapy. Results: IVR was observed in 37/81(45.7%) patients and it was associated with higher pretreatment ALT (P=0.002), and low pretreatment HBV DNA level (P=0.015). The HBV DNA levels were significantly higher in the non-IVR patients than the IVR patients at 12, 18 and 24 months (4.73 vs 2.59, 4.53 vs 2.31, 4.39 vs 2.40 log10 copies/mL, respectively; P<0.01). During the follow-up period, 17(21.0%) patients showed phenotypic resistance to ADV and 9 (11.1%) patients had ADV-resistant mutations. The cumulative probabilities of the phenotypic resistance to ADV at 12 and 24 months were 8.7% and 32.5%, respectively. The cumulative probabilities of the genotypic resistance to ADV at 12 and 24 months were 0% and 14.6%, respectively. Resistance to ADV was associated with a higher pretreatment HBV DNA (P=0.019), and non-IVR (P<0.001). Conclusions: The cumulative probabilities of the phenotypic and genotypic resistance to ADV at 24 months were 32.5% and 14.6%. The high pretreatment HBV DNA and non-IVR (HBV DNA ≥ 4 log10 copies/mL after 6 months of therapy) were associated with ADV resistance. (Korean J Hepatol 2007;13: 349-362)

Comparison of Recent IgG Anti-HAV Prevalence between Two Hospitals in Seoul and Gyeonggi area
Background/Aims: Recently, the incidence of acute hepatitis A has increased nationwide and is related to the low rate of IgG anti-HAV. This study compared the prevalence of IgG anti-HAV in two university hospitals located in a large city and in a small city including a rural region according to age, gender, and the year of diagnosis. Methods: IgG anti-HAV was measured in a total of 4299 patients, who visited Seoul or Guri Hanyang University Hospital between January 2002 and December 2006. Results: The positive rates of the antibody in Seoul and Guri hospitals were 52.7% vs 57.1% in under the age of 1, 40.7% vs 42.2% in age of 1 to 4, 31.8% vs 30.3% in age of 5 to 9, 24.8% vs 27.1% in age of 10 to 14, 11.6% vs 18.2% in age of 15 to 19, 23.0% vs 20.3% in age of 20 to 24, 40.5% vs 42.9% in age of 25 to 29, 67.5% vs 75.0% in age of 30 to 34, 86.5% vs 88.1% in age of 35 to 39, 95.3% vs 93.6% in age of 40 to 44, 97.0% vs 98.7% in age of 45 to 49, and 98.5% vs 98.6% in patients who were more than 50, respectively. The positive rates of the antibody were not significantly different between two sites according to each age group and gender. Conclusions: The results confirmed the low rates of IgG anti-HAV, particularly in the ages of 10-24 that match the age group of recently increased incidence of acute hepatitis A nationwide. Therefore, measurement of the antibody and vaccination should be considered in this age group. (Korean J Hepatol 2007;13:363-369)

Changes in the Profiles of Causative Agents and Antibiotic Resistance Rate for Spontaneous ...
Backgrounds/Aims: The causative agents for spontaneous bacterial peritonitis (SBP) and antibiotic resistance rate vary according to the regions and time. This study evaluated the recent changes in the profiles of microorganisms and antibiotic resistance rate for the choice of effective antibiotics in treating SBP. Methods: The clinical records of 1,018 episodes of SBP from November, 1994 to December, 2005, were analyzed retrospectively. The profiles of the causative agents for SBP and the rate of antibiotic resistance were compared in every 4-year-term. Results: The microorganisms were isolated in 394 out of 1018 episodes (38.7%). Gram negative and positive organisms constituted 71.6% and 21.3%, respectively. The five most commonly isolated organisms were E. coli (35.8%), K. pneumoniae (15.5%), viridans Streptococci (10.4%), S. pneumoniae (4.8%) and Aeromonas group (4.6%). The rate of E. coli resistant to cefotaxime (0%, 5.4%, 7.4%) and ciprofloxacin (4.3%, 21.6%, 28.4%) were increased in recent years. In the gram positive organisms, all isolates of viridans Streptococci and Pneumococci were sensitive to cefotaxime and ciprofloxacin. Recently, methicillin-resistant Staphylococcus aureus (MRSA) (28%) and vancomycin-resistant Enterococci (VRE) (31%) have been isolated. In each period, the overall antibiotic resistance rates to cefotaxime were 12.5%, 14.0%, 14.8%, to ciprofloxacin were 3.1%, 16.7%, 18.0%, and to imipenem were 4.7%, 7.0%, 4.2%. Conclusions: Cefotaxime may still be the choice of primary empirical antibiotics for the treatment of SBP in Korea because the rate of resistance is acceptable. However, it is important to be aware of the recent increase in ciprofloxacin-resistant E. coli, extended spectrum beta-lactamase (ESBL)-producing gram negative bacilli, MRSA and VRE. (Korean J Hepatol 2007;13:370-377)

Efficacy of Transarterial Chemolipiodolization with or without 3-Dimensional Conformal ...
Background/Aims: The treatment efficacy for advanced hepatocellular carcinoma is poor. This study examined the efficacy and toxicity of 3-dimensional conformal radiotherapy (3D-CRT) in combination with transarterial chemolipiodolization (TACL) for a huge hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: From March 2001 to November 2004, 49 patients with advanced HCC with PVTT (size>8 cm, modified UICC stage IVa) were enrolled in this retrospective study. Twenty two patients underwent more than 2 cycles of TACL (adriamycin 50 mg/m2, cisplatin 60 mg/m2, 5-fluorouracil 200 mg/m2 every 4-6 weeks) without 3D-CRT, while 27 patients underwent consecutive TACL with 3D-CRT (40-45 Gy for 4-5 weeks) that was started one week after the 1st TACL. The response was assessed by a computed tomography (CT) and the serum alpha-fetoprotein (AFP) level at 1-2 month intervals. Results: The objective response rates in the TACL group and TACL with 3D-CRT group were 18% and 48% at 3 months (P=0.051), and 10.5% and 42% at 6 months (P=0.024) respectively. The median survival time was 13 months and 13.5 months in TACL and TACL with 3D-CRT groups, respectively (P=0.502). The treatment response was better in the TACL with 3D-CRT group but there was no significant difference in survival between the two groups. Most toxicities in the two groups were mild, not exceeding grade 1 according to the WHO criteria. Conclusions: For patients with a huge HCC with PVTT, TACL with 3D-CRT achieved some meaningful clinical benefit. Prospective controlled trials will be needed to confirm the real benefit of TACL combined with 3D-CRT. (Korean J Hepatol 2007;13:378-386)

Clinical Features and Treatment Outcome of Advanced Hepatocellular Carcinoma with Inferior vena ...
Background/Aims: Hepatocellular carcinoma (HCC) with an extension to the inferior vena cava (IVC) or right atrium is uncommon, and its prognosis remains unclear due to the few case reports. In order to elucidate the natural history and treatment outcome, this study investigated advanced HCC patients with an IVC invasion or atrial tumor thrombus. Methods: Between November 1987 and June 2004, a total of 41 patients were diagnosed as having HCC with IVC or right atrial involvement using the new imaging techniques including a two-dimensional echocardiography. Those patients were stratified into the untreated ‘control group’ (n=17) and ‘treated group’ (n=24). The clinical features, treatment outcome and prognosis including patient survival were analyzed. Results: The mean age of the total patients was 55 years (male:female, 33:8). The most common cause of HCC was a hepatitis B virus infection (85.4%), followed by a hepatitis C virus infection (7.4%). According to the Child-Pugh classification, 24 patients were Child-Pugh class A (58.5%), 15 were Child-Pugh class B (36.6%), and 2 were Child-Pugh class C (4.9%). Lung metastases were identified in 10 patients (24.5%). The treatment modalities of the treated group included 11 systemic chemotherapy regimens (5-FU and cisplatin), 10 transarterial chemotherapy regimens, 2 chemoradiation procedures and 1 hepatic resection. The overall survival was 3.0 months (range, 1-29 months). The 6 month survival rate was 23.5% (4/17) in the control group and 29.2% (7/24) in the treated group. The 12 months survival rate was 0% (0/17) and 25.0% (6/24), respectively. Independent prognostic factor affecting the survival was whether or not any treatment had been carried out. Conclusions: Although the prognosis of advanced HCC with IVC invasion or a right atrial tumor thrombi is poor, treatment might improve the survival rate. (Korean J Hepatol 2007;13: 387-395)

Expression of Caveolin in Hepatocellular Carcinoma: Association with Unpaired Artery Formation ...
Background/Aims: Hepatocellular carcinoma (HCC) is becoming one of the common malignant tumors worldwide, and it is characterized by its high vascularity. Caveolin is the major structural protein in caveolae, which are small omega-shaped invaginations within the plasma membrane. Caveolin has been implicated in mitogenic signaling, oncogenesis and angiogenesis. The expression of caveolin-1 and -2 in HCC and its potential relationship with angiogenesis has not been examined. Methods: Paraffin sections of 35 HCC specimens were immunostained with caveolin-1, caveolin-2, alpha-smooth muscle actin, and CD34 antibodies. In addition, the expression of caveolin-1 and -2 mRNA in HCC was examined. The relationship between the radiological findings and the number of unpaired arteries and microvessel density (MVD) was also investigated. Results: Caveolin-1 and -2 were expressed in the sinusoidal endothelial cells in 20 out of 35, and 18 out of 35 HCC specimens, respectively. Caveolin-1 and -2 were also expressed in the smooth muscle cells of the unpaired arteries in 26 out of 35, and 18 out of 35 HCC specimens, respectively. Increased expression of caveolin-1 and -2 mRNA was detected in 26.7% and 33.3% of the tumor specimens, respectively, compared with the corresponding non-tumorous adjacent liver tissues. There was a significant correlation between expression of caveolin-1, -2 in the smooth muscle cells of unpaired arteries and the number of unpaired arteries. The number of unpaired arteries in HCCs was found to be associated with the degree of contrast enhancement in the arterial phase imaging. However, it did not correlate with the degree of MVD. Conclusions: These findings suggest that the expression of caveolin-1, -2 is associated with the formation of unpaired arteries in HCC. In addition, there is a correlation between the degree of contrast enhancement of the HCC in the arterial phase image and the number of unpaired arteries. (Korean J Hepatol 2007;13:396- 408)

A Case of Abscess Caused by Toxocara
Toxocariasis is a helminozoonosis caused by the infection of a human host by the larva of Toxocara canis and Toxocara catis, which are common nematodes in dogs and cats, and occurs more frequently in school age children. Toxocariasis shows variable clinical manifestations including hepatomegaly, bronchial asthma, uveitis, central nervous system symptoms with peripheral eosinophilia and an increased total serum IgE level. However a hepatic abscess caused by toxocara infection in adults is rare. We experienced a case of heavy alcoholic patients with a hepatic eosinophilic abscess caused by toxocara infestation, which was confirmed by microscopic examination of liver biopsy, enzyme-linked immunosorbent assay test, abdominal CT and the ultrasonography findings. (Korean J Hepatol 2007;13:409-413)

Alfuzosin-induced Acute Liver Injury
We describe a 56-year-old man who developed an acute liver injury after taking alfuzosin for 1 month to control his newly diagnosed benign prostatic hypertrophy (BPH). There was no history of alcohol consumption or the taking herbal or traditional remedies. Viral causes, autoimmune hepatitis, and biliary tree obstruction were excluded. Other rare causes of hepatitis such as hemochromatosis, primary biliary cirrhosis and Wilson’s disease were also absent in this patient. His liver test results began to improve after discontinuing the alfuzosin. Two weeks later, alfuzosin was administered again because the patient complained of dysuria. After 10 days of alfuzosin reuse, his liver test results worsened. Five months later after the complete discontinuation of the drug, his liver test results had returned to normal. This clinical sequence suggests that alfuzosin caused his acute liver injury. (Korean J Hepatol 2007;13:414-418)

A Case of Vasculitis in Chronic Hepatitis C Patient Treated with Pegylated Interferon Alpha-2a ...
There has been an increase in the number of patients treated with pegylated interferon (PEG-IFN) and ribavirin due to the better antiviral efficacy. The main serious adverse events of PEG-IFN plus ribavirin combination therapy are bone marrow suppression and hemolytic anemia. However, there are few reports of vasculitis occurring during PEG-IFN therapy. We describe a patient who developed vasculitis during the treatment of chronic hepatitis C with PEG-IFN and ribavirin. (Korean J Hepatol 2007;13:419-422)

Intrahepatic Cholangiocarcinoma associated with Hepatolithiasis

Yoon Mi Jeen , So Young Jin

Well-differentiated Hepatocellular Carcinoma

Joon Koo Han , Soo Jin Kim , Se Hyung Kim

The Korean Journal of Treatment of Chronic Hepatitis C Virus Infection in Older Adults

Ju Hyun Kim

Review: Analysis of Survival Rate and Prognostic Factors of Intrahepatic Cholangiocarcinoma: ...

Woo Jin Lee , Joong Won Park

Clinical Application of Non-invasive Diagnosis for Hepatic Fibrosis

Sung Won Cho , Jae Youn Cheong
Progressive hepatic fibrosis with development of cirrosis is a feature of chronic liver disease. Assessing fibrosis is important for predicting disease progression and patient management. Liver biopsy is the current gold standard for the diagnosis of liver fibrosis. However, liver biopsy is an invasive procedure. Alternative non-invasive methods have been developed. Serum markers are useful in predicting liver cirrhosis, but accuracy of serum markers is not satisfactory in the assessment of fibrosis. Newly developed transient elastography (Fibroscan) is a non-invasive method of measuring liver stiffness. Fibroscan has been reported to be superior in early detection of cirrhosis to serum markers. Factors influencing it’s performance are not fully investigated. The evaluation of new tests should be continued to perform. (Korean J Hepatol 2007;13:129-137)

Role of Liver Biopsy in the Assessment of Hepatic Fibrosis -Its Utility and Limitations

So Young Jin
Hepatic fibrosis and cirrhosis are the consequences of many types of chronic liver disease. The precise quantification of fibrosis is important to predict the prognosis and monitor the response of treatment modality. The liver biopsy has a role to estimate the stage of fibrosis. However, its sensitivity is below 80%. Its use is limited by sampling errors, inter- and intraobserver variability and possible morbidity and mortality. There is increasing attention to developing clinical algorithms and new noninvasive alternative techniques to predict the stage of fibrosis. However none of these can replace the utility of liver biopsy in the intermediate stage of hepatic fibrosis. Therefore, the liver biopsy is still the “gold standard” to assess the precise stage of hepatic fibrosis. (Korean J Hepatol 2007;13:138-145)

Clinical Outcomes of Lamivudine Therapy in HBeAg Positive Chronic Hepatitis B with Minimally ...
Background/Aims: The aim of this study was to compare the efficacy of lamivudine therapy between chronic hepatitis B (CHB) patients, whose ALT levels less than 2 times the upper limit of normal (ULN) and patients whose ALT levels are more than 2 times ULN. Methods: We retrospectively analyzed 508 consecutive patients with HBeAg-positive CHB who were treated with lamivudine for 1 year or more. Forty-six patients (Group A) with pretreatment ALT levels less than 2 times ULN were retrospectively compared with 462 patients (Group B) whose ALT levels are more than 2 times ULN. Results: HBeAg seroconversion was achieved in 15 (32.6%) of group A and 162 (35.1%) of group B. The cumulative rates of HBeAg seroconversion in group A and B were 19% and 21% at 12 months; 35% and 31% at 24 months; and 38% and 39% at 36 months, respectively. HBV breakthrough was observed in 20 (43.5%) of group A and 192 (41.6%) of group B. The cumulative breakthrough rates of group A and B were 18% and 12% at 12 months; 33% and 29 % at 18 months; 45% and 42% at 24 months, respectively. Post-treatment relapse in group A and B occurred in 56% (5/9) and 41% (44/108), respectively. Therefore, the rates of the HBeAg seroconversion, breakthrough, and post-treatment relapse were not significantly different between these two groups. Conclusions: Lamivudine therapy in HBeAg-positive CHB patients whose ALT levels are minimally elevated is as effective as in treatment of the patients whose pretreated ALT levels are twice more than ULN. (Korean J Hepatol 2007;13:146-156)

Predictors of Lamivudine Resistance in Patients with Chronic Hepatitis B Virus Infection
Background/Aim: Drug resistance is a major concern during nucleos(t)ide analogues therapy in patients with chronic hepatitis B virus (HBV) infections. The aim of this study was to measure the risk of lamivudine resistance provided for each predictive factor in patients with chronic HBV infections. Methods: A total of 183 patients were analyzed among 315 patients with chronic HBV infections enrolled in a tertiary referral hospital between January 2001 and December 2003 on this retrospective cohort study. AST/ALT, HBeAg/anti-HBe, serum HBV DNA levels were tested for every 3 or 6 months. HBV DNA level was tested using Cobas Amplicor HBV Monitor test™. Viral breakthrough was defined as HBV DNA ≥ 5 log10 copies/mL on two consecutive visits in patients who, on treatment, achieved HBV DNA < 5 log10 copies/mL. The risk of viral breakthrough was measured using Cox proportional hazards model for variables: age, sex, BMI (kg/m2), baseline ALT, HBeAg positivity, baseline HBV DNA level, serum HBV DNA level at 6 month of lamivudine therapy. Results: The cumulative rates of viral breakthrough were 9.6%, 39.0%, 55.8% at 12, 24, 36 months, respectively. Serum HBV DNA level of 6 month of lamivudine therapy and presence of HBeAg were independent predictors for viral breakthrough. The relative risk was 1.43 (95% C.I. 1.09-1.89, P=0.010) for serum HBV DNA level at 6 months of lamivudine therapy and 1.77 (95% C.I. 1.06-2.95, P=0.029) for presence of HBeAg. Conclusions: Serum HBV DNA level at 6 months of therapy and HBeAg positivity were predictors of early lamivudine resistance in patients with chronic HBV infections. An alternate therapy should be considered when serum viral load is high at 6 months of lamivudine therapy. (Korean J Hepatol 2007;13:157- 165)

Clinical Features of Acute Viral Hepatitis A Complicated with Acute Renal Failure
Background: Most patients with acute viral hepatitis A (AVHA) spontaneously recover, but a few patients experience complications. This study was carried out to examine clinical features of AVHA complicated with acute renal failure (ARF). Method: Medical records of 404 patients with AVHA were reviewed. Clinical features of AVHA patients with ARF (group A) were compared with those of AVHA patients without ARF (group B). Result: ARF complication was present in 11 patients (3%). There were no differences between group A and B in sex ratio and age. Microscopic hematuria (7 cases), proteinuria (7 cases), metabolic acidosis (4 cases), oliguria (4 cases), pulmonary edema (3 cases) and hyperkalemia (2 cases) were found in group A. The prevalence of heavy alcohol drinking (64% vs 3%, p<0.001) and diabetes mellitus (18% vs 1%, p=0.01) was higher in group A than B. The peak value of ALT (median: 4,290 IU/L vs 1,266 IU/L, p=0.006) and total bilirubin (median: 10.8 mg/dL vs 6.0 mg/dL, p=0.001) was higher in group A than B. Duration of admission was longer in group A than B (median: 14 days vs 5 days, p<0.001). Four patients of group A recovered with renal replacement therapy, while 7 patients recovered with conservative treatment. Conclusions: The AVHA patients with ARF experienced more severe hepatitis than those without ARF, but they had a good prognosis with the proper treatment. (Korean J Hepatol 2007;13:166-173)

The Prevalence of Peripheral Iron Overload and the Presence of HFE gene (H63D) Mutation among ...
Backgrounds/Aims: There are controversies on the role of iron overload in the mechanism of liver injury in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the prevalence of peripheral iron overload, and to study the presence of HFE mutations (C282Y, H63D, S65C) in a cohort of Korean NAFLD patients. Methods: 255 patients with NAFLD were included. The patients had been diagnosed as having NAFLD by the criteria of elevated aminotransferase levels, compatible ultrasonographic findings and exclusion of other etiologies. Blood samples were tested for chemistry, iron profile, and mutational analysis for HFE gene (C282Y, H63D, S65C). Results: Of the 255 NAFLD patients, the prevalence of peripheral iron overload was 19.2% according to the cutoff level of transferrin saturation (TS) > 45%, and 3.9% of NAFLD patients were having hyperferritinemia over 400 ng/mL. Hyperferritinemia was significantly associated with elevated serum levels of fasting glucose, AST and TS. We found the presence of H63D mutation, either heterozygote or homozygote, among the NAFLD patients with peripheral iron overload. Conclusions: The prevalence of peripheral iron overload in the Korean NAFLD patients was not rare, and the presence of H63D mutation among NALFD patients was identified. Further studies on the significance of iron overload or HFE mutation in the pathogenesis of NAFLD are needed. (Korean J Hepatol 2007;13:174-184)

Etiologic and Laboratory Analyses of Ascites in Patients who Underwent Diagnostic Paracentesis
Background/Aims: Liver cirrhosis and malignant tumors are two major causes of ascites according to the reports from Western countries, 80% and 10% respectively. Assuming that there might be regional differences in etiologies and changes in their frequency over time, we investigated causes of ascites and the diagnostic usefulness of various laboratory tests. Methods: Medical records of 366 patients, who underwent diagnostic paracentesis in the mid-1990s (1996 and 1997) and early 2000s (2001 and 2002), were retrospectively reviewed. The etiology was confirmed by histology, imaging studies, and ascites analyses. Results: The frequency of cirrhotic ascites was 59.6%, cancer-related 25.7%, tuberculous peritonitis 6.6%, and others 8.1%. Among cirrhotics, the frequency of cases related to hepatitis B decreased significantly from 72% to 55% over time, and alcoholic cirrhosis increased from 18% to 34%. Among cancer-related ascites, peritoneal carcinomatosis type was 75.5% (primary sites: stomach 24.5%, pancreas 15.9%, colon 15.9%, lung 7.4%, etc), metastatic liver cancers 8.5%, hepatocellular carcinoma without cirrhosis 6.4%, etc. The sensitivity of serum-ascites albumin gradient for the diagnosis of cirrhotic ascites was 91.4%, and total protein in ascites also revealed a comparable diagnostic sensitivity, 90%. The diagnostic sensitivity of adenosine deaminase for tuberculous peritonitis was 94.2%, and its positive predictive value was 75%. Conclusions: Liver cirrhosis is the leading cause of ascites, especially alcoholic cirrhosis has significantly increased. The next common etiology is cancer-related, and its frequency in Korea is higher than in western countries. Tuberculous peritonitis is still prevalent, and adenosine deaminase could precisely differentiate it from other causes. (Korean J Hepatol 2007;13:185-195)

Evaluation of Predictive Value of Okuda, TNM, CLIP and JIS Staging Systems for Hepatocellular ...
Background/Aims: The aims of this study were to validate the prognostic value of the JIS score for HCC and to compare discriminatory ability and predictive power with other staging systems such as Okuda, TNM and CLIP. Methods: We analyzed the clinical records of 210 patients who were diagnosed as HCC from 2000 to 2002. Univariate and multivariate survival analyses were done to find out factors to affect survival. To validate prognostic value of those staging systems, survival curve was obtained and analyzed by the Kaplan-Meier’s method, and to compare discriminatory ability and predictive power, Homogeneity LR X² test and AIC score were used. Results: The median survival was 19.5 months (19.1±14.9). The number of patients and 3-year survival rate for those staging systems were Okuda 1(126, 57.7%), 2(63, 9.0%) and 3(21, 0.0%) (p<0.001); TNM I (34, 63.1%), II (71, 59.4%), III (50, 22.4%), IV-A (6, 14.3%) and IV-B (1, 6.5%) (p<0.001); CLIP 0 (79, 68.5%), 1 (39, 34.2%), 2 (36, 16.7%), 3 (25, 20.0%), 4 (18, 5.1%), 5 (9, 11.1%) and 6 (4, 0.0%) (p<0.001) and JIS 0 (26, 78.9%), 1 (65, 65.3%), 2 (43, 21.9%), 3 (40, 25, 8.0%) and 5 (11, 2.0%)(p<0.001) in univariate analysis using Kaplan-Meier analysis. Homogeneity LR X² test showed more stratification power in JIS (Okuda, 102.8; TNM, 128.2; CLIP, 148.4 and JIS, 185.6) and AIC score showed superior predictive power in JIS system (Okuda, 1228.5; TNM, 1130.3; CLIP, 1117.1 and JIS, 1093.6). Conclusions: The proposed JIS system is useful system to predict survival of HCC patients. The discriminate ability of the JIS score is much better than other staging systems and has better prognostic predictive power compared to other staging systems. (Korean J Hepatol 2007;13:196-207)

Analysis of Survival and Factors Affecting the Survival after Surgical Resection of Peripheral ...
Backgrounds/Aims: Although the survival rate after surgical resection of peripheral cholangiocarcinoma is low, surgical resection is only potentially curative therapy. The aim of this study is to evaluate clinicopathological factors affecting survival after surgical resection of peripheral cholangiocarcinoma. Methods: Between February 1990 and December 2005, surgical intervention with curative intent was performed on 318 patients and 292 patients underwent resection. We retrospectively analyzed survival data of 318 patients and clinicopathological factors affecting survival by reviewing the medical record. Results: Among the 292 cases of resection, curative resection with tumor-free margin (R0) has been resulted in 221 cases. The 1-, 3-, 5- and 10-year survival rate of R0 resection were 74.9, 46.9, 36.9 and 15.2%, respectively. The survival rate of patient undergoing R0 resection was significantly better than that of R1, R2 or nonresection. Multivariate analysis showed that curative resectability, macroscopic type of tumor and lymph node metastasis were statically significant independent prognostic factors. Conclusions: The survival after surgical resection of peripheral cholangiocarcinoma depends on curability of surgical resection, macroscopic type of tumor and status of lymph node. Particullary in R0 resection for intraductal growth type without lymph node metastasis, there is great chance for long-term survival. Surgical resection attaining tumor free margin should be attempted if liver function and general condition of patient are acceptable for hepatectomy. (Korean J Hepatol 2007;13:208-221)

Carcinoma with Predominant Lymphoid Stroma in Hepatobiliary System -Report of 2 Cases-

Hye Sook Min , Eun Shin , Ja June Jang
Lymphoepithelioma-like carcinoma (LELC) is an undifferentiated carcinoma with predominant lymphocytic infiltration, which is associated with Epstein-Barr virus (EBV) in variable proportions. We report two cases of carcinoma with predominant lymphoid stroma in hepatobiliary system. The first case was a lymphoepithelioma-like undifferentiated carcinoma with focal differentiation of cholangiocarcinoma (cytokeratin 19+) and hepatocellular carcinoma in light microscopy. The infiltration of CD8+ T lymphocytes was observed in the tumor and the surrounding hepatic parenchyme. In this tumor, EBV was detected and LMP1 was positive immunohistochemically. The second case showed the mixed features of lymphoepithelioma-like carcinoma and cholangiocarcinoma with predominant lymphoid stroma. In this case, EBV was detected. LELC of hepatobiliary system is an entity distinguished from conventional carcinoma with lymphoid stroma, and its association with EBV warrants further research. (Korean J Hepatol 2007;13:222-227)

A Case of Acute Hepatitis A Complicated by Guillain-Barre Syndrome
We report here a case of acute hepatitis A, which was complicated by Guillain-Barré syndrome (GBS). A 32-year old male admitted to our hospital with the symptoms of acute hepatitis and was diagnosed to have acute hepatitis A with positive IgM anti hepatitis A virus antibody. On 9th day after the onset of jaundice, acute progressive, ascending, symmetric motor paralysis were developed and eventually respiratory failure ensued. Cerebrospinal fluid analysis showed albumino-cytologic dissociation and nerve conduction velocity test suggested a polyradiculopathy. He was diagnosed to have GBS and treated with intravenous immunoglobulin and required a ventilatory support. After 90 hospital days, he recovered in ambulatory condition with the aid of crutches. The clinical course, prognosis and the outcome of neuropathic symptoms of GBS following acute hepatitis A were relatively poor in our case. (Korean J Hepatol 2007;13:228-233)

A Case of Metastatic Cutaneous Nodules of Recurrent Hepatocellular Carcinoma
Common metastaic sites of hepatocellular carcinoma include lung, peritoneum, adrenal gland and bone, but rarely, skin can be metastatic sites. Although hepatocellular carcinoma is the third commonest malignancy in Korea, cutaneous metastasis from hepatocellular carcinoma was rarely reported. Cutaneous metastasis from malignant neoplasm of the internal organ occur at the variable stage and the growth pattern of cutaneous lesions is nonspecific and various, so the differential diagnosis of skin lesions must be considered to other malignant condition. We report a case of cutaneous metastasis from recurrent hepatocellular carcinoma that was confirmed by skin biopsy with immunohistochemical stain. (Korean J Hepatol 2007;13:234-238)

Papillary Cholangiocarcinoma Arising from Biliary Papillomatosis

Yoon Mi Jeen , So Young Jin

Intraductal Papillary Mucinous Cholangiocarcinoma

Joon Koo Han , Se Hyung Kim , Soo Jin Kim

The Korean Journal of Does Smoking Affect the Liver?

Neung Hwa Park

2007 EASL Topics : Post EASL Reflexion

Kyu Sung Rim

2007 EASL Topics : Topics Related to Hepatitis B

Sang Hoon Ahn

2007 EASL Topics : Topics Related to Therapy of Hepatitis B

Jong Eun Yeon

2007 EASL Topics : Topics Related to Hepatitis C

So Young Kwon

2007 EASL Topics : Topics Related to Therapy of Hepatitis C

Youn Jae Lee

2007 EASL Topics : Topics Related to NAFLD

Young Han Paik

2007 EASL Topics : Topics Related to Alcoholic Liver Disease

Jin Mo Yang

2007 EASL Topics : Topics Related to Liver Cirrhosis

June Sung Lee

2007 EASL Topics : Topics Related to Clinical Research of Hepatocellular Carcinoma

Il Han Song

2007 EASL Topics : Topics Related to Liver Transplantation

Jeong Won Jang

Changes in the Seroprevalence of Hepatitis A Virus Antibody in Korea

Jae Hong Park

Assessment of Health-related Quality of Life in Patients with Chronic Liver Disease

Sang Hwa Urm

Hypoxia in Hepatocellular Carcinoma

Sun Jung Myung , Jung Hwan Yoon
Hepatocellular carcinoma (HCC) is characterized by hypervascularity, indicating that angiogenesis plays a vital role in HCC growth and progression. A number of anti-angiogenic therapies are being utilized in clinical trials in patients with HCC. However, the therapeutic efficacy of anti-angiogenic monotherapy is still insufficient. While inhibition of angiogenesis results in tumor hypoxia and cell death, this inhibition may also activate hypoxia-induced cell signals that may promote HCC progression. Therefore, an understanding of these signals may be essential in designing efficient anti-angiogenic therapies. This review summarizes the role of hypoxia-induced signals in HCC. (Korean J Hepatol 2007;13:9-19)

Cirrhotic Cardiomyopathy

Moon Young Kim , Soon Koo Baik
Most patients with liver cirrhosis have hyperdynamic circulatory alterations with increased cardiac output, and decreased systemic vascular resistance and arterial pressure. But, in spite of the increased resting cardiac output, ventricular contractile response to stressful stimuli is attenuated in cirrhotic patients which is termed as cirrhotic cardiomyopathy. The prevalence of cirrhotic cardiomyopathy remains unknown at present. Clinical features include structural, histological, electrophysiological, systolic and diastolic dysfunction. Multiple factors are considered as responsible, including impaired β-adrenergic receptor signal transduction, abnormal membrane biophysical characteristics, and increased activity of cardiodepressant systems mediated by cGMP. Generally, cirrhotic cardiomyopathy with overt severe heart failure is rare. However, major stresses on the cardiovascular system such as liver transplantation, infections and insertion of transjugular intrahepatic portosystemic shunts (TIPS) can unmask the presence of cirrhotic cardiomyopathy and thereby convert latent to overt heart failure. Cirrhotic cardiomyopathy may also contribute to the pathogenesis of hepatorenal syndrome and circulatory failure in liver cirrhosis. Because of the marked paucity of treatment studies, current recommendations for management are empirical, nonspecific measures. Further studies for pathogenesis and new therapeutic strategies in this area are required. (Korean J Hepatol 2007;13:20-26)

The Age-specific Seroprevalence of Hepatitis A Virus Antibody in Korea

Sat, 01 Jan 2000 00:00:01 +0100
Backgrounds/Aims: The epidemiology of hepatitis A is associated with socioeconomic and hygiene status. Recently, the prevalence of hepatitis A in young adults has been steadily increasing in Korea. This study is to investigate the age-specific seroprevalence of hepatitis A virus in Korea. Methods: Stored sera from 250 healthy adult subjects who visited the health promotion center in Samsung Medical Center between July and August 2006 were tested for IgG hepatitis A virus antibody (anti-HAV). Results: The prevalence of anti-HAV was 2%, 72%, 92%, 94%, 100% in 20’s, 30’s, 40’s, 50’s, and 60’s, respectively. The prevalence of anti-HAV was significantly lower in subjects below age 40 compared to those above 40 (37.0% vs. 95.3%, p<0.001). The seroprevalence was higher in area outside of Seoul compared to those living in Seoul in age group below 40 (25.6% vs. 55.6%, p=0.01). In Seoul area, the prevalence was significantly lower in Kangnam-Gu, Seocho-Gu, and Songpa-Gu district compared to the other areas of Seoul in the age group below 40 (20.0% vs. 42.1%, p<0.05). Conclusion: The seroprevalence of hepatitis A virus antibody in Korean population below 40 is quite low and immunity to hepatitis A virus in those subjects can be a public health issue. In view of changing seroepidemiology, a policy for hepatitis A vaccination in population below 40 might be warranted. (Korean J Hepatol 2007;13:27-33)

The Survey for the Actual Condition of Drug Medication and Development of Health Care Cost ...

Sat, 01 Jan 2000 00:00:01 +0100
Backgrounds/Aims: In Korea, interests in health and health care costs have been increased along with the increase of mean survival rate and income level. The aim of this study is to investigate the actual condition of drug medication and burden of health care cost. Methods: A total of 1,434 subjects in four tertiary medical centers were enrolled in this study. The questionnaires were obtained between March 2005 and September 2005. Based on this information, the actual condition of drug medication and health care cost were analyzed. Results: The mean age of the subjects was 55.0±11.4 years (16-87 years). The male and female ratio was 1.74:1. The subjects with drug medication except for doctor’s prescription are presently 26.6% and were 40.9% in the past. Traditional medicine (39.6%) and health food (29.9%) are more frequently used than herbal medicine (5.8%) and medical supplies (4.2%) now. In the past, herbal medicine (14.6%) was more frequently used compared with the present. The side effects of drug medication were developed in 90 subjects (7.5%). The total mean health care costs were 895,000 won/year, the herbal medicine, 834,000 won/year, the health food, 950,000 won/year, and the traditional medicine, 324,000 won/year. Conclusions: In this study, the subjects with other drug medications without doctor’s prescription were as high as ever. The frequency of the use of the herbal medicine was decreased. However, the frequency for the use of the health food and traditional medicine have relatively increased. The side effects and additional large amounts of health care costs were occurred. (Korean J Hepatol 2007;13:34-43)

Validation of the Korean Version of Liver Disease Quality of Life (LDQOL 1.0) Instrument
Background/Aims: Assessment of Health-related quality of life (HRQOL) outcomes in treatment of chronic disease is increasingly important. The objective of this study was to validate a Korean translation of the Liver Disease Quality of Life instrument (LDQOL version 1.0) for use in patients with chronic liver disease. Methods: Two native Korean speakers with fluent English translated LDQOL including instructions, items, and response choices. This Korean translation of the LDQOL was administered to 121 patients with chronic liver disease. Cronbach's alpha coefficients were applied to test an internal consistency reliability of disease-specific scales of the LDQOL. MELD and modified CTP scores were calculated for all patients. Associations of MELD and modified CTP scores with severity of liver disease were analyzed with LDQOL. Results: Internal consistency reliability was good (Cronbach's Alpha=0.69-0.94) in liver disease specific scales, except for the quality of social interaction scale (Cronbach's Alpha= 0.56). Mean modified CTP score and MELD score were 6.2±1.9 and 9.3±5.3, respectively. Both MELD score and modified CTP score showed correlations with most of the scores of liver disease specific scales of LDQOL 1.0, except for the quality of social interaction and sleep scale. Conclusions: The Korean version of the liver disease specific scales of the LDQOL 1.0 is validated and useful for measuring HRQOL in Korean patients with chronic liver disease. (Korean J Hepatol 2007;13: 44-50)

Usefulness of
Background/Aims: There are many models for predicting prognosis of liver cirrhosis including Child Turcotte Pugh (CTP), the model for end-stage liver disease (MELD) score and its changes over time (ΔCTP and ΔMELD/month). We investigated the ability of these models to predict the mortality of liver cirrhosis patients with the first episode of variceal bleeding and which model can be usefully applied in practice. Methods: Seventy-one liver cirrhosis patients hospitalized for the first episode of esophageal variceal bleeding were retrospectively analyzed. The predictive power of initial CTP, MELD score, ΔCTP and ΔMELD/month was compared through c-statistics and multiple logistic regression. Results: All of the prognostic predictors measured higher in patients who survived than in those who died. The area under the receiver operating characteristic (ROC) curve for ΔMELD/month in 6 months was 1, a higher value than 0.81 for initial CTP, 0.75 for initial MELD, and 0.84 for ΔCTP/month; the area of ΔMELD/month in 12 months was 0.81, also showing a higher value than others. ΔMELD/month > 0.27 was a strong significant prognostic predictor in 6 (odds ratio: 40.1, p=0.001) and 12 months (odds ratio: 14.1, p<0.001). Only the ΔMELD/month was an independent prognostic predictor with a risk ratio of 1.604 (95% CI: 1.119-2.302, p=0.01) in 6 months and 1.627 (95% CI: 1.294-2.047, p<0.001) in 12 months. Conclusions: The ΔMELD/month is superior to initial CTP, MELD and ΔCTP/month to predict 6 and 12 months mortality in liver cirrhosis patients with the first episode of variceal bleeding. (Korean J Hepatol 2007;13:51-60)

Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-Ligated Rats
Backgrounds and Aims: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. Material and methods: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. Alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. Results: Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (μg/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA. Conclusions: Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats. (Korean J Hepatol 2007;13:61-69)

Expression of ErbB Receptor Proteins and TGF-

Tae Yeong Lee , Kyoung Tae Kim , Sang Young Han
Background/Aims: ErbB receptor proteins are transmembrane tyrosine kinase receptors; when they are activated by interaction with ligands, they generate diverse cellular responses, especially during lesion development and progression to cancer. In this study the expression of ErbB receptors and TGF-α were investigated using an experimental cirrhosis rat model giving rise to hepatocellular neoplasms, similar to human liver diseases. Methods: Fifty three male rats received intraperitoneal injection of diethylnitrosamine (DEN, 50 mg/kg), weekly for 18 weeks. Until the eighth week, two rats were sacrificed every two weeks and from the tenth to the eighteenth week, five rats were sacrificed weekly. Grossly, dyschromatic and dysmorphic nodules were counted and categorized into three groups: N1/N2/N3: 3 mm≤x<5 mm/5 mm≤x<10 mm/x≥10 mm in diameter. All nodules were examined, histologically. Antibodies for GSTp, TGF-α, EGF-R, ErbB2, ErbB3 and ErbB4 were used for immunohistochemistry. Results: The onset of cirrhoses was noted from the twelfth week. Preneoplastic foci, hepatocellular adenomas (HCA) and hepatocellular carcinomas (HCC) were noted from the second, eleventh and fifteenth week, respectively. The nodules (N1/N2/N3: 397/258/64) included regenerating nodule; RN (N1/N2/N3: 72.3%/15.9%/0%), HCA (N1/N2/N3: 27.2%/82.2%/7.6%) and HCC (N1/N2/N3: 0.5%/ 1.9%/92.4%). EGF-R was expressed in 12.5% of RN, 64.7% HCA and 75.2% HCC. TGF-α was expressed in 92.4% of RN, 91.3% HCA and 93.2% HCC. Sixty eight percent of TGF-α expressing nodules showed concurrent EGF-R expression. ErbB2 was expressed in 83.6% of RN, 72.9% HCA and 88.7% HCC. ErbB4 was expressed in 95.2% of RN, 86.3% HCA and 62.5% HCC. Conclusions: Increased expression of EGF-R and decreased expression of ErbB4, might be related with tumor progression during DEN-induced hepatocarcinogenesis. (Korean J Hepatol 2007;13:70-80)

Expression of G1 Cell Cycle Regulators in Rat Liver upon Repeated Exposure to Thioacetamide

Kyoung-Tae Kim, M.D., Sang-Young Han, M.D., Ph.D., Jin-Sook Jeong, M.D., Ph.D.1
Background/Aims: Eukaryotic cell cycle is regulated by signal transduction pathways mediated by complexes of cyclin dependent kinases (CDKs) and their partner cyclins, or by interaction with CDK inhibitors. Thioacetamide (TA) is a weak hepatocarcinogen causing several types of liver damage in a dose dependent manner and ultimately producing malignant transformation. We investigated alterations of expression of cell cycle regulators in the rat liver, involved in G1 entry and progression during TA administration. Methods: We studied expression patterns of cyclin D1, CDK4, CDK6, p21^CIP1 and p16^INK4a during daily intraperitoneal injection of low dose TA (50 mg/kg) till 7 day. We used western blot and immunohistochemistry for detection. Results: Expression of cyclin D1, CDK4, CDK6 and p21^CIP1 increased from 6 hour and peaked at 2, 3 day, then decreased next 2 days, and re-increased at 6 day. Cytoplasmo-nuclear translocation of cyclin D1 and p21^CIP1 was evident within 1 day and prominent at 2 and 7 day. Expression of p16^INK4a increased immediately after TA treatment and remarkably increased from 3 day and progressed till 7 day, showing cytoplasmic location, suggestive of inactive form. Most of in situ immunoreactions occurred at the centrilobular hepatocytes. Concomitant nuclear translocation of p21^CIP1 and cyclin D1, different with p16^INK4a suggests that p21^CIP1 might be a transporter for nuclear translocation rather than cell cycle inhibitor. Conclusions: Daily administration of low dose TA makes cell cycle open and G1 progress, possibly due to cyclin D1, CDK4 and CDK 6, their transporter p21^CIP1, and inactive p16^INK4a, which occur at quiescent hepatocytes, not stem cells. (Korean J Hepatol 2007;13:81-90)

Gastric Metastasis of Hepatocellular Carcinoma Treated by Transarterial Chemoembolization: A ...
Extrahepatic metastasis in patients with hepatocellular carcinoma (HCC) occurs frequently. The most common site of metastasis is the lung, followed by regional lymph nodes and bones. However, gastrointestinal metastasis of HCC is a rare condition and solitary polypoid metastatic lesion on stomach without any evidence of direct invasion from primary mass is very rare. These metastatic lesions are usually asymptomatic, and most are discovered at postmortem examination or are found incidentally during laparotomy. The choice of treatment for gastrointestinal metastatic lesion of HCC includes surgery, transarterial chemoembolization, and local injection but the treatment is often difficult and unsuccessful. We report a case of 69 years old man who presented disappearance of a polypoid metastatic lesion of HCC on the gastric fundus by transarterial chemoembolization. (Korean J Hepatol 2007;13:91-95)

A Case of the Treatment in an Adult with Hepatic Undifferentiated (Embryonal) Sarcoma
Undifferentiated embryonal sarcoma is a rare primary malignant neoplasm of the liver. Undifferentiated sarcoma of the liver in adult is an uncommon hepatic tumor of mesenchymal origin, generally considered an aggressive neoplasm with an unfavorable prognosis. We present a case of undifferentiated sarcoma in a 61-year-old woman. CT scan demonstrated a large heterogenous, exophytic growing hepatic mass in the right lobe with pulmonary metastatic nodules. US guided liver biopsy was done and pathological findings of the liver specimen revealed that isolated or grouped round pleomorphic cells and spindle to stellate cells were present. Immunohistochemical stain showed that tumor cells expressed positivity for vimentin and partially positivity or negativity for cytokeratin. She was diagnosed as having undifferentiated sarcoma of the liver. She received seven courses of VAIA chemotherapy by CWS protocols. Chemotherapy was efficacious and the size of the tumor decreased considerably after the treatment. No tumor recurrence for 12 months is noted. (Korean J Hepatol 2007;13:96-102)

Pulmonary Toxicity by Pegylated Interferon
The combination therapy with pegylated interferon α and ribavirin has increasingly prescribed for chronic hepatitis C. Although many side effects of interferon such as flu-like symptoms, gastrointestinal and neuropsychiatric symptoms are well known, only several cases of interferon-induced pulmonary toxicity have been reported. Interferon-induced pulmonary toxicity usually develops from 2 weeks to 12 weeks after treatment for HCV infection. Diagnosis is commonly based on clinical findings such as a dry cough, dyspnea, hypoxemia, and a restrictive pattern in pulmonary function testing, bilateral diffuse parenchymal infiltrations, histopathological findings of interstitial pneumonitis, and exclusion of any other causative agents. Prompt withdrawal of the drug is the cornerstone of treatment. We report a case of PEG-IFN α-2a induced pulmonary toxicity in a 50-year-old male patient with hepatitis C. To our knowledge, this is the first case of pegylated interferon α-2a induced pulmonary toxicity in Korea. (Korean J Hepatol 2007;13:103-107)

Bile Duct Cystadenocarcinoma

So Young Jin

Combined Hepatocellular-cholangiocarcinoma

Joon Koo Han , Se Hyung Kim , Soo Jin Kim

The Korean Journal of Use of Google as a Diagnostic Aid

Kwang Cheol Koh
Objective: To determine how often searching with Google (the most popular search engine on the world wide web) leads doctors to the correct diagnosis. Design: Internet based study using Google to search for diagnoses; researchers were blind to the correct diagnoses. Setting: One year’s (2005) diagnostic cases published in the case records of the New England Journal of Medicine. Cases: 26 cases from the New England Journal of Medicine; management cases were excluded. Main outcome measure: Percentage of correct diagnoses from Google searches (compared with the diagnoses as published in the New England Journal of Medicine). Results: Google searches revealed the correct diagnosis in 15 (58%, 95% confidence interval 38% to 77%) cases. Conclusion: As internet access becomes more readily available in outpatient clinics and hospital wards, the web is rapidly becoming an important clinical tool for doctors. The use of web based searching may help doctors to diagnose difficult cases. [Abstract reproduced by permission of BMJ 2006;333:1143-1145]

Sat, 01 Jan 2000 00:00:01 +0100

Changes of MELD: Can Exceed Child-Pugh`s Authority?

June Sung Lee

Preoperative Evaluation and Postoperative Complications with Prognostic Impact of Surgical ...

Koo Jeong Kang

Resistance to Adefovir in Patients with Chronic Hepatitis B

Soo Hyung Ryu, M.D.,* Young-Hwa Chung, M.D. — Sat, 01 Jan 2000 00:00:01 +0100
Adefovir dipivoxil (ADV) is effective in the treatment of chronic hepatitis patients with wild type and lamivudine-resistant hepatitis B virus. The occurrence of viral resistance to long-term adefovir therapy is rare, the cumulative rates of resistance were 0%, 3%, 11%, 18%, and 28% at 1, 2, 3, 4, and 5 years of therapy, respectively. The emergence of adefovir resistant mutant in patients with lamivudine resistance is more common than in treatment-naive patients. Two major mutations of adefovir resistance are rtN236T and rtA181V/T. Other mutations in the HBV polymerase (rtP237H, rtN238T/D, rtV84M, rtS85A, rtV214A, rtQ215S) reduce sensitivity to adefovir, but the significance of these mutations is unclear. The adefovir mutations slightly decrease adefovir susceptibility in vitro, suggesting mild clinical course after the occurrence of adefovir resistance. However, some patients show viral rebound and hepatic decompensation. Lamivudine, entecavir, and tenofovir are used currently for salvage therapy in patients with adefovir resistance. To reduce adefovir resistance, combination therapy with adefovir and lamivudine in patients with lamivudine resistance may be a treatment option. (Korean J Hepatol 2006;12:484-492)

Liver Transplantation for Hepatocellular Carcinoma

Kyung Suk Suh , Nam Joon Yi
Since the hepatocellular carcinoma (HCC) develops in cirrhotic liver and is often multicentric, liver transplantation (LT) seems to be a rational approach for the treatment of HCC. Current selection criteria of LT for HCC are Milan criteria (single nodule ≤ 5 cm , or ≤ 3 nodules and ≤ 3 cm each, without major vessel invasion and metastasis). Four-year survival rate in patients within Milan criteria was 75% after LT, which was comparable with that of transplant candidates without HCC. Expanding selection criteria beyond Milan results in more patients with HCC being cured at the expense of a higher incidence of recurrence. The molecular/biologic information of individual tumors will be useful to reduce the recurrence in the future. Transarterial chemoembolization, local ablative therapy, and even surgical resection can be performed to prevent tumor progression and sometimes provide a chance of biologic selection of HCC while waiting for liver transplantation. In Korea, the cadaver donor shortage is severe and cadaveric liver transplantation for HCC patients is exceptional. Living donor LT is a more popular approach for these patients in Korea. However, many controversial issues have been raised about live donor safety and expansion of criteria in living donor LT. In the future, with better understanding of tumor biology, we could select a better group of patients who would not recur cancer after LT. (Korean J Hepatol 2006;12:493-506)

Clinical Significances of Serum Soluble Fas and Soluble Fas Ligand in Chronic Hepatitis B

Eun Jung Jun, M.D., Joon-Yeol Han, M.D., and Hee Sik Sun, M.D.1
Background/Aims: Apoptosis via Fas/FasL system is thought to be involved in the development of hepatocyte death in viral hepatitis B. In chronic hepatitis C, sFas/sFasL system was reported to control liver injury induced by Fas/FasL mediated apoptosis. To determine the role of sFas/sFasL system in chronic hepatitis B, we analyzed serum sFas/sFasL in 58 HBV patients and 29 healthy controls. Methods: HBV patients were categorized into two groups; normal ALT (≤40 IU/L) and elevated ALT (>40 IU/ L). Serum sFas/sFasL levels in HBV patients were measured by ELISA and was compared with those in 29 healthy controls. Serum ALT levels, histological activity, and Fas/FasL expression of liver were compared. Results: Chronic hepatitis B patients with elevated ALT had significantly higher serum sFas levels than those in healthy controls (P<0.01). Serum sFasL levels, however, were significantly lower than those in healthy controls (P<0.01). Patients with moderate to marked degree of inflammation and fibrosis had significantly higher serum sFas levels than those in healthy controls (P<0.05). Serum sFasL levels had no correlation with the hepatic histological activity. Serum sFas/sFasL levels also had no significant correlation with the Fas/FasL expression of liver. Conclusions: Serum sFas/sFasL levels play a possible role in the pathogenesis of chronic hepatitis B. These results suggest that serum sFas levels might serve as a marker for estimating the degree of hepatic histological activity. (Korean J Hepatol 2006;12:507-514)

Clinical Significance of Intrahepatic HCV RNA Level in Chronic HCV Infection
Background/Aims: This study was carried out to identify the correlation between the serum HCV RNA and the liver HCV RNA level in chronic hepatitis C patients and to evaluate the differences of biochemistry, histology, HCV genotype and their response to antiviral therapy according to intrahepatic HCV RNA levels. Methods: For thirty-six chronic hepatitis C patients (M:F=22:14, CH:LC=27:9), percutaneous liver biopsy was performed, and serum and liver HCV RNA level were measured. Seventeen patients were treated with IFN-α and ribavirin. Results: There was a significant correlation between intrahepatic and serum HCV RNA levels (intrahepatic HCV RNA: 1.9±3.1×107 copies/g vs. serum HCV RNA: 3.2±3.2×106 copies/mL)(r=0.538, P<0.01). Total histological activity score (r=0.346, P=0.04) and periportal inflammation (r=0.398, P=0.01) were correlated with intrahepatic HCV RNA level. However, serum HCV RNA level was not correlated with histological activity. Serum ALT was not correlated with intrahepatic HCV RNA level. Intrahepatic HCV RNA level was higher in genotype 1 than genotype 2 or 3 (P=0.07). Intrahepatic HCV RNA level was not correlated with response to anti-viral therapy. Conclusion: Intrahepatic HCV RNA level was correlated with serum HCV RNA level and periportal inflammation in patients with chronic hepatitis C. It seems that intrahepatic HCV RNA level is more closely related to histological features than serum HCV RNA level. (Korean J Hepatol 2006;12:515-523)

Differential Diagnosis of Diabetes Mellitus caused by Liver Cirrhosis and Other Type 2 Diabetes ...

Min Geun Kim , Won Choong Choi
Background/Aim: The liver plays important roles in the homeostasis of glucose metabolism since it acts as a major target organ for insulin and a site for gluconeogenesis and glycogen storage. Diabetes mellitus (DM) commonly develops in patients with liver cirrhosis as the result of hepatocyte dysfunction and/or inadequate mass. To assess differences between DM due to liver cirrhosis (hepatogenous DM) and the other type 2 DM, we compared the patterns of hyperglycemia and hyperinsulinemia in hepatogenous DM with those observed in type 2 DM. Methods: 18 diabetic patients with liver cirrhosis (caused by alcohol, n=8; HBV, n=5; HCV, n=2; others, n=3) were matched with 18 type 2 diabetic patients without liver cirrhosis for age and gender. None of the patients or controls had been treated with insulin or β-blockers. The level of glycosylated hemoglobin (HbA1C), fasting plasma glucose (FPG), postprandial plasma glucose (PP2h), fasting plasma C-peptide and insulin were measured. Results: The ratio of PP2h/FPG (2.27 vs. 1.69), fasting insulin (23.2: 11.6 ?IU/mL) and HOMA-IR index (8.38 vs. 3.52) were significantly higher in hepatogenous DM than the other type 2 DM (P<0.05). PP2h, fasting C-peptide and ratio of fasting insulin/C-peptide tend to be higher in hepatogenous DM than those of controls, but which were not statistically significant. Conclusions: The ratio of PP2h/FPG and fasting plasma insulin differentiated hepatogenous DM from the other type 2 DM. Insulin resistance in liver cirrhosis was higher than the other type 2 DM, and impaired hepatic insulin degradation might be an important mechanism of hyperinsulinemia in liver cirrhosis. (Korean J Hepatol 2006;12:524-529)

Clinical Usefulness of
Backgrounds/Aims: The change of MELD (Model for End-stage Liver Disease) score over time (ΔMELD) has been proposed as a tool to predict the survival in cirrhotic patients. The aims of the study were to assess ability of the ΔMELD to predict the survival and compare them with the initial MELD and CP score. Methods: MELD score was serially determined at least twice with more than two-month interval in 120 cirrhotic patients. We analyzed the clinical factors associated with the variation of MELD score. The predictive power of 6, 12 and 24 months mortality for ΔMELD, initial MELD and CP score was compared by c-statistics. Patient survival was also compared at 6, 12 and 24 months according to the cut off values of ΔMELD/month, initial MELD and CP score. Results: Increased MELD score was associated with biochemical and clinical parameters such as esophageal variceal bleeding and onset of hepatic encephalopathy. The area under receiver operating characteristic (ROC) curve for ΔMELD/month was 0.928 (P<0.001) compared with 0.575 for MELD score and 0.636 for CP score at 6 month-mortality; the area was 0.727, 0.594 and 0.657 at 12 month-mortality; 0.693, 0.587 and 0.639 at 24 month-mortality, respectively. The patients with ΔMELD/month more than 1.0 had resulted in the higher mortality at 6, 12 and 24 months. The ΔMELD/month was associated with mortality and was an independent prognostic predictor with a risk ratio of 1.679 (95% CI: 1.381-2.042, P<0.001). Conclusions: Determination of ΔMELD could be better prognostic predictor for patients with liver cirrhosis than initial MELD and CP score. (Korean J Hepatol 2006;12:530-538)

Interequipment Variability of Doppler Ultrasonographic Indices in Patients with Liver Cirrhosis
Backgrounds/Aims: Doppler ultrasongraphy is used to evaluate hemodynamic alternations in patients with liver cirrhosis. Purpose of this study was to determine the interequipment variability of Doppler indices in portal and splenic vein in cirrhosis. Methods: Blood velocity, diameter, flow and congestive index in portal and splenic vein were measured by Doppler ultrasonography in 30 patients with cirrhosis using two different machines. Results: Portal venous velocities measured by HDI-5000 and SSD-5000 were 8.72±3.69 cm/sec, 12.21±2.84 cm/sec, respectively which showed significant difference (P<0.001). Measured portal blood flows and congestive indices also had significant difference between HDI-5000 and SSD-5000 (P<0.01). Splenic venous velocity by HDI-5000 was 8.55±2.71 cm/sec, which was lower than that of 12.32±3.11 cm/sec by SSD- 5000 (P<0.001). Splenic blood flows measured by HDI-5000 and SSD-5000 were 390.73±260.98 mL/min, 595.01±346.53 mL/min, respectively, showing significant difference (P=0.015). However, no differences were in the diameters of portal and splenic vein between HDI-5000 and SSD-5000. Conclusion: Doppler indices in portal and splenic vein showed significant interequipment variability. Therefore, in liver cirrhosis, hemodynamic investigations using different Doppler ultrasonographic machines is inappropriate. (Korean J Hepatol 2006;12:539-545)

Diagnostic Accuracy of 18F-FDG Positron Emission Tomography for Evaluation of Hepatocellular ...
Background/Aims: Positron emission tomography (PET) is an imaging technique reflecting cellular metabolism. However, the feasibility of PET in the diagnosis of hepatocellular carcinoma (HCC) is limited because of vague accuracy and high cost. The aim of this study was to evaluate the diagnostic accuracy of ¹⁸F-FDG-PET in detection of HCC. Methods: We retrospectively studied HCC patients who underwent ¹⁸F- FDG-PET between June 2001 and February 2005 in Korea National Cancer Center. Thirty-two patients were enrolled and HCC status of these patients were verified by surgical pathology or clinical course using imaging studies (CT, MRI or angiography) within 3 months after PET. PET studies were read by 2 specialists for nuclear medicine and determined as malignant when its standardized uptake value (SUV) was over 2.5. Results: HCC was suspected in 21 out of 32 cases on ¹⁸F-FDG-PET. On follow-up, 2 of 21 cases were determined false-positive. In cases of 11 patients without evidence of HCC on ¹⁸F-FDG-PET, 10 patients were found to have HCC on follow-up. Thus, the sensitivity and specificity of ¹⁸F-FDG-PET were 65.5% and 33.3% respectively. The positive predictive value was 90.5%. The diagnostic accuracy was 62.5%. Conclusion: ¹⁸F- FDG-PET showed a low accuracy in diagnosis of HCC. Therefore, ¹⁸F-FDG-PET has a limited role in a staging and detection of occult HCC. (Korean J Hepatol 2006;12:546-552)

The Adverse Effect of Indirectly Diagnosed Portal Hypertension on the Complications and ...
Backgrounds/Aims: Surgical resection is considered as a curative treatment modality for patient with hepatocellular carcinoma (HCC). Since HCC often occurs in chronic liver disease, selecting optimal candidates based on the hepatic function reserve and the risk of hepatic decompensation after resection is important. In recent studies, clinically relevant portal hypertension including hepatic venous pressure gradient (HVPG) is considered as the best predictor of postoperative hepatic decompensation. However, since measuring HVPG requires an invasive procedure it is not widely used in practice. We aimed to evaluate whether the portal hypertension diagnosed indirectly could be a useful parameter for predicting postoperative prognosis. Methods: A total of 142 patients with HCC who had endoscopic examination, computed tomography and surgical resection from January 2001 to June 2004 were included in the study. We diagnosed portal hypertension indirectly by the presence of varices or splenomegaly with thrmobocytopenia. Postoperative complications and survival rate according to the presence of portal hypertension was studied. Results: The postoperative morbidity rate was 42.2%. The incidence of ascites and prolonged hyperbilirubinemia were significantly higher in portal hypertension group (ascites 43.8 vs. 10.3%, hyperbilirubinemia 20.3 vs. 1.3%, respectively, P<0.01). The cumulative 3-year recurrence-free survival rate showed no statistical difference between the two groups. However, the cumulative 3-year survival rate was significantly higher in the non-portal hypertension group (82.8% vs. 53%, respectively, P=0.014). Conclusion: Indirectly diagnosed portal hypertension is correlated with the development of complications and poor prognosis after the surgical resection of HCC. (Korean J Hepatol 2006;12:553-561)

Liver Metastasis of Colon Cancer with a High Serum alpha-Fetoprotein Level: Report of a Case
We report herein a case of 72-year-old woman in whom liver metastasis of colon cancer was presented with a marked elevation of serum alpha-fetoprotein (AFP) level. She was transferred to our hospital for multiple liver masses found on ultrasonogram. Abdominal computed tomogram revealed multiple low-density masses in the liver and wall thickening of the hepatic flexure of colon. The serum AFP level was 10,718.8 ng/mL. Colonoscopic findings of ulcerofungating mass suggested liver metastasis from colon cancer. However, the possibility of combined hepatocellular carcinoma could not be ruled out due to serum AFP elevation. Both colon and liver biopsies revealed moderately differentiated tubular adenocarcinoma. Using an immunohistochemical staining, the adenocarcinoma in liver showed focal positive to AFP, but not in colon. This case represents a very rare case of colon cancer with a marked elevation of serum AFP. (Korean J Hepatol 2006;12:562-567)

A Case of Cavernoma of Portal Vein associated with Polycythemia Vera
Cavernoma of the portal vein is defined as a formation of venous channels within or around a previously thrombosed portal vein. We experienced a 50-year-old woman who presented a huge hepatic mass with right upper quadrant dull pain. Abdominal computed tomography showed a huge sponge-like hepatic mass with cavernous transformation of portal vein along the common bile duct and common hepatic duct. She had increased hemoglobin/hematocrit (15.7 g/dL/49.1%) and red blood cell mass (35 mL/kg). Platelet count was 450,000/?L and white blood cell count was 13,500/?L. Erythropoietin level was low normal range (10.2 mU/ mL). Bone marrow biopsy showed a moderately hypercellular marrow and overall cellularity was about 80- 90%. Megakaryocytes were slightly increased in number with abnormal clusterings Myelopoiesis and erythropoiesis were also slightly increased with moderate to severe fibrosis. She was diagnosed as polycythemia vera with cavernous transformation of portal vein. Repeated thrombosis occurred in the leg and the toe and was treated with angioplasty and thrombolytic therapy with phlebotomy. (Korean J Hepatol 2006;12:568-573)

Drug Induced Hepatitis Mimicking Alcoholic Hepatitis

Dae-Young Kang, M.D. and So-Young Jin, M.D.1

Inflammatory Pseudotumor of the Liver

Joon Koo Han , Se Hyung Kim

The Korean Journal of Serum Hepatitis B Virus DHA Level and Hepatocellulor Carcinoma

Seong Gyu Hwang

2006 AASLD Topics : Topics Related to Hepatitis B

Jong Ryul Eun, M.D.1 and Soo Hyung Ryu, M.D.

2006 AASLD Topics : Topics Related to Hepatitis C

Yeon Seok Seo , Kwang Hee Youn

2006 AASLD Topics : Topics Related to Alcoholic and Nonalcoholic Fatty Liver Disease

Hyun Woong Lee — Sat, 01 Jan 2000 00:00:01 +0100

2006 AASLD Topics : Topic Related to Autoimmune Hepatitis and Hereditary Liver Disease

Yong Sung Choi

2006 AASLD Topics : Topics Related to Liver Fibrogenesis and Cirrhosis

Ja Kyung Kim , Young Joon Yoon

2006 AASLD Topics : Topics Related to Liver Cancer

Byoung Kuk Jang , Woo Jin Chung

2006 AASLD Topics : Topics Related to Liver Transplantation

Young Suk Lim

Design and Conduct of Randomized Controlled Trials (RCTs)

Dong Hun Park , Soon Koo Baik — Sat, 01 Jan 2000 00:00:01 +0100

PIVKA-II as a Serological Marker of Hepatocellular Carcinoma

Sook-Hyang Jeong — Sat, 01 Jan 2000 00:00:01 +0100

Autoimmune Hepatitis: Recent Update on Diagnosis and Treatment

Yung Sang Lee — Sat, 01 Jan 2000 00:00:01 +0100
Autoimmune hepatitis (AIH) is an unresolving, predominantly periportal hepatitis that is usually displays hypergammaglobulinemia, and tissue autoantibodies, and this malady is responsive to immunosuppressive therapy. Our understanding about this clinical entity has been greatly expanded since the first description by Waldenstr?m 50 years ago. The codified diagnostic criteria of AIH prepared by International Autoimmune Hepatitis Group are still valid, but new attempts are being made to overcome the shortcomings of this scoring system. Immunosuppressive therapies using prednisone and azathioprine are currently the mainstay for the treatment of AIH, but there are still many practical questions to be solved.

Wilson Disease: an Update

Jeong Kee Seo — Sat, 01 Jan 2000 00:00:01 +0100
Wilson disease (WD) is an autosomal recessive disorder of copper transport that results in accumulation of copper primarily in the liver, the brain and the cornea. WD is the most common inherited liver disease with the prevalence of 1: 37,000 in the pediatric population in Korea. Mutations in the ATP7B gene cause failure of copper excretion into the bile and a defective incorporation of copper into ceruloplasmin. More than 300 mutations in the ATP7B gene have been described so far. Mutations differ between ethnic groups. The p.R778L (an allele frequency of 37%), p.A874V (13%), p.L1083F (8%) and p.N1270S (6%) are the common major mutations in Korea. Conflicting results on genotype/phenotype correlations of the most common mutations have been reported in various countries. There seems to be no correlation between the R778L mutation and age of onset or clinical manifestations in Korean patients. None of the laboratory parameters alone allows a definite diagnosis of WD. In a nation-wide survey of WD, low serum ceruloplasmin (<20 mg/dL), high 24 hour urine copper (>100 μg), high hepatic copper content (>250 μg/g of dry liver) and Kayser-Fleischer rings were found in 96%, 86%, 88%, and 73% of the 550 Korean patients respectively. A combination of any two of the above 4 laboratory findings is strong support for a diagnosis of WD. For the last couple of years, genetic testing has been playing an increasingly important role in diagnosing WD. Direct DNA sequencing did confirm WD in 98% of the Korean patients. Two mutations were detected in 70% and one mutation in 28% of the patients who showed characteristic biochemical and clinical findings of WD. Genetic testing, either by haplotype analysis or by mutation analysis, is the only reliable tool for differentiating heterozygote carriers from affected asymptomatic patients. The agents of the first choice among chelators and zinc in specific clinical situations of WD is still a matter of debate. Because of frequent side effects and initial neurologic deterioration of penicillamine therapy, less toxic trientine or zinc has gradually replaced penicillamine over the past few years. Trientine or tetrathiomolybdate has been increasingly recommended as the first-line treatment for neurologic WD. Currently, liver transplantation is not recommended as primary treatment for neurologic WD. Recently published data show that initial zinc therapy for asymptomatic/presymptomatic patients and maintenance zinc therapy in patients after long term chelation are safe and effective. Further researches and the new guidelines on the proper management of patients with WD are needed.

Primary Biliary Cirrhosis

Chae Yoon Chon , Jun Yong Park — Sat, 01 Jan 2000 00:00:01 +0100
Primary biliary cirrhosis (PBC) is a chronic cholestatic autoimmune liver disease that predominantly affects middle-aged women. It is characterized by slowly progressive destruction of the small intrahepatic bile ducts together with portal inflammation, and this initially leads to fibrosis and later to cirrhosis. It is currently accepted that the pathogenesis of PBC is multifactorial with genetic and environmental factors interplaying to determine the disease onset and progression. In addition to antimitochondrial antibody (AMA), which is the hallmark of PBC and is detected in at least 90% of the patients, other autoantibodies (antinuclear antibody, anti-smooth muscle antibody and rheumatoid factor, etc.) may also be found in the patients. There is no correlation between the titer of AMAs and the disease severity. Most patients are diagnosed either during the asymptomatic phase of PBC or after presenting with non-specific symptoms. Pruritus and fatigue are the most common symptoms of PBC. The prognosis of PBC has improved significantly during the last few decades. Patients are now diagnosed earlier in its clinical course, they are more likely to be asymptomatic at diagnosis and they are more likely to receive medical treatment. A wide variety of drugs have been assessed for the treatment of this condition: such immunosuppressive agents as corticosteroids, cyclosporine and azathioprine have a weak effect on the disease’s natural history. Ursodeoxycholic acid (UDCA) is the only currently approved medical treatment. For PBC patients with end-stage liver disease or an unacceptable quality of life, liver transplantation is the only accepted therapeutic option. Early diagnosis and treatment of PBC are important because effective treatment with UDCA has been shown to delay disease progression and improve rate survival in the early stage.

A Prospective Study Comparing the Efficacy of Early Administration of Terlipressin and ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Terlipressin and somatostatin decrease portal venous pressure and they are used for the treatment of variceal bleeding. However, only a few studies have compared the efficacy of these drugs in combination with other procedures for hemostasis. Therefore, we performed a prospective study to compare the efficacy of terlipressin and somatostatin for controlling acute variceal bleeding when used in combination with other procedures for hemostasis. Methods: A total of 98 patients, who presented with variceal bleeding from September 2003 to May 2005, were randomly divided into the somatostatin group or terlipressin group. We compared the 5-day failure rate (defined as failure to control bleeding, rebleeding or death within 5 days of admission) and the 6-week mortality. The prognostic factors for 5-day failure and 6-week mortality were also evaluated. Results: There were no differences in baseline characteristics between the two groups. The overall 5-day failure rate and the cumulative 6-week mortality were 16.3% and 15.8%, respectively. The five-day failure rate and the cumulative 6-week mortality were not significantly different between the somatostatin and terlipressin groups. Hepatocellular carcinoma, the baseline serum creatinine level and endoscopic treatment for hemostasis were the significant predictors of 5-day failure; the baseline serum creatinine level was the predictor of 6-week mortality. Conclusions: Both somatostatin and terlipressin were effective and showed comparable efficacy for the control of the acute variceal bleeding in the setting of a combined therapeutic approach. The baseline serum creatinine level may be a significant predictor for patient failure at 5 days and the 6-week mortality.

Comparison of Terlipressin and Octreotide with Variceal Ligation for Controlling Acute ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Terlipressin and octreotide had been used to control acute variceal bleeding and to prevent early rebleeding after endoscopic hemostasis. We compared the efficacy and safety of terlipressin and octreotide combined with endoscopic variceal ligation (EVL) for the treatment of acute esophageal variceal bleeding and we evaluated their clinical significance as related to rebleeding. Methods: The eighty eight cirrhotic patients were randomized to the terlipressin group (n=43; 2 mg i.v. initially and 1 mg i.v. at every 4 hours for 3 days) or the octreotide group (n=45; continuous infusion of 25 μg/h for 5 days) combined with EVL for the treatment of acute esophageal variceal bleeding. Results: The initial hemostasis rates were 98% (42/43 cases) in the terlipressin group and 96% (43/45 cases) in the octreotide group. The 5-day and 42-day rebleeding rates were 12% (5/43 cases) and 28% (12/43 cases), respectively, in the terlipressin group and 9% (4/45 cases) and 24% (11/45 cases), respectively, in the octreotide group. No significant difference was demonstrated between the terlipressin and octreotide groups. The mortality at 42 days was similar in both group, but a high mortality rate (48%) was shown to be related to 42-day rebleeding. The risk factors related to 42-day rebleeding were Child-Pugh class C (aOR=30.2, 95% CI=7.7-117.9), ascites above grade II (aOR=6.6, 95% CI=2.2-19.2) and advanced hepatocellular carcinoma (aOR=4.6, 95% CI=1.1-18.9). Conclusions: Comparing terlipressin and octreotide combined with EVL showed them to be equally safe and effective therapeutic agents in patients with acute esophageal variceal bleeding. The high risk factors related to early rebleeding were poor liver function and advanced hepatocellular carcinoma.

Effect of Endoscopic Sclerotherapy Using N-butyl-2-cyanoacrylate in Patients with Gastric ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Gastric variceal bleeding is a severe complication of cirrhosis, and it has a high mortality rate. This study was conducted to evaluate the efficacy of n-butyl-2-cyanoacrylate injection therapy for patients suffering with gastric variceal bleeding. Methods: A total of 86 patients diagnosed with gastric variceal bleeding underwent endoscopic n-butyl-2-cyanoacrylate (HistoacrylⓇ) injection therapy at our department between April, 2002 and July, 2005, with a mean follow-up period of 44 weeks (range: 2 to 136 weeks). The initial hemostasis rate and the rebleeding rate of endoscopic sclerotherapy were analyzed. Also, the cumulative survival rate was analyzed according to the status of hepatocellular carcinoma and hyponatremia, the MELD score, the Child-Pugh score and the amount of injected HistoacrylⓇ. Results: The initial hemostasis rate of HistoacrylⓇ injection therapy was 93% and the 1 month rebleeding rate was 16.1%. The total number of session for treating the initial hemostasis was 1.2±0.4 and the total volume of HistoacrylⓇ was 2.7±1.2 mL. The cumulative rebleeding-free rates for the patients treated by the HistoacrylⓇ injection method at 1 month, 12 months and 34 months period were 95.1%, 83.2% and 74%, respectively. The cumulative survival rates were 78.3% at 1 month, 61.9% at 12 months and 54.6% at 34 months, respectively. No thromboembolic phenomenon occurred. According to the Cox’s proportional hazards analysis, only the MELD score (<15) was an independent predicting factor for survival of the patients with gastric variceal bleeding. Conclusions: Endoscopic sclerotherapy using n-butyl-2-cyanoacrylate was a safe and effective hemostatic method for patients with gastric variceal bleeding. Also, the MELD score (<15) contributed to predicting survival of the patients with gastric variceal bleeding.

Optimal Cut-off Value of PIVKA-II for Diagnosis of Hepatocellular Carcinoma - Using ROC Curve -

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Protein induced by vitamin K absence or antagonist-II (PIVKA-II), also known as des-carboxyprothrombin (DCP), can be used as an alternative tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma (HCC). The aims of the present study were to compare PIVKA- II levels between the patients with HCC and patients with non-HCC chronic liver disease, to evaluate the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the receiver operating characteristic (ROC) curve. Methods: A total of 227 consecutive patients with HCC (n=42) or chronic liver disease (n=185) were enrolled in this study. HCC was diagnosed histologically or by imaging such as computed tomography, magnetic resonance imaging or angiography. The serum PIVKA-II and AFP levels were measured by electrochemiluminoimmunoassay with using the Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. Results: The PIVKA-II level in the HCC patients was significantly higher than the non-HCC chronic liver disease patients (903.0±1156.7 vs. 111.7±211.0 mAU/ mL, respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%. Conclusions: PIVKA-II was as useful surveillance tool for differentiating HCC from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a significant cut-off value for diagnosis of hepatocellular carcinoma.

Surgical Treatment of Sclerosing Hepatocellular Carcinoma

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Sclerosing hepatocellular carcinoma (HCC) is an unusual subtype of HCC that is characterized by an embedded dense fibrous stroma in the tubular neoplastic structures. We aimed to assess the surgical approaches and outcomes of sclerosing HCC. Methods: We retrospectively analyzed the clinicopathologic features of 6 patients with sclerosing HCC who underwent surgical treatment at Asan Medical Center between July 1989 and December 2005. Results: Six HCC patients with sclerosing HCC were diagnosed out of the total 1390 HCC patients (0.43%) during the study period. The mean age was 58 years and 4 patients were male. Weight loss and abdominal pain were the most common symptoms. The serum calcium and phosphorus levels were normal in all the patients. All of them were hepatitis B surface antigen-positive, but none was positive for hepatitis C. All the lesions were solitary. The tumor size ranged from 45 to 150 mm in diameter (median size: 81 mm). We performed right trisegmentectomy (n=1), central bisegmentectomy (n=1), right anterior segmentectomy (n=1), ex-vivo resection and autotransplantation (n=1) and right posterior segmentectomy (n=2). The median overall survival and disease free-survival periods were 24 months and 9.5 months, respectively. Conclusions: The incidence of sclerosing HCC was very low. Sclerosing HCC was often not correctly diagnosed before an operation, but performing resection prolonged the patients’ survival and their prognosis was not worse than that for ordinary HCC. Our experience implicates that aggressive surgical treatment for sclerosing HCC is beneficial for patient survival. (Korean J Hepatol 2006;12:412-419)

Reappraisal of Risk Factors Predicting Liver Complications from Radiotherapy for Hepatocellular ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Determination of the optimal radiotherapeutic parameters for radiotherapy of hepatocellular carcinoma (HCC) is still under investigation. The purpose of this study is to identify the risk factors associated with radiation-related morbidity. Methods: We evaluated one hundred fifty-eight patients, who were given radiotherapy for HCC between January 1992 and March 2000. Radiation-induced liver disease (RILD) was defined as the development of nonmalignant ascites without disease progression and an anicteric elevation of the alkaline phosphatase level by at least twofold. Gastrointestinal toxicity was assessed by using the RTOG-EORTC scale. Results: Six patients (3.8%) displayed RILD. In these patients, three patients had not responded to other previous treatments. Two patients with portal vein thrombosis or huge sized mass, above 10 cm, showed liver toxicity and two other patients presented with Child-Pugh class B liver cirrhosis. Eight patients (5%) had gastro-duodenal ulcers. In one of these 8 patients, the left lobe close to the stomach was involved and two patients had been treated for gastro-duodenal ulcer. In two more patients, the radiation field, with using anterior/posterior radiation ports, covered a significant volume of the gastrointestinal tract. One of eight patients had been irradiated with a large fraction size (250 cGy). Conclusions: The efforts should be made to reduce the radiation-related complications for hepatocellular carcinoma by considering the volume and the function of remaining liver, the location of tumor, the tumor size and the severity of liver cirrhosis

Inflammatory Pseudotumor of Liver- A Clinical Review of 15 Cases -

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Inflammatory pseudotumor rarely occurs in the liver. However, it is important to discriminate it from malignant hepatic tumor in order to avoid unnecessary surgery. We aimed to elucidate the characteristic features of this disease entity by analyzing our experiences and by reviewing the related literatures. Methods: Fifteen patients were enrolled during a recent three-year period. The patients were pathologically diagnosed with inflammatory pseudotumor of the liver, and their clinical and imaging findings were analyzed retrospectively. Results: Our study population was composed of ten men and five women, and their mean age was 60.3±9.2 years. Their initial diagnoses were inflammatory pseudotumor (n=8), malignant tumors (n=3) and abscess (n=4). Twelve of 15 patients were associated with biliary diseases such as biliary stone, gallbladder cancer, empyema or cholangiocarcinoma. The most common symptom was abdominal pain. The most common CT and MR findings could be summarized as a delayed hyperattenuating mass with an internal hypoattenuating component. The tumors were solitary in 13 patients and multiple in two patients. The lesions regressed spontaneously in seven patients. Four patients were treated by antibiotics and 3 patients by surgical resection. Conclusions: Inflammatory pseudotumor of the liver seems to have relatively common clinical and imaging features, as described above. However, these features are not disease-specific; thus, preoperative histologic confirmation is necessary to avoid unnecessary surgery.

A Case of Needle Tract Implantation of Hepatocellular Carcinoma after Percutaneous Biopsy with ...

Samuel Chang , Hyo Keun Lim — Sat, 01 Jan 2000 00:00:01 +0100
Needle tract implantation of hepatocellular carcinoma (HCC) is a rare complication of percutaneous biopsy, and it is largely associated with end-cutting needles or aspiration biopsy. The CT findings that have been reported include oval or round soft tissue nodules with persistent contrast enhancement along the needle tract, mostly in the subcutaneous tissue or the intercostal muscle layers. In this report, we describe a case of needle tract implantation of HCC after US-guided percutaneous biopsy with an 18G tru-cut needle. (Korean J Hepatol 2006;12:439-443)

A Case of Bell`s Palsy Associated with Peginterferon Alfa-2a and Ribavirin Therapy for Chronic ...

Moo Yeol Lee, M.D., Hoon Cho, M.D., Yeong Muk Kim, M.D., and Joon Sang Lee, M.D. — Sat, 01 Jan 2000 00:00:01 +0100
Pegylated interferon alfa-2a (PEG-IFN) and ribavirin combination therapy is the first line treatment for chronic HCV infection. There are four reports of Bell’s palsy associated with interferon-α (IFN-α) and ribavirin therapy. We report here a case of Bell’s palsy that occurred in a patient with chronic HCV infection during combination PEG-IFN and ribavirin therapy. The patient was 49-year-old man with chronic hepatitis C for 2 years. The liver biopsy showed grade 1 and stage 1. Therapy with PEG-IFN (Pegasys) 180 μg/week and ribavirin 1200 mg/day was initiated. After 3 weeks of treatment, the patient showed a loss of muscular tone on the left side of his face. A diagnosis of Bell’s palsy was made, and the PEG-IFN and ribavirin therapy was stopped. Prednisolone 45 mg/d was given and then tapered for 8 weeks. His palsy improved over 6 weeks. (Korean J Hepatol 2006;12:444-448)

A Case of Complete Regression of Hepatocellular Carcinoma during Administration of COX-2 Inhibitor

Sat, 01 Jan 2000 00:00:01 +0100
Overexpression of cyclooxygenase-2 (COX-2) has been associated with hepatocarcinogenesis. Inhibitors of COX-2 have proapoptotic and antiproliferative effects on malignant tumors and inhibit tumor invasion to the surrounding tissues. We report here a case of complete regression of advanced hepatocellular carcinoma (HCC) during COX-2 inhibitor administration. An eighty-year-old female was diagnosed as an advanced HCC, which was associated with HCV infection. She received COX-2 inhibitor for 3 months due to degenerative arthritis of both knees. Tumor enhancement on arterial phase CT completely disappeared without specific treatment for the HCC, and the tumor size decreased on the follow-up CT scan. (Korean J Hepatol 2006; 12:449-454)

Nonalcoholic Steatohepatitis

So-Young Jin — Sat, 01 Jan 2000 00:00:01 +0100

Focal Peliosis Hepatis Mimicking Hepatocellular Carcinoma

Joon Koo Han , Se Hyung Kim — Sat, 01 Jan 2000 00:00:01 +0100

The Korean Journal of Prevention of Variceal Bleeding and Measurement of Hepatic Vein Pressure ...

Kwang Hee Youn , Dong Joon Kim — Sat, 01 Jan 2000 00:00:01 +0100
Objectives: A reduction in hepatic venous pressure gradient (HVPG) of ≥20% of baseline or to ≤12 mmHg (responders) is associated with a reduced risk of first variceal bleeding. The aim of this study was to evaluate whether this protective effect is maintained in the long term and if it extends to other portal hypertension complications. Methods: Seventyone cirrhotic patients with esophageal varices and without previous variceal bleeding who entered into a program of prophylactic pharmacological therapy and were followed for up to 8 yr were evaluated. All had two separate HVPG measurements, at baseline and after pharmacological therapy with propranolol± isosorbide mononitrate. Results: Forty-six patients were nonresponders and 25 were responders. Eightyear cumulative probability of being free of first variceal bleeding was higher in responders than in nonresponders (90% vs 45%, p=0.026). The lack of hemodynamic response and low platelet count were the only independent predictors of first variceal bleeding. Additionally, reduction of HVPG was independently associated with a decreased risk of spontaneous bacterial peritonitis (SBP) or bacteremia. No significant differences in the development of ascites, hepatic encephalopathy, or survival were observed. Conclusions: The hemodynamic response in cirrhotic patients is associated with a sustained reduction in the risk of first variceal bleeding over a long-term follow-up. Reduction of HVPG also correlate with a reduced risk of SBP or bacteremia. [Abstract reproduced by permisson of Am J Gastroenterol 2006;101:506-512]

Colorectal Cancer in Inflammatory Bowel Disease

Jonathan Potack , Steven H. Itzkowitz — Thu, 01 Jan 1970 09:00:00 +0100
Patients with long-standing inflammatory bowel disease have an increased risk of developing colorectal cancer (CRC). CRC risk increases with longer duration of colitis, greater anatomic extent of colitis, the presence of primary sclerosing cholangitis, family history of CRC and severity of inflammation of the colon. Chemoprevention includes aminosalicylates, ursodeoxycholic acid, and possibly folic acid. To reduce CRC mortality in IBD, colonoscopic surveillance remains the major way to detect early mucosal dysplasia. When dysplasia is confirmed, proctocolectomy is considered for these patients. Ulcerative colitis patients with total proctocolectomy and ileal pouch anal-anastomosis have a rather low risk of dysplasia in the ileal pouch, but the anal transition zone should be monitored periodically. New endoscopic and molecular screening approaches may further refine our current surveillance guidelines and our understanding of the natural history of dysplasia.

Cerulein Pancreatitis: Oxidative Stress, Inflammation, and Apoptosis

Hye Young Kim — Thu, 01 Jan 1970 09:00:00 +0100
Cerulein pancreatitis is similar to human edematous pancreatitis, manifesting with dysregulation of digestive enzyme production and cytoplasmic vacuolization, the death of acinar cells, edema formation, and infiltration of inflammatory cells into the pancreas. Reactive oxygen species are involved in nuclear factor-κB activation, cytokine expression, apoptosis and pathogenesis of pancreatitis. There is recent evidence that cerulein activates NADPH oxidase, which is a major source of reactive oxygen species during inflammation and apoptosis in pancreatic acinar cells. In addition, the Janus kinase/signal transducer and activator of transcription pathway has been suggested as being involved in inflammatory signaling in the pancreas. This review discusses the involvement of oxidative stress in inflammation and apoptosis in pancreatic acinar cells stimulated with cerulein as an in vitro model of pancreatitis.

Conference Report: Korea-Japan Symposium on Autoimmune Pancreatitis

Thu, 01 Jan 1970 09:00:00 +0100
A consensus meeting on autoimmune pancreatitis (AIP) was held in Seoul on August 31, 2007. Many Korean and Japanese gastroenterologist interested in AIP participated in the joint symposium, and issues related to histology, radiology, clinical manifestation, serology, and diagnostic criteria were discussed. This joint meeting indicated the need for unified diagnostic criterion for AIP in Korea and Japan. Here, we provide a summary of the symposium presentations and discussions.

Management Strategies for Gallbladder Polyps: Is It Possible to Predict Malignant Gallbladder ...

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: Gallbladder (GB) polyps are commonly encountered in clinical practice, and are found more frequently as the number of medical screening examinations increases. The aim of this study was to determine optimal practice guideline for surgical treatment and follow-up of GB polyps. Methods: Data from healthy subjects of Seoul National University Hospital (SNUH) Health Care System of Gangnam Center were used to investigate the true prevalence of GB polyps. We also enrolled 689 patients with GB polyps diagnosed at SNUH from May 1st, 1988 to April 30th, 2006. Results: The GB polyp prevalence was 6.1% (7.1% in males and 4.8% in females). The median follow-up duration in the 689 study patients was 60 months, and 139 (20%) of them had polyps ≥10 mm in size. Twenty-five of the 180 patients who underwent cholecystectomy had adenocarcinomas. The X2 test was used to identify which of the following were risk factors of malignancy: age, sex, symptoms, size, rate of growth, multiplicity, accompanying stones, and shape. Age (≥57 years), presence of symptoms, size (≥10 mm), and shape (sessile) were found to be statistically significant risk factors by univariate analysis. However, multivariate analysis identified only age (≥57 years) and size (≥10 mm) as independent predictors of malignancy. Conclusions: The present study shows that GB polyps ≥10 mm in size in patients aged ≥57 years are the independent factors predicting malignancy of the GB.

Submucosal Injection of Normal Saline can Prevent Unexpected Deep Thermal Injury of Argon ...

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: There have been several reports of thermal injury induced by argon plasma coagulation (APC) in animal models, but no follow-up studies have revealed the actual thermal injury. Methods: APC was performed on the stomachs of two living minipigs with and without prior submucosal injection of normal saline. The power and argon gas flow were set to 60 watts and 2 L/min, respectively, and pulse durations of 5, 10, and 20 seconds were used. One of the minipigs was killed immediately thereafter and the other was killed 1 week later. Results: The minipig killed immediately showed only subtle differences between noninjected and injected injuries under all the conditions, and the usefulness of prior submucosal injection was not obvious. However, the minipig killed 1 week later had a deep ulcer extending to the deeper muscle layer at the noninjected site where APC had been applied for 20 seconds, whereas tissue injury of the injected site was limited to the submucosal layer. Conclusions: Unexpected tissue damage can occur even using a short-duration APC. Prior submucosal injection for APC might be a safer alternative technique, especially in a thinner and narrower gut wall.

Effect of Low-dose, Enteric Coated Aspirin on Gastrointestinal Bleeding in Patients with ...

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: This study was performed to determine whether low-dose aspirin and/or clopidogrel can induce gastrointestinal bleeding and gastroduodenal mucosal injury. Methods: A total of 387 patients who underwent coronary angiography at Seoul National University Bundang Hospital were assigned to one of three antiplatelet treatment groups: (1) control, (2) 100-mg enteric coated aspirin, and (3) 100-mg enteric coated aspirin plus clopidogrel. The incidences of gastroduodenal mucosal injury and gastrointestinal bleeding were prospectively evaluated, and risk factors for gastrointestinal bleeding were analyzed. Results: The rate of gastroduodenal mucosal injury was higher in the aspirin-plus-clopidogrel group than in the aspirin group (p=0.012), and higher in the aspirin group than in the control group (p=0.049). The rate of gastrointestinal bleeding was significantly higher in the aspirin-plus-clopidogrel group (9.4%) than in the control group (2.4%, p=0.048). The risk factors for gastrointestinal bleeding were older age (≥60 years) and the presence of at least two comorbid disorders. Conclusions: Low-dose enteric coated aspirin was found to be safe in patients with coronary artery disease, but the addition of clopidogrel increased the rate of gastrointestinal bleeding. Combined clopidogrel and aspirin should be used with caution in older patients having at least two comorbid conditions.

Endoscopic Sedation in Developing and Developed Countries

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: Data are scarce on endoscopic sedation practices outside the United States and Western Europe, particularly from developing nations. An Internet survey was used to assess endoscopic sedation practices in developing and developed countries. Methods: Responses to a Web-based survey of sedation practices from 165 expert endoscopists from 81 countries were analyzed. The most common sedation method was defined as that used for ＞50% of endoscopies within a country. Results: Responses were received from 84 endoscopists practicing in 46 countries (51% response rate; 32 responses from 22 developing countries and 52 responses from 24 developed countries). A combination of benzodiazepine and opioid was the most common method for esophagogastroduodenoscopy (EGD) in 40% of the countries and for colonoscopy in 56% of the countries. For propofol and unsedated endoscopy, the corresponding figures were 8% and 19% for EGD and 18% and 10% for colonoscopy. No single sedation method accounted for ＞50% of EGD and colonoscopy cases in 32% and 17% of the countries, respectively. There were no significant differences in the proportions of developing and developed countries using combined benzodiazepine and opioid, propofol, or unsedated endoscopy. Conclusions: Sedation is used for most endoscopic procedures worldwide, with sedation practice not differing significantly between developing and developed countries.

Volatile Sulfur Compounds as a Predictor for Esophagogastroduodenal Mucosal Injury

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: Halitosis is a symptom that bothers patients more socially than medically and its pathogenic mechanisms are unclear and treatment armamenterium is limited. Clinicians generally ignored active interventions. Since halitosis is closely associated with volatile sulfur compounds (VSCs), we used a Halimeter and gas chromatography to measure VSCs in patients with Helicobacter-pylori (H. pylori)- associated gastric diseases. Methods: We categorized 72 patients with H. pylori infection into two groups based on their endoscopic findings: a nonerosive mucosal group (NE, n=24) and an erosive mucosal group (E, n=48). Halitosis was objectively assessed by applying either a Halimeter to breath air or gas chromatography to gastric juice. Simultaneously, the expression of VSC-generating enzyme was measured with reverse-transcriptase PCR using mRNA isolated from biopsy tissues. Results: The levels of VSCs in exhaled breaths or aspirated gastric juices differed significantly between the NE and E groups (p<0.00001), suggesting that VSCs might reflect eroded epithelial damage induced by H. pylori infection. The expressions of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) were broadly consistent with the degree of mucosal injury. Conclusions: Erosive changes in esophagogastroduodenal mucosa were strongly correlated with increased VSC levels, suggesting that halitosis might result from H. pylori- associated erosive lesions.

Methylation of the Tumor Suppressor Gene RUN

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: RUN×3 (PEBP2αC/CBFA3/AML2) is a novel tumor suppressor gene in the human gastric carcinoma. The aims of this study were to determine the methylation of RUN×3 promoter and the association between RUN×3 methylation and the clinicopathological characteristics of patients with gastric carcinoma. Methods: Seventy-nine patients with gastric carcinoma were studied prospectively from April 2005 to May 2007. The methylations of RUN×3 promoter on the gastric carcinoma specimens and the corresponding nonneoplastic mucosa were evaluated by methylation-specific polymerase chain reaction. Results: Comparison of the results with the clinicopathological characteristics identified RUN×3 monoallelic methylation in 32.9% (26/79) of the gastric carcinoma patients and in 11.4% (9/79) of those with nonneoplastic mucosa (p=0.053). The monoallelic methylated gastric carcinoma specimens predominantly consisted of well- and moderately differentiated carcinomas (44.7%), with the unmethylated group constituting 22.0% of them (p=0.031). Among the 48 patients (60.8%) who underwent gastrectomy, there was no correlation between the two groups with regard to Lauren`s classification (p=0.235), depth of invasion (p=0.990), nodal status (p=0.601), stage (p=0.900), lymphatic invasion (p=0.537), and vascular invasion (p=0.815). Conclusions: Methylation of the tumor suppressor gene RUN×3 might be one of the mechanisms involved in the pathogenesis of gastric carcinoma.

Hematochezia with Colonic Polypoid Angiodysplasia in a Young Female Patient

Thu, 01 Jan 1970 09:00:00 +0100
A 18-year-old girl visited the hospital due to hematochezia. Colonoscopy revealed a 6-mm Yamada type II polyp with stigmata of bleeding, and a shallow ulcer on top was found at the cecum base. The polyp was removed by snare polypectomy, and hematochezia stopped thereafter. Angiodysplasia was diagnosed histopathologically. Generally, angiodysplasia appears as a flat or elevated, bright-red lesion on endoscopy, with a polypoid shape being extremely rare. This case is significant because the lesion occurred at the youngest reported age and was the smallest that has been reported, and is the only polypoid arteriovenous malformation to be discovered in the cecum.

Infarction and Perforation of the Small Intestine due to Tumor Emboli from Disseminated Rectal ...

Thu, 01 Jan 1970 09:00:00 +0100
Small bowel perforation due to hematogenous metastatic tumor emboli is a rare event, especially in a patient with rectal cancer. We report a 75-year-old man with relapsed rectal cancer who developed an acute abdomen, which was found to be due to a perforated terminal ileum. Emergency surgery involved segmental resection and ileostomy. The pathology of the resected small bowel showed multifocal and extensive metastatic tumor emboli in the entire wall, leading to transmural infarction followed by perforation, without a discrete tumor mass. The pathology with immunohistochemistry showed a rectal tumor that was positive for CK-20 but negative for CK-7 and TTF-1. This extremely rare complication of rectal cancer resulted from ischemia and infarct caused by disseminated metastatic tumor emboli without direct invasion or mass formation.

Clinical Significance and Natural History of "HBeAg Negativity" in Patients with ...

Young Sok Lee

Black Esophagus Associated with Alcohol Abuse

Thu, 01 Jan 1970 09:00:00 +0100
Black esophagus is a rare condition of the esophagus that manifests as endoscopic findings of black-colored esophageal mucosa, which is usually caused by acute esophageal necrosis. We report a case of alcoholic patient who developed black esophagus. The 85-yearold man was admitted to Severance Hospital due to copious hematemesis over 2 days. Upper gastrointestinal endoscopy showed black-colored mucosa in the distal esophagus. Endoscopic biopsies of the esophagus revealed necrotic tissue, without any viable cells. Follow-up upper gastrointestinal endoscopy performed after supportive care with a proton-pump inhibitor, sucralfate, and total parenteral nutrition resulted in the remarkable healing of the esophageal wall with no complications.

Prevalence and Clinical Implications of Occult Hepatitis B Virus Infection

Sung Won Cho

Immunology of Hepatitis C: Clinical Significance of T Cell Response

Eui Cheol Shin
Hepatitis C virus (HCV) infection is a worldwide problem in terms of public health. It causes chronic hepatitis C in 60-80% of patients after acute hepatitis C. Chronic hepatitis C can progress to liver cirrhosis and hepatocellular carcinoma. In the present time, combination therapy of pegylated interferon-α and ribavirin is the standard therapy for hepatitis C, but it results in sustained virologic response only in 45-80% of treated patients. In addition, there is no available effective vaccine for HCV. To develop effective immunotherapy or preventive vaccine, understanding of the immune response against HCV is prerequisite. Among several components of immune system, T cells play a key role in the clearance of HCV and immunopathology during hepatitis C. In the study of HCV infection, however, the most important limiting factor is the absence of small animal model as only humans and chimpanzees can be infected by HCV. In this review, T cell response against HCV, which has been known from the studies of the HCV-infected patients and chimpanzees, will be discussed in several circumstances, including acute hepatitis C, chronic hepatitis C and recovered status from hepatitis C. (Korean J Hepatol 2006;12:140-153)

Action Mechanism in Immunopathogenesis and Clearance of HBV

Se Jin Im , Young Chul Sung
Hepatitis B virus (HBV) currently infects more than 400 million people worldwide and they are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. The immune response to HBV- encoded antigens is responsible both for viral clearance and for disease pathogenesis during HBV infection. While the humoral antibody response to viral envelope antigens contributes to the clearance of circulating virus particles, the cellular immune responses to the envelope, nucleocapsid, and polymerase antigens were known to eliminate virus in infected hepatocytes through cytolytic as well as noncytolytic mechanisms. Liver injury could be initiated by an immune response against HBV, but mainly resulted from HBV non-specific lymphocytes and macrophages. There are growing evidences that T helper 1 memory T cells play a predominant role in suppressing viral replication mainly by IFN-γ through noncytolytic antiviral mechanism. Elucidation of the immunological and virological basis for HBV infection may yield effective immunotherapeutic and antiviral strategies to terminate chronic HBV infection. (Korean J Hepatol 2006;12: 154-162)

Natural History of HBeAg Negative Chronic Hepatitis B Virus Infection; A Cohort Study
Background/Aims: The long-term virologic and biochemical changes in patients with HBeAg negative HBV infection, especially in Asia, remain unclear. To address this issue, we conducted a 3 year- retrospective, cohort study. Methods: A total of 157 patients with HBeAg negative HBV infection who were monitored without treatment were reviewed between January 1999 and March 2004. Those patients were followed up every 3 months with liver function tests and serologic tests. All patients were stratified into 3 groups; inactive carrier (IC), viremic carrier (VC) and chronic hepatitis (CH). Serum HBV DNA was measured by a hybridization assay (sensitivity: 1.4×105 genomes/mL, Digene Diagnostics, Silver Spring, USA). Results: The median age of enrolled patients was 42.7 years (M:F=2.3:1). By single time-point observations, the 3 year-cohort prevalence of HBeAg negative CH varied from 12.7 to 35.8% (median 20.7%) HBeAg negative CH was accumulated over time (P=0.002) and transition rates among three groups after 3 years of follow-up are as follows: IC to CH, 6.0%; IC to VC, 4.1%; VC to CH, 23.2%. VC seems to be a disease state in the middle of transition from IC to CH. Conclusions: We demonstrated the dynamic changing patterns of HBeAg negative CH with time, of which the change from IC or VC to CH was dominant. (Korean J Hepatol 2006;12:163-172)

Correlation of HBV DNA Level and Viral Breakthrough During Lamivudine Therapy for Chronic ...
Background/Aims: Lamivudine is an effective therapy in chronic hepatitis B patients, but the emergence of resistant hepatitis B virus (HBV) mutants is a major concern. This study was performed to investigate whether serum viral DNA levels during lamivudine therapy are related with viral breakthrough in patients with chronic HBV infection. Methods: This study consisting of 103 patients was performed retrospectively and prospectively. Follow-up duration was 24 months after lamivudine therapy. Serum HBV DNA levels were quantified by PCR-based assay every 6 months. Results: Cumulative rate of viral breakthrough was 0%, 19.4%, 36%, and 48.5% in 6, 12, 18, and 24 months respectively. The rate of viral breakthrough in 24 months increased as serum HBV DNA levels increased at 6 months. When serum HBV DNA levels were 2-3 log10, 3-4 log10, 4-5 log10, and 5 log10 copies/mL or more, the breakthrough rates were significantly higher than that of the HBV DNA level less than 2 log10 copies/mL. The relative risks were 1.10, 1.93, 2.69, 3.21 respectively (P<0.001). The viral breakthrough rate also increased as serum HBV DNA levels at 12 months increased. When the HBV DNA levels were 2-3 log10, 3-4 log10, 4-5 log10, and 5 log10 copies/ mL or more, the breakthrough rate were significantly higher than those of HBV DNA level less than 2 log10 copies/mL. The relative risks were 2.42, 4.35, 3.73, 2.61, respectively (P=0.002). Conclusions: The serum HBV DNA levels at 6 months and 12 months during lamivudine therapy can be closely correlated with the rate of viral breakthrough in 24 months. (Korean J Hepatol 2006;12:173-183)

Comparison of Clinical Outcome Between Patients Continuing and Discontinuing Lamivudine Therapy ...

Jong Ryul Eun
Backgrounds/Aims: Continuation of lamivudine therapy is controversial for patients with chronic hepatitis B when viral breakthrough occurs. Moreover, the effect of continuous lamivudine therapy is unknown in patients with acute exacerbation after viral breakthrough. We assessed clinical course of acute exacerbation after viral breakthrough in patients who continued and discontinued lamivudine therapy. Methods: Medical records of 109 patients with viral breakthrough during lamivudine therapy were reviewed. Of 40 patients with acute exacerbation (ALT level >5×ULN), adefovir dipivoxil was unavailable in 38 patients. These 38 patients (mean age 42.6 years; male/female, 34/6) were divided into continuation (n=21) and discontinuation (n=17) groups. Clinical courses of the 2 groups were compared. Results: During follow- up period (mean, 27 months; range, 6-60 months), ALT levels decreased to <2×ULN in 11 patients (52%) of continuation group and 9 patients (53%) of discontinuation group, varied from 2× to 5×ULN in 9 (43%) and 5 (29%), respectively, and increased to >5×ULN in 1 (5%) and 3 (18%), respectively, with no statistical significance (P=.417). Conclusions: When acute exacerbation of ALT levels occurs after viral breakthrough during lamivudine administration in patients with compensated chronic hepatitis B, continuation of lamivudine may have no advantage over discontinuation. (Korean J Hepatol 2006;12:184-190)

Change of Hepatitis B Virus DNA Status in Anti-HBc Positive Liver Graft
Background/Aims: Many patients with positive anti-HBc, but negative HBsAg, are known to harbor occult HBV infection, which may transmit the virus through the graft in liver transplantation. We examined the change of HBV DNA within the liver allograft tissue of the donor with positive anti-HBc, but negative HBsAg, before and after the transplantation and assessed its significance. Methods: Twenty-eight patients with available posttransplant biopsies that received anti-HBc positive liver allografts between April 2000 and November 2003 were enrolled in the study. Intraoperative wedge biopsy of donor liver and needle biopsy of the recipient around the 12th postoperative day were used. HBV DNA within the liver tissue was identified by polymerase chain reaction technique using paraffin-embedded liver tissue. Results: Among 13 patients that showed positive amplification before transplantation, 10 turned negative and 3 remained positive after transplantation. One patient, who was negative, became positive after transplantation. Three patients had recurrent HBV infection, but none had positive PCR before or after transplantation and recurrence was not associated with PCR results. Donors with low anti-HBs titer were more likely to be PCR positive compared to donors with high anti-HBs serology (P<0.05). Conclusions: Under adequate prophylactic measures, the presence of HBV DNA within the liver tissue does not affect recurrence and most allografts harboring HBV DNA before transplantation will eventually show viral clearance. However, many anti-HBc positive allografts are infected by HBV at subclinical level so vigilant surveillance is essential. (Korean J Hepatol 2006;12: 191-200)

Detection of Intrahepatic HBV DNA in HBsAg-negative Liver Diseases
Backgrounds/Aims: Occult HBV infection is characterized by the presence of HBV infection with undetectable HBsAg. This study was carried out to find out the frequency of HBV infection in HBsAg- negative patients. Methods: Fifty-six HBsAg-negative patients including 17 anti-HCV positive patients were evaluated. Patients were grouped according to their serological status; group A (anti-HBc+, anti-HBs-, n=16), B (anti-HBc+, anti-HBs+, n=26), and C (anti-HBc-, anti-HBs+/-, n=14). DNA was extracted from frozen liver biopsy specimen, and HBV DNA level was measured with real-time PCR. Results: Overall frequency of detectable intrahepatic HBV DNA was 34% (19/56). The frequency was 56% (9/16) in group A, 31% (8/26) in group B and 14% (2/14) in group C (P=0.01). Intrahepatic HBV DNA levels were as follows; 2,010±6,660 copies/mg in group A, 6,180±29,530 copies/mg in group B and 350±1,220 copies/mg in group C. The frequency of occult HBV infection was not increased in anti-HCV positive patients. Conclusions: Intrahepatic HBV DNA is frequently detected in anti-HBc positive, HBsAg-negative patients, although the concentration is low. (Korean J Hepatol 2006;12:201-208)

Modified CLIP Score as a New Prognostic Index for Patients with Hepatocellular Carcinoma
Backgrounds/Aims: The prognosis of cirrhotic patients with hepatocellular carcinoma (HCC) depends on both residual liver function and tumor characteristics. The aims of this study was to construct a new prognostic index for HCC patients: the modified CLIP score, and to compare its discriminatory ability and predictive power with those of the CLIP score that is currently the most commonly used integrated staging score in patients of HCC. Methods: A retrospective analysis of 237 cases of HCC diagnosed at Dong-A university hospital was performed. Prognostic analysis was performed for single variables by estimating survival distributions with the Kaplan-Meier’s method, and statistically compared by the log-rank test. Results: Patients had a mean age of 57.5 years and were predominantly males (79.7%). The overall median survival period was 25.7 months. It was correlated to ascites, portal vein thrombosis, AFP, tumor size, and Child-Pugh classification. The median survival period was 41.0, 25.2, 13.8, 13.4, and 6.5 months for CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001), and 42.1, 34.0, 25.7, 14.0, and 6.8 months for modified CLIP scores 0, 1, 2, 3, and 4 to 6, respectively (P<0.001). The Kaplan-Meier’s curve showed that the modified CLIP score had additional explanatory power above that of the CLIP score. Conclusions: The modified CLIP score, compared with the CLIP score, particularly in the score 2- to 3- patient groups of HCC, had greater discriminant ability and survival predictive power, but was not able to discriminate 4- to 6- patient group. (Korean J Hepatol 2006;12:209-220)

The Relationship Between Serum Adiponectin Level and Serum Alanine Aminotransferase Elevation ...
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) comprises a large part of chronic liver diseases. Recently it was reported that adipokines are closely associated with the common risk factors for NAFLD, such as obesity, diabetes, dyslipidemia, and insulin resistance. We aimed to evaluate the changes in serum adiponectin, resistin and leptin concentrations related to alanine aminotransferase (ALT) elevations in Korean men with NAFLD. Methods: We studies 38 men who were diagnosed with fatty liver by abdominal ultrasonography. None had a history of excessive alcohol consumption, autoimmune hepatitis, inherited or metabolic liver disease or viral hepatitis. The subjects were divided into two groups. One group had normal levels of ALT (n=28) and the other had increased ALT (n=10). We compared anthropometrical parameters, biochemical items and serum adipokine levels between these two groups. Results: Serum adiponectin levels were lower in the increased ALT group than in the normal ALT group (3.89±1.77 vs 7.01±2.54 ?g/dL, P=0.001). But there were no significant differences in serum leptin and resistin levels between two groups (4.02±2.04 vs 3.26±1.41 ng/mL, p=0.245, 80.14±14.8 vs 80.5±11.34 ng/mL, P=0.937, respectively). Multiple linear regression analyses demonstrated that the serum adiponectin level is inversely correlated with serum ALT level and that the serum aspartate aminotransferase (AST) level is positively correlated with the serum ALT level. Conclusions: Our study shows that hypoadiponectinemia is associated with an ALT elevation in patients with NAFLD. Adiponectin may play an indirect role in the development of NAFLD. (Korean J Hepatol 2006;12:221-229)

Nine Cases of Sporadic Acute Hepatitis E in Korea
Hepatitis E virus is an enterically transmitted virus that causes endemic cases of acute hepatitis in many countries in Africa, and Southeast and Central Asia. Sporadic cases of acute hepatitis E also have been reported in developed countries. In non-endemic areas, most of the sporadic cases of hepatitis E are introduced from the endemic areas. Until now, only three cases of acute hepatitis E have been reported in Korea. Recently, we experienced nine cases of acute hepatitis, in which serologic studies showed positive of IgM anti-HEV. We report these as cases of acute hepatitis E. These cases suggest that HEV infection occurs sporadically in Korea and should be considered as a cause of cryptogenic acute hepatitis. (Korean J Hepatol 2006;12:230-236)

A Case of Cholestatic Hepatitis lnduced by Epstein-Barr Virus Infection
Acute viral hepatitis in human can be caused by a large number of viruses with a wide range of clinical manifestations and laboratory findings. EBV is a rare causative agent of an acute hepatitis, during the course of infectious mononucleosis. Hepatic manifestations of EBV are usually mild and resolve without serious complications. EBV is rather uncommonly confirmed as an etiologic agent in acute viral hepatitis of adults and it rarely causes cholestatic hepatitis. We report a case of EBV hepatitis with cholestatic feature that was verified through serum viral marker and liver biopsy. (Korean J Hepatol 2006;12:237-242)

Alcoholic Hepatitis

So Young Jin

Double-contrast MR Imaging for Hepatocellular Carcinoma

Joon Koo Han , Se Hyung Kim

The Korean Journal of Evaluation of the Heptocellular Carcinoma Staging Systems

Soon Ho Um
Background/Aims: The Barcelona Clinic Liver Cancer (BCLC) classification offers a prognostic stratification of patients with hepatocellular carcinoma (HCC). We recently demonstrated the BCLC’s peculiar prognostic ability in a retrospective cohort of HCC patients. The aim of this study was to evaluate the BCLC system prospectively in a subsequent separate group of HCC patients enrolled at the same surgically oriented liver unit. Methods: One hundred and ninety- five consecutive HCC patients were prospectively enrolled and their liver disease was staged before therapy. Unlike the BCLC treatment protocol, nodule size and number were not used as absolute exclusion criteria for radical treatment. Predictors of survival were identified using the Cox model. Results: The median survival time was 23 months overall, and 53, 16, 7 and 3 months, respectively, for BCLC categories A, B, C, and D. In our cohort, BCLC had the best independent predictive power for survival when compared with the Okuda, CLIP, UNOS-TNM, and JIS prognostic systems (linear trend χ2=43.01, likelihood χ2=57.94, AIC 885.98). Moreover, the BCLC classification showed a better prognostic ability than the AJCC-TNM 2002 system in surgical patients. Conclusions: The discriminating power of BCLC staging was prospectively assessed in an Italian cohort of HCC patients treated mainly with radical therapies. [Abstract reproduced by permission of J Hepatol 2006;44:723-31]

2006 EASL Topics : Topics Related to Hepatitis B

Soo Hyung Ryu

2006 EASL Topics : Topics Related to Hepatitis C

Yoon Seon Lee

2006 EASL Topics : Topics Related to Nonalcoholic Fatty Liver Disease

Kang Mo Kim

2006 EASL Topics : Topics Related to Alcoholic Hepatitis

Byung Seok Lee

2006 EASL Topics : Topics Related to Portal Hypertension and Its Sequels

Jeong Won Jang

2006 EASL Topics : Topics Related to Liver Cirrhosis

Myoung Kuk Jang

2006 EASL Topics : Topics Related to Liver Cancer

Yoon Jun Kim

2006 EASL Topics : Topics Related to Liver Transplantation

Woo Jin Chung

2006 EASL Topics : Topics Related to Acute Liver Failure

Young Suk Lim

Sat, 01 Jan 2000 00:00:01 +0100

Acute Toxic Hepatitis: RUCAM Application to Drug-induced Liver Injury and Its Limitations

Byung Min Ahn

Role of PXR and CAR in Cholestasis

Jeong Ill Suh
Cholestatic liver diseases are characterized by impairments of bile flows and accumulations of biliary constituents such as bile acids and bilirubin. The changes of phase I and II metabolism and the hepatobiliary transport system minimize cholestatic liver injury. These adaptive responses are transcriptionally regulated by several nuclear receptors. Recent studies have revealed that the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR) are key nuclear receptors for regulating many of the adaptive responses noted in cholestasis. PXR and CAR coordinately regulate not only bile acid metabolism and transport, but also bilirubin clearance. PXR and CAR ligands may be useful in the future for the treatment of cholestatic liver disease. (Korean J Hepatol 2006;12:5-15)

Insulin Resistance in Non-Alcoholic Fatty Liver Disease

Jeong Hyun Park
Insulin resistance is the pathophysiological hallmark of various kinds of clinical diseases, including non- alcoholic fatty liver disease. Insulin resistance is the common characteristic of metabolic syndrome and its related features. Insulin resistance is a systemic disease that affects the nervous system, muscles, pancreas, kidney, heart and immune system, in addition to the liver. A complex interaction between genes and environment factors enhances insulin resistance and the phenotypic expression of NAFLD (non- alcoholic fatty liver disease) in individual patients. Advanced fibrotic liver disease is associated with many features of metabolic syndrome, and the risk of progressive liver disease should not be underestimated for the individuals suffering with metabolic disorders. Abnormalities of insulin signaling can cause the state of insulin resistance, but there is no clear cut scientific evidence that distorted insulin signaling is the primary pathophysiological defect. Increased adipose tissue mass can cause peripheral tissue insulin resistance via the changes of the adipocytokine secretory patterns. We discuss in this article the sequences of the insulin signaling cascades and the possible molecular targets of insulin resistance, the humoral “cross talk” between the distorted secretory patterns of the adipocytokines, and the peripheral tissue insulin resistance along with the pathophysiology of NAFLD. (Korean J Hepatol 2006;12:16-30)

Peginterferon Alfa-2a plus Ribavirin for Initial Treatment of Chronic Hepatitis C in Korea
Background/Aims: Combination therapy with peginterferon and ribavirin is a standard therapy for western patients with chronic hepatitis C; however, its efficacy remains unclear in East Asian patients. We evaluated the efficacy and safety of administering peginterferon alfa-2a plus ribavirin in native Korean patients with chronic hepatitis C. Methods: Seventy-five patients with detectable HCV RNA (52.0% male, median age: 50.8 years) were eligible for the study. The patients were treated with peginterferon alfa-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks (for genotype non-1, n=46) or 1000-1200 mg/day for 48 weeks (for genotype 1, n=29). The early virologic response (EVR), the end of treatment virologic response (ETVR), the sustained virologic response (SVR), the biochemical response and the adverse event were analyzed. Results: EVR was seen in 86.2% of the patients with genotype 1. The ETVR was 58.6% in the genotype 1 group and 84.8% in the genotype non-1 group (P=0.02). The overall SVR was 70.7%: 55.2% in the genotype 1 group and 80.4% in the non-1 group (P=0.04). The sustained biochemical response was 64.0%. Multivariate analysis showed that the baseline HCV RNA level (Odds ratio: 0.045, 95% CI: 0.011-0.183, P<0.001) and genotype (Odds ratio: 0.247, 95% CI: 0.063-0.969, P=0.045) had an independent effect on the SVR. Neutropenia, anemia, flu-like symptoms and itching were the common adverse events. Aggravated liver function led to discontinuation of therapy for six patients. Dose modification in twenty-nine patients was effective without producing a significant reduction of the SVR. Conclusions: Our data suggest that the efficacy of peginterferon plus ribavirin therapy in Koreans is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C patients. The baseline HCV RNA level and the genotype can be significant factors influencing the SVR. (Korean J Hepatol 2006;12:31-40)

Survival Analysis for Patients with Hepatocellular Carcinoma according to Stage, Liver Function ...
Background/Aims: Hepatocellular carcinoma (HCC) is 3rd leading cause of cancer in Korea and the prognosis for HCC patients is poor. For assessing the present treatment outcome, this study analyzed the three-year survival rate (3-YSR) and the prognostic factors for patients with HCC in Korea. Methods: Between November 2000 and December 2003, 905 patients with HCC who were diagnosed and treated at the National Cancer Center Korea were enrolled in this study. The clinical variables, tumor characteristics and survival periods were analyzed. Results: The mean age of all patients was 56.2±10.3 years and 732 (80.9%) patients were male (M:F=4.2:1). 508 (56.1%) patients died and the median survival period was 15.3 months. The overall 3-YSR of the patients with modified UICC stage I, II, III, IVa and IVb were 67.4%, 65.2%, 30.7%, 9.0% and 5.0%, respectively. The modified UICC stage could not differentiate stage I from II, and stage IVa from IVb, on the 3-YSR. The 3-YSR of the Child-Pugh class A patients with modified UICC stage I or II was 85.4% by surgical resection and it was 69.6% by transcatheter chemoembolization (TACE), respectively (P= .461), and those values for patients with stage III were 49.2% and 36.8%, respectively (P=.081). As compared with systemic chemotherapy or conservative therapy, TACE increased the survival rate more for the Child-Pugh class A patients with stage IV. The independent prognostic factors were serum AFP, portal vein thrombosis, the Child-Pugh classification and the stage of HCC. Conclusions: This follow-up study will be helpful in assessing the results of treatments for HCC and it will provide data for the establishment of a more effective treatment strategy. (Korean J Hepatol 2006;12:41-54)

Clinical Features of Liver Abscess Developed after Radiofrequency Ablation and Transarterial ...
Background/Aims: Radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) have been applied for treating hepatocellular carcinoma (HCC), but procedure-related complications can be a serious problem. This study was conducted to evaluate the clinical features of HCC patients who developed liver abscess after RFA and TACE, as compared to those patients without malignancy. Methods: In our center, from December 1999 to March 2004, 31 cases of liver abscess developed after local treatment of HCC (13/751 after RFA and 18/8417 after TAE), which correspond to 5.1% of the total cases (602) of liver abscess. We evaluated the patients’ clinical features, the abscess characteristics, the bacteriology, treatment modality, hospital days and mortality, as compared to those characteristics of 263 abscess patients without malignancy. Results: The time required to diagnose liver abscess was longer in the TACE group (24.8±16.5 days) compared to that of the other two groups (12.2±9.0 days in the RFA group, 9.6±7.5 days in the controls, P=0.001). Gas-forming liver abscess is most frequently found in the RFA groups (76.9%). There were more hospitalized days for the TACE groups than for the RFA group and the controls (34.7±19.8 vs. 15.2±9.2 vs. 18.6±10.9 days, respectively, P<0.001). Two patients (11%) in the TACE group died of sepsis and liver failure. Conclusions: For the patients with prolonged fever after RFA and especially after TACE for HCC, a diagnosis of liver abscess should be suspected earlier to reduce the morbidity and mortality due to liver abscess per se and also the sepsis-related decompensation of the liver. (Korean J Hepatol 2006;12:55-64)

Effect of Low Dose 5-Fluorouracil and Cisplatin Intra-arterial Infusion Chemotherapy in ...
Background/Aims: Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of repeated arterial infusions of low dose cisplatin and 5-fluorouracil (FU) in patients with advanced HCC with decompensated cirrhosis. Methods: Between January 1995 and December 2003, a total of 79 decompensated cirrhotic patients having HCC and PVT were enrolled and divided into 2 groups. Group 1 (n=40) received intra-arterial infusion chemotherapy with cisplatin (10 mg for 5 days) and 5-FU (250 mg for 5 days) via an implanted chemoport every 4 weeks’ and group 2 (n=39) was managed with only conservative treatment. Results: The two groups were well matched with respect to the features relating to the prognosis, including age, gender and the Child- Pugh class. Although diffuse tumor involvement, main portal vein tumor thrombosis and bi-lobar involvement were more frequent in group 1, the median survival period of group 1 was significantly longer than group 2 (5 months vs. 3 months, respectively, P=0.016). Also, the 1-year survival rate of group 1 (7.5%) was higher than that of group 2 (5.1%) (P=0.016). When we analyzed the patients with the Child class B, the survival benefits of intra-arterial chemotherapy were more significant (P=0.008). Conclusions: Intra-arterial chemotherapy consisting of low dose 5-FU and cisplatin achieved favorable results for advanced HCC patients who had decompensated cirrhosis, and it showed better survival in selected patients. This therapy may be useful as a palliative treatment for HCC patients with decompensated cirrhosis. (Korean J Hepatol 2006;12: 65-73)

Clinical Experience of 48 Acute Toxic Hepatitis Patients
Background/Aims: Although many individual cases of toxic hepatitis have been reported in Korea, there are few comprehensive systematic studies on acute toxic hepatitis. The first aim of this study is to investigate the frequency and clinical characteristics of acute toxic hepatitis patients. The second aim of this study is to investigate the efficacy of steroid therapy for immunoallergic idiosyncrasy. Methods: Between March 1998 and March 2004 forty eight patients were included in this study. The medical records were reviewed retrospectively. Acute toxic hepatitis was diagnosed by score of more than 3 in RUCAM criteria. All the patients were tested for hepatitis A, B and C. Other tests included antibodies to CMV and EBV, ANA, AMA and SMA. Results: Seventy-three percent of the patients were female and the mean age of the patients was 47. Twenty cases of acute toxic hepatitis (42%) were related to prescribed medications. The other causes were herbs (35%) and traditional therapeutic preparations (23%). Common symptoms were jaundice (35%), fatigue (10%), fever (9%) and abdominal pain (9%). The biochemical pattern of hepatotoxicity was divided into three groups: hepatocellular (81%), mixed (13%), and cholestatic types (6%). Three patients who have prolonged and severe jaundice were classified into immunoallergic idiosyncrasy based upon clinical and histologic findings. Prednisolone was prescribed in all three cases whose bilirubin levels had been higher than 15 mg/dL for at least 7 days. Jaundice and the laboratory findings rapidly improved within 8 days since the treatment began. Conclusions: In a demographic point of view, most patients of acute toxic hepatitis were middle aged women. Jaundice was the most commonly observed symptom. Prescribed drugs were the most common cause of acute toxic hepatitis. Although most cases of toxic hepatitis will recover with supportive care after cessation of the causative agent, steroid treatment may be helpful for the patients with severe jaundice patients who have immunoallergic idiosyncrasy. (Korean J Hepatol 2006;12:74-81)

Clinical Features of Fulminant Hepatic Failure in a Tertiary Hospital with a Liver Transplant ...
Background/Aims: Striking geographic differences have been noted in the etiology of fulminant hepatic failure (FHF). The prognosis of patients with FHF who do not receive liver transplantation in a timely manner is quite dismal. This study intended to identify the etiology and outcome of FHF in Korean adults and to examine the role of urgent living-donor liver transplantation (LDLT) for treating this unique situation. Methods: We identified all the adult FHF patients who were referred to our unit between 1999 and 2004. FHF was defined as severe acute hepatitis complicated by the rapid development of hepatic encephalopathy within 8 weeks of the initial symptoms in the patients without a previous history of liver disease. Results: One hundred fourteen patients (47 males and 67 females) were identified. The mean age was 39.5±15.3 years. Drugs were the most common cause (28.1%) of FHF (herbal medications, 9.6%), and acute viral infection accounted for 23.7% (HBV accounted for 15.8%). Indeterminate etiologies were noted in 34%. The 90-day survival rate of the nontransplant group was only 15%. Fourteen patients received liver transplants (13 right- lobe LDLT, 1 cadaveric whole liver), and 12 of these (85.7%) survived and showed good graft function during 22 months of median follow-up. Conclusions: Although the causes of FHF in Korea were diverse, HBV infection and herbal medications were responsible for a significant proportion of the cases. Since urgent LDLT improved the overall survival rate of patients with FHF, this should be considered as an important treatment option for patients suffering with FHF. (Korean J Hepatol 2006;12:82-92)

Protein Expression Profiles in a Rat Cirrhotic Model Induced by Thioacetamide
Background/Aims: The reactive oxygen species from thioacetamide (TAA) induces rat liver cirrhosis that resembles the human disease, and it can serve as a suitable animal model for studying human liver cirrhosis. The aim of this study was to identify the molecular protein signatures via a proteomics approach with using a rat model with TAA-induced liver cirrhosis. Methods: Male Wistar rats were treated with 0.3 g/L TAA in their drinking water. The animals were then sacrificed at 9 and 30 weeks after TAA administration. The development of liver cirrhosis was observed with histological study. The livers were processed for proteins extraction and the proteins were analyzed by 2-dimensional electrophoresis. The proteins were identified by matrix-assisted laser desorption ionizing time-of-flight mass spectrometry and this was validated by immunohistochemical staining. Results: On the proteomics analysis of the liver tissues, a total of 88 proteins showed significant change in their expression between the controls and the cirrhotic rats. When the proteins were categorized by their function, they included ECM/cellular skeleton, cell proliferation/death signal, metabolism, DNA damage/stress and immune response related proteins. The level of expression gradually increased up to 30 weeks for interleukin-6 (IL-6) precursor, transforming growth factor-beta (TGF-β) induced protein, TIMP-1 and MMP-9. Cytochrome P450 2B, which is required for the metabolic activation of TAA, also showed the same increasing pattern. In contrast, the expression level of the proteins did not show a significant change at 9 weeks, but this increased to 3-fold at 30 weeks for carbonic anhydrase VII, ras related protein Rab 6, Annexin A2, neurofibromatosis type 2 and aldehyde dehydrogenase. Conclusions: This study showed that there is a repertoire of proteins during the development of liver cirrhosis via TAA. In this model, IL-6, TGF-β, MMP-9 and TIMP-1 were reconfirmed as the molecular signatures during the development of TAA-induced liver cirrhosis. (Korean J Hepatol 2006;12:93-102)

Toxic Hepatitis Associated with Carp Juice Ingestion
The potential hepatotoxicity of herbal remedies and/or health foods is usually ignored in daily life. There have been cases showing the toxic hepatitis and renal failure associated with the ingestion of raw carp bile. We experienced a case of toxic hepatitis without any evidence of renal failure that was associated with carp juice ingestion. The clinical manifestations were characterized by nausea and vomiting after the ingestion of carp juice for 3 months. The diagnosis of toxic hepatitis was made on the basis of the patient’s history, laboratory data, RUCAM (Russel Uclaf Causality Assessment) and the results of ultrasonography guided liver biopsy. The patient showed rapid improvement after instituting supportive therapy. (Korean J Hepatol 2006; 12:103-106)

A Case of Infiltrative Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis ...
A 63-year-old HBsAg-positive male patient was admitted for the evaluation of a liver mass that was detected on ultrasonography. Spiral computed tomography (CT) revealed infiltrative hepatocellular carcinoma (HCC) in the right hepatic lobe with main portal vein tumor thrombosis. His liver function was Child-Pugh class A and the serum alpha fetoprotein level was 7,400 ng/mL. Transarterial chemoembolization (TACE) via the right hepatic artery was performed. Following 3 sessions of TACE every 2 months, spiral CT revealed no evidence of viable tumor. The thrombi within the main portal vein disappeared with performing localized hepatic infarction at the site of the previous tumor. He is still alive 15 months after the third TACE without evidence of recurred tumor and his liver function remains well preserved. This case suggests that TACE might be effective and safe even in the patients with infiltrative HCC with main portal vein tumor thrombosis, if the extent of the tumor is limited and the liver function and portal flow via the collaterals are preserved. (Korean J Hepatol 2006;12:107-111)

Fatty Liver

So Young Jin

Focal Nodular Hyperplasia of the Liver: Imaging Findings with Emphasis on the Findings of ...

Joon Koo Han , Se Hyung Kim

Epidemiology of Hepatocellular Carcinoma in Korea

Joong Won Park , Chang Min Kim

HBV Mutations During Antiviral Therapy in Patients with Chronic Hepatits B

Seong Gyu Hwang

The Incidence Rate of Hepatitis B Virus Surface Gene Variants in Korean Children with ...
Background/Aims: Perinatal infection with hepatitis B virus (HBV) may occur despite immunoprophylaxis. One of the important mechanisms for perinatal prophylaxis failure, might include HBV surface gene variants. Therefore, we screened Korean children, in whom perinatal prophylaxis failed, for HBV surface gene variants. Methods: Thirty-one children with perinatal HBV prophylaxis failure were selected. To amplify the major hydrophilic region of the HBV surface gene, nested PCR with primers targeted to nucleotides 237 to 706 was performed, and then sequencing was done. Results: All cases were shown to be PCR positive for HBV-DNA and genotype C. Nine out of 31 (29%) with perinatal prophylaxis failure had a nucleotide substitution at the major hydrophilic region of the gene; but only two cases (6.5%) had an amino acid substitution. One case was infected by wild type and variants of I126S, and the other by wild type and S114A+I126S, respectively. Conclusions: In Korea, compared to the previous studies of other nations, gene surface variants such as G145R do not appear to play an important role in perinatal immunoprophylaxis failure. (Korean J Hepatol 2005;11:320-328)

The Role of Neuropsychological Testing and Electroencephalogram for Early Detection of Minimal ...
Background/Aims: Minimal hepatic encephalopthy in patients with clinically asymptomatic chronic progressive liver disease may have adverse effects on daily activity. We evaluated the differences in the cognitive function of patients with chronic hepatitis and liver cirrhosis group according to the Child-Pugh classification. Methods: We enrolled 61 consecutive chronic liver disease patients. We used the following study instruments: visual continuous performance test, a spatial memory test, the Wisconsin card-sorting test chosen from Neuroscan and STIM system (Study of the Usefulness of Computerized Neuropsychological Test, Neurosoft company, New York, NY, USA), a global-local processing test and an electroencephalogram (EEG). Results: A significant correlation was found between neurologic abnormalities and the degree of liver disease. The result of the neuropsychological test and the EEG showed that cognitive function decreased according to the severity of chronic liver disease, especially in liver cirrhosis. Cirrhotic patients, especially in Child-Pugh C group, exhibited selective deficits in complex attention and fine motor skills as well as visual spatial perception, with preservation of memory. Conclusions: The STIM and EEG are simple, subjective and reproducible methods and may be used as early detection methods of minimal hepatic encephalopthy. (Korean J Hepatol 2005;11:329-338)

Comparison of Liver Abscess between Diabetic Patients and Non-Diabetic Patients
Background/Aims: Klebsiella pneumoniae is emerging as the leading cause for liver abscess although the most common pathogen was Escherichia coli in the past. Patients with diabetes mellitus are more likely to have a pyogenic liver abscess with gas forming infection; a gas forming pyogenic liver abscess carries a higher morbidity and mortality than the non-gas forming group. This study was conducted to clarify the clinical presentation and prognostic factors for pyogenic liver abscess in diabetic patients compared with non-diabetic patients. Methods: Medical records of 140 cases of patients treated for pyogenic liver abscess from January 1995 through January 2004 were reviewed retrospectively in detail. Results: Among 140 cases of pyogenic liver abscess, underlying diabetes was present in 26.4% (37/140). The clinical presentation between the two groups was not significantly different. The most common organism for the pyogenic abscess was K. pneumoniae in both groups. A gas forming liver abscess was discovered in only the diabetic liver abscess group, 6 of 37 patients (16%). Conclusions: K. pneumoniae was the most common organism cultured in both diabetic and non-diabetic liver abscess. Gas forming liver abscess was more common in diabetic patients than non-diabetic patients. Diabetic patients had more complications than non-diabetic patients.(Korean J Hepatol 2005;11:339-349)

Clinical Outcome of Pulmonary Resections in Patients with Pulmonary Metastasis of ...
Background/Aims: Although the lung is the most common site of extrahepatic spread from hepatocellular carcinoma (HCC), the role of surgery for pulmonary metastasis remains unclear. The aim of this study was to evaluate the efficacy of pulmonary resection in patients with pulmonary metastasis from HCC. Methods: Between July 2000 and July 2004, a total of 6 patients with pulmonary metastasis from HCC underwent curative pulmonary resections. The patients were divided into two groups (Surgery group and Non-surgery group) according to the primary treatment modality of HCC. Medical records, imaging studies, and pathologic reports of the surgical specimens were reviewed. Results: Three patients in the surgery group underwent pulmonary resections for a solitary metastasis after hepatectomy for HCC, and they are all still alive. One of the 3 patients developed a tumor recurrence in the chest wall after pulmonary resection. The survival time after diagnosis of HCC were 79, 122, and 54 months, respectively. The survival time after pulmonary metastatectomy were 49, 39, and 20 months in the three patients. Another 3 patients in the non-surgery group, received a pulmonary metastatectomy; they had either a complete response HCC or partial radiologic response. These 3 patients developed recurrent disease in the liver. One of 3 patients died. The survival time after diagnosis of HCC were 153, 83, 12 months. The survival time after pulmonary metastatectomy were 51, 4, 2 months. Conclusions: The surgical resections of a solitary pulmonary metastasis from HCC in highly selected patients might be an effective treatment modalities for prolonged survival. (Korean J Hepatol 2005;11:350-358)

The Efficacy of Hepatic Arterial Infusion Therapy for Advanced Hepatocellular Carcinoma ...
Background/Aims: Despite the poor response rate of 20-30%, hepatic arterial infusion therapy (HAIT) has been often tried for advanced hepatocellular carcinoma with portal vein tumor thrombosis or ineffective response to other treatments. The factors that predict treatment response to HAIT remain unclear. This study ascertained the response rate to HAIT based on the existence of extrahepatic collateral feeding vessels or anatomical variants. Methods: Forty one patients received repeated HAIT using an implanted drug delivery system. Of the 41 patients, 18 patients were treated with 5-FU, epirubicin and mytomycin-C; 17 patients were treated with 5-FU and cisplatin; and 6 patients were treated with 5-FU, cisplatin and leucovorin. The patients were divided into two groups according to the existence of extrahepatic collateral feeding vessels or anatomical variants. Results: Of the 41 patients, 10 patients (24.4%) showed a complete response (CR) or partial response (PR). Of 41 patients, 22 patients (group A) did not have extrahepatic collateral feeding vessel or an anatomical variant, but 19 patients (group B) did. In group A, 10 patients (45.5%) had a treatment response (CR+PR). However, only one patient (5.3%) had a treatment response (CR+PR) in group B. The response rate in group A was significantly higher than that in group B (45.5 vs. 5.3%; P=0.005). The median survival of group A was significantly longer than that of group B (10.8 vs 3.4 months, P=0.031). Conclusions: Hepatic arterial infusion therapy may be useful therapeutic option for patients with advanced HCC, especially in those that do not have extrahepatic collateral feeding vessel or anatomical variant. (Korean J Hepatol 2005;11:359-370)

The Factors Related to the Prognosis of Solitary Hepatocellular Carcinoma after Radiofrequency ...
Background/Aims: Several risk factors, such as size and location, are related to local recurrence after radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC). The objectives of this study were to clarify factors related to prognosis. Methods: From October 1999 to December 2002, we performed RFA for 107 consecutive patients with solitary HCC. We evaluated spiral computed tomography and serum alpha-fetoprotein level every 3 months after RFA. Seven possible factors for prognosis were analyzed using the Cox proportional hazards regression model: tumor size, tumor location, age, sex, etiology, platelet count, and Child-Pugh classification. Overall survival and disease free survival rate were estimated using the Kaplan-Meier method, and differences between two groups were compared using the log rank test. Results: The Kaplan-Meier estimates of overall survival after radiofrequency ablation were 90.5% at 12 months, 67.4% at 24 months and 46.4% at 36 months and disease free survival were 71.4%, 46.7% and 20.9%, respectively. Using the Cox proportional hazards regression model, it was shown that with regard to overall survival and disease free survival, Child-Pugh classification (P=0.001, P=0.026) and platelet count (P<0.001, P=0.002) were statistically significant factors. The other factors did not have a statistically significant relationship to overall survival and disease free survival. Conclusions: The size and location known as local recurrence factors were not statistically significant with regard to survival and disease free survival. The Child-Pugh classification and platelet count, that reflect the liver function at the time of RFA, were significant factors for prognosis. (Korean J Hepatol 2005;11:371-380)

A Case of the Hepatocellular Carcinoma during the Pregnancy and Metastasis to the Left Atrium
A 28-year-old female with a pregnant state of 29^th gestational week was admitted because of nausea and vomiting. MRI showed a huge hepatocellular carcinoma. At the 36^th gestational week, a normal delivery was done. Surgery of hepatocellular carcinoma was done at 20 days after delivery. After 22 months from the operation, pulmonary metastasis was found and resection of lung mass was done. About 3 years after resection, a low attenuating nodule was detected in the left atrial chamber of heart. We report a case of hepatocellular carcinoma with metastatic lesions to lung and heart in a pregnant woman. (Korean J Hepatol 2005;11:381-385)

A Case of Primary Hepatic Leiomyosarcoma with Intrahepatic and Abdominal Subcutaneous ...
Primary hepatic leiomyosarcoma is a very rare tumor of the liver and primary hepatic leiomyosarcoma with Behcet`s disease has not been reported previously. Behcet`s disease is a multisystem disorder presenting with recurrent oral and genital ulcerations as well as ocular lesions; it has rarely been reported in association with malignant disease. We report a case of primary hepatic leiomyosarcoma with intrahepatic and abdominal subcutaneous metastasis in a patient with Behcet`s disease; this is the first report of these findings in Korea. (Korean J Hepatol 2005;11:386-391)

Nodular Regenerative Hyperplasia

So Young Jin — Sat, 01 Jan 2000 00:00:01 +0100

Spontaneous Total Necrosis of Hepatocellular Carcinoma

Joon Koo Han, M.D. and Se Hyung Kim, M.D.

2005 AASLD Topics : Topics Related to Hepatitis B

Jeong Won Jang

2005 AASLD Topics : Topics Related to Hepatitis C

Do Young Kim

2005 AASLD Topics : Topics Related to Liver Cirrhosis

Chang Hwan Park

2005 AASLD Topics : Topics Related to Hepatocellular Carcinoma

Young Suk Lim

2005 AASLD Topics : Topics Related to Liver Transplantation

Jai Young Cho

2005 AASLD Topics : Topics Related to Nonalcoholic Fatty Liver Disease

Sang Hoon Park

Assessment and Current Treatment of Portal Hypertension

Soon Koo Baik

Bacterial Translocation in Liver Cirrhosis

Jung Hyun Choi

Clinical Outcomes after Discontinuation of Lamivudine in Chronic Hepatitis B Patients with ...
Background/Aims: The therapeutic strategies of applying adefovir for treating lamivudine resistant HBV mutants are controversial. Thus, we observed the clinical outcomes after discontinuation of lamivudine to establish the timing to initiate adefovir therapy. Methods: Fifty chronic hepatitis B (CHB) patients with lamivudine resistant HBV mutants who had received lamivudine for more than 12 months were included in the study. We investigated the clinical outcomes at 6 months after the end of treatment (EOT). We compared the serial clinical outcomes among respective groups based on serum ALT at the EOT and the clinical characteristics of patients with or without acute exacerbation (AE) and the HBeAg loss. We also investigated the predictive parameters of AE and HBeAg loss. Results: Fifteen patients (30%) had experienced AE at 6 months after the EOT. Four patients received antiviral agents because of their hepatic decompensation. Patients with AE had higher serum ALT values and lower HBV DNA titers at EOT compared with those patients without AE. Serum ALT at the EOT was the predictive parameter of AE. Eight patients (21.6%) had newly developed HBeAg loss at 6 months after EOT. The total bilirubin at EOT was the predictive parameter of HBeAg loss. Conclusions: CHB patients with lamivudine resistant HBV mutants had favorable clinical outcomes at 6 months after EOT. Therefore, we can consider observing the clinical courses after discontinuation of lamivudine and it is not always required to overlap the adefovir for treating lamivudine resistant HBV mutants except for the treatment of patients with a high risk of developing decompensation. (Korean J Hepatol 2005;11:227-242)

Usefulness of Reagent Strips for the Diagnosis of Spontaneous Bacterial Peritonitis
Background/Aims: Spontaneous bacterial peritonitis (SBP) is one of the potentially life-threatening complications for patients with liver cirrhosis, and it has a mortality rate of over 20%. Early diagnosis of SBP and immediate use of an adequate antibiotic therapy are very important for achieving a better prognosis. The aim of our study was to assess the usefulness of reagent strips for making the rapid diagnosis of SBP. Methods: A diagnostic paracentesis procedure was performed upon hospital admission in 257 cirrhotic patients (187 males, 70 females; mean age: 54 years) with ascites. Each fresh sample of ascitic fluid was tested using a reagent strip, and the result was scored as 0, 1+, 2+ or 3+. The leukocyte count, polymorphonuclear cell count, blood bottle culture, and chemistry of ascites were also done. Results: We diagnosed 79 cases of SBP and 2 cases of secondary bacterial peritonitis by means of the polymorphonuclear cell count and the classical criteria. When a reagent strip result of 3+ was considered positive, the test`s sensitivity was 86% (70 of 81), the specificity was 100% (176 of 176), and the positive predictive value was 94%. Furthermore, when a reagent strip result of 2+ or more was considered positive, the test sensitivity was 100% (81 of 81), the specificity was 99% (174 of 176), and negative predictive value was 99%. Conclusions: The use of reagent strips is a very sensitive and specific tool for the rapid diagnosis of SBP in cirrhotic patients. A positive result should be an indication for empirical antibiotic therapy, and a negative result may be useful as a screening test to exclude SBP. (Korean J Hepatol 2005;11:243-249)

A Clinical Study of Pyogenic Liver Abscess at Two Different Local Hospitals
Background/Aims: Despite the improvement of personal and social hygiene, pyogenic liver abscess is still a common disease. We compared the incidence, infection route, underlying disease and major complications between two different local hospitals. Methods: We reviewed the clinical data of 100 patients with pyogenic liver abscess who were treated at Seoul and Guri Hanyang University Hospital from 1999 to 2003. Results: There were 64 males and 36 females in the study group; they were aged from 19 to 94 years with a mean of 56.5 years. Every year 19 to 23 pyogenic liver abscess patients were admitted to both hospitals. The most common organism isolated was Klebsiella pneumoniae in both local hospitals. In the Seoul hospital, diabetes (40.9%) was most common associated condition. In the Guri hospital, biliary tract disease or a history of hepatobiliary surgery (54.2%) was the most common associated condition. Catheter drainage and/or percutaneous needle aspiration were established as the standard treatment modality. Conclusions: In both regional hospitals, the incidence of pyogenic liver abscess did not decrease and Klebsiella pneumoniae was the most common organism. Diabetes and biliary tract disease, including, previous hepatobiliary surgery, were the most identifiable underlying disease. (Korean J Hepatol 2005;11:250-260)

A Prospective Study on the Prevalence and Clinical Significance of Autoantibodies in Patients ...
Background/Aims: Exclusion of liver disease from other causes such as autoimmune hepatitis is necessary for diagnosis of nonalcoholic fatty liver disease (NAFLD). However, there has been no study on the prevalence and significance of autoantibodies in the patients with clinically suspected NAFLD in Korea, where hepatitis B is endemic and autoimmune hepatitis is relatively uncommon. Methods: We prospectively tested for anti- nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-mitochondrial antibody (AMA) in 135 serially enrolled patients with suspected NAFLD. We compared the clinical characteristics and biochemical indices of the ANA-positive or ASMA-positive group with those of the autoantibody-negative group. Results: Sixteen patients (11.8%) had serum autoantibodies; there was ANA in 8 patients (5.9%), ASMA in 7 (5.1%), and AMA in 2 (1.5%). Both ANA and AMA were positive in one patient. The ANA-positive or ASMA-positive group showed an older age (49.5±13.0 vs. 42.0±10.9 years, respectively, P=0.018) and higher levels of serum globulin (3.1±0.4 vs. 2.9±0.4g/dL, respectively, P=0.037), compared with the autoantibody-negative group. Two cases with positive ANA or ASMA fulfilled the diagnostic criteria for probable autoimmune hepatitis and two cases with positive AMA were suspected as primary biliary cirrhosis. Conclusions: These findings suggest that autoantibodies could be found in some patients with suspected NAFLD in Korea, AMA-positivity or ASMA-positivity could be associated with old age and high serum globulin, and some of the autoantibody-positive cases could be diagnosed as autoimmune hepatitis or primary biliary cirrhosis. Further studies are necessary to clarify the clinical significance of autoantibody positivity in those patients. (Korean J Hepatol 2005;11:261-267)

Efficacy of Repeated Hepatic Arterial Infusion Chemotherapy in Advanced Hepatocellular ...
Background/Aims: The aim of this study is to elucidate the efficacy of repeated hepatic arterial infusion chemotherapy (HAIC) and different chemotherapeutic regimens for treating patients having advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: From Jan. 1999 and Dec. 2003, a total of 103 patients diagnosed as having HCC with PVTT, but without extrahepatic spreading, were enrolled in this study. They were stratified into two groups. Group I (67 patients) received intraarterial cisplatin (CDDP, 80 mg/m² for 2 hours on Day 1), Group Ⅱ (36 patients) received intraarterial CDDP (60 mg/m² for 2 hours on Day 2) and 5-fluorouracil (5-FU, 500 mg/m² for 5 hours on Day 1-3). They were scheduled to receive at least three consecutive courses of the HAIC at 1 month intervals. Results: Among the 66 patients who completed the protocol, one (2.5%) and seven (17.5%) patients of group Ⅰ, and one (3.8%) and four (15.4%) of group Ⅱ, exhibited complete and partial responses, respectively. The median survival period of all the patients was 6 months. Group Ⅱ showed a tendency to improve the median survival compared to group Ⅰ (8.5 vs 5.0 months, respectively, P=0.45). The most common adverse reaction was nausea (58.2%). However, an elevation of the total bilirubin level was more frequent in Group Ⅰ than in Group Ⅱ (61.3% vs 20.7%, respectively, P<0.05). Conclusions: Repeated HAIC using CDDP achieved favorable results in a few patients with HCC with PVTT, and additional 5-FU may be useful. (Korean J Hepatol 2005;11:268-274)

The Incidence and Clinical Significance of Paraneoplastic Syndromes in Patients with ...
Background/Aims: Patients with hepatocellular carcinoma (HCC) may manifest paraneoplastic syndromes such as hypercholesterolemia, hypoglycemia, hypercalcemia and erythrocytosis. This study was aimed at evaluating the incidence and clinical significance of paraneoplastic syndromes in Korean HCC patients. Methods: The medical records of 165 HCC patients who were diagnosed and died in the Kyung Hee University Hospital, were reviewed retrospectively. The following variables were analyzed: age, gender, hepatitis markers, platelet, liver function test, α-fetoprotein (AFP), Child-Pugh score, tumor features, and the duration of their survival. Results: In total, paraneoplastic syndromes were presented in 43.6% of the HCC patients during the course of their disease. Hypercholesterolemia was solely presented in 14.5%, hypoglycemia in 12.7% and hypercalcemia in 7.8%. The patients who presented with more than 2 syndromes were 8.5%. While 80% of erythrocytosis (4/5) and 51.6% of hypercholesterolemia (16/31) was presented at the time of HCC diagnosis, hypoglycemia and hypercalcemia mainly occurred as terminal events. The patients with paraneoplastic syndromes were younger and had higher rates of portal vein thrombosis, bi-lobar tumor involvement and tumor more of more than 10cm in diameter, compared to those patients without them. The proportion of patients with a serum AFP more than 400ng/mL tended to be higher in the patients with paraneoplastic syndromes. The HCC patients with paraneoplastic syndromes, except for erythrocytosis, had a shorter survival than those patients without them. Conclusions: Paraneoplastic syndromes are not infrequently presented in HCC patients, especially at an advanced stage, and the survival of these patients is relatively shorter. (Korean J Hepatol 2005;11:275-283)

A Case of Primary Hepatic Lymphoma Mimicking Hepatitis
We report here on a case of non-Hodgkin`s lymphoma in which liver involvement was the predominant clinical manifestation. A healthy 44-year-old man presented with upper abdominal pain, hepatosplenomegaly, thrombocytopenia, elevated AST, ALT and bilirubin, and marked elevation of lactate dehydrogenase and alkaline phosphatase. The abdominal CT scan showed only diffuse hepatosplenomegaly and uneven contrast enhancement of the spleen without any definite mass of the liver and spleen. US-guided aspiration biopsy of liver and the histologic examination confirmed a diagnosis of non-Hodgkin`s lymphoma, the diffuse large B cell type. Bone marrow biopsy showed the infiltration of malignant lymphoma cells. PET-CT showed an increased FDG uptake of the liver, spleen and long bones. The patient was treated with combination regimen of cyclophosphamide, doxorubicin, vincristine and prednisone chemotherapy. Even in the absence of a mass lesion or lymphadenopathy, primary hepatic or hepatosplenic lymphoma should be considered in differential diagnosis of hepatitis or liver cirrhosis, especially for patients with diffuse hepatosplenomegaly and markedly elevated LDH. (Korean J Hepatol 2005;11:284-288)

A Case of Primary Small Cell Carcinoma of the Liver
Primary small cell carcinoma of the liver is an extremely rare tumor. Extrapulmonary small cell carcinoma shares many features of pulmonary small cell carcinoma, including the histological appearance, the aggressive clinical behavior and the frequent short-lasting response to either chemotherapy or radiotherapy. We experienced a 56-year-old man with small cell carcinoma that arose in the liver. Abdominal CT scan showed an 8 cm size, low density mass in the segment 4 of the liver and also multiple lymphadenopathies. Chest X-ray showed no abnormal finding, but the chest CT showed a right lower paratracheal lymphadenopathy. The pathological findings showed nests of small round cells with fine granular chromatin, inconspicuous nucleoli and scanty cytoplasm. Distinct and strong immunoreactions were seen for CD56 and c-kit, and sparse immunoreaction was seen for synaptophysin. Thyroid transcription factor-1 showed no immunoreaction. The tumor did not decrease in size despite chemotherapy. We report this case along with a review of the relevant literatures. (Korean J Hepatol 2005;11:289-292)

Focal Nodular Hyperplasia

So Young Jin

Hepatocellular Carcinoma with Unusual Hematogeneous Metastasis to the Small and Large Intestines

Joon Koo Han , Se Hyung Kim

Nutritional Assessment and Management in Liver Cirrhosis

Jong Ho Lee, Ph.D., Jey-Sook Chae, Ph.D. and Kwang-Hyub Han, M.D.1

Problems and Prospects of Stem Cells for Clinical Use in Hepatology

Si Hyun Bae

Association between CCR5 Promoter Polymorphisms and Hepatitis B Virus Infection

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Immunogenetic factors may play a role in determining the susceptibility of an individual to viral infection. CCR5 promoter polymorphisms are known to be associated with HIV infection. However, there has been no report on the association between CCR5 promoter polymorphism and HBV infection. Therefore, we investigated the relationship between the CCR5 promoter polymorphism and HBV infection. Methods: A total of 377 patients were classified into two groups according to their HBV infection status: ① the spontaneous clearance group (SC); HBsAg (-), anti-HBc (+), anti-HBs (+) ② the chronic HBsAg (+) carrier group (CC); HBsAg (+), anti-HBc (+), anti-HBs (-). CCR5 polymorphisms were detected by employing matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS)- based SNP scoring assay, termed Restriction Fragment Mass Polymorphism (RFMP), which exploits the differences in molecular masses between the common allele and rare allele bases of interest. Results: We found that the genotype frequencies of CCR5 A59029G significantly differed between the SC group (n=138) and CC group (n=239) (P<0.05). The CCR5 59029A allelic genotype was associated with an increased risks of chronic infection rather than spontaneous clearance (P=0.002), and the presence of the CCR5 59029G allele was significantly associated with the spontaneous clearance of HBV (P=0.001). Strong linkage disequilibrium between the CCR5-59029 and the CCR5-59353 polymorphic variants was identified. None of the 377 subjects had the CCR5-32 bp deletion mutation. Conclusions: The CCR5 promoter polymorphisms at position 59029 might play a role in the clearance of HBV infection. This primary experimental evidence needs further studies to clarify the clinical usefulness of CCR5 promoter polymorphisms as a target for the screening or treatment of HBV infection. (Korean J Hepatol 2005;11:116-124)

Efficacy and Safety of Adefovir Dipivoxil in Patients with Decompensated Liver Cirrhosis with ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Adefovir dipivoxil is effective in patients with lamivudine-resistant hepatitis B virus (HBV). However, little is known about its role in Korean patients with decompensated liver cirrhosis. We retrospectively evaluated the efficacy and safety of adefovir dipivoxil in patients with decompensated liver cirrhosis with lamivudine resistance, and we compared this to the patients having compensated liver disease. Methods: The patients with lamivudine-resistant chronic liver disease were enrolled and they received adefovir dipivoxil 10 mg daily. The clinical course and the biochemical and virological response of the decompensated cirrhosis group were compared with those of the patients with compensated liver disease group. Results: One-hundred and one patients (the decompensated cirrhosis group, n=53; the compensated liver disease group, n=48) were evaluated. During the following up, 13 patients in the decompensated group and 4 patients in the compensated group dropped out of the treatment (P=0.011). After adefovir treatment, the proportion of patients with serum HBV DNA below 0.5 pg/mL in the decompensated group was less than that in the compensated group (50.9% vs. 83.3%, P=0.001), but the rates of normalized ALT, HBeAg loss and HBeAg seroconversion did not differ. The change of the Child-Pugh score in the decompensated group was 9.1±1.8 to 6.9±1.6 (P<0.001). The biochemical response in decompensated group was slower than that in the compensated group. Renal toxicity was not observed in either group. Conclusions: These results suggest that adefovir dipivoxil would be an effective and safe treatment for patients with decompensated liver cirrhosis with lamivudine resistance, but its effect might be limited and slower for decompensated cirrhosis. (Korean J Hepatol 2005;11:125-134)

Antioxidant Status in Nonalcoholic Steatohepatitis

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Nonalcoholic steatohepatitis (NASH) is chronic liver disease that can potentially progress to end stage liver disease. Oxidative stress to the vulnerable fatty liver has been reported as a key mechanism in development of NASH. Several antioxidant pathways have been identified, but reports that involved quantitative analysis of each antioxidant systems are rare, and these reports have shown various results. So, we investigated antioxidant status and the degree of oxidative stress by measuring several antioxidant enzymes, the total antioxidant status (TAS), and the metabolites of superoxide in NASH patients. Methods: Nineteen NASH patients who were confirmed by liver biopsy and fifteen controls were involved in this study. The levels of body mass index (BMI), AST, ALT, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, TAS, hydrogen peroxide (H₂O₂), and malondialdehyde (MDA) were compared between both groups. The relationship between the histologic severity and the levels of each antioxidants were analyzed in the NASH group. Results: The activities of SOD and catalase were lower in the NASH group. The concentrations of TAS and H₂O₂ were higher in NASH group. The level of GPx and MDA showed no significant differences between both groups. There were no significant relationships between the above variables and the pathological severity. Conclusions: The disturbed metabolism of superoxide due to the decreased activities of SOD and catalase seem to be important in the pathogenesis of NASH. Further investigations about the nonenzymatic secondary antioxidant mechanism are necessary because the TAS was higher for the NASH group. The lack of difference between both groups for the concentration of MDA indicates that mechanisms other than lipid peroxidation also may be important in the pathogenesis of NASH. (Korean J Hepatol 2005;11:135-143)

Clinical Characteristics of Factory Workers with Asymptomatic Liver Function Test Abnormalities ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: The liver function tests (LFTs), such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (γ-GT), have been widely used as screening tests but their low positive predictive value can cause many false positive results. To evaluate the clinical usefulness of these tests, we analyzed the serial LFT results for factory workers, and we compared the risk factors for the groups that were divided according to the serial LFT results. Methods: From June 2001 to October 2001, 1223 consecutive healthy workers in a single factory were enrolled in our study; a questionnaire, LFT and liver ultrasonography were done for all the subjects. The previous LFT results were collected from the Annual health examination survey. According to the abnormalities on the serial LFT, the participants were classified into three groups (abnormal-in-both, alternating or, normal-in-both) and the risk factors were compared among these groups using multiple logistic regression analysis. Results: The prevalence of LFT abnormality on a single test was 16.8%, but on the serial LFT, only 5% of the study participants showed consistent abnormality. The risk factors for the abnormal-in-both group, compared with the alternating group, were liver ultrasonography abnormality such as a fatty liver (odds ratio, 2.2; P=0.026) and a heavy alcohol intake (more than 210 g/week) (odds ratio, 7.2; P=0.064). HBsAg was not a significant risk factor for any of the three groups. Conclusions: In factory workers having serial LFT abnormalities, alcoholic liver disease could be the principal cause of abnormal LFT. Even if the HBsAg were positive in patients with abnormal LFT, there is the possibility of another causes for LFT abnormalities such as alcoholic liver disease and non-alcoholic steatosis or steatohepatitis. (Korean J Hepatol 2005;11:144-156)

Effect of Transjugular Intrahepatic Portosystemic Shunt for Variceal bleeding in Hepatocellular ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Transjugular Intrahepatic Portosystemic Shunt (TIPS) is commonly used in patients with variceal bleeding. However, this procedure is contraindicated in hepatocellular carcinoma patients with portal vein thrombosis. This study was done to evaluate the effect of TIPS in those patients with variceal bleeding. Methods: Between 1997 and 2004, six hepatocellular carcinoma (HCC) patients with portal vein thrombosis were enrolled in this study due to their variceal bleeding. All the patients underwent TIPS placement to treat the variceal bleeding that had not responded to endoscopic treatment. Effective shunt creation was assessed by the decrease of the portal pressure gradient (less than 12 mmHg) or if good patency and flow were seen on a doppler examination. Results: Shunts were successfully created in all the patients and the bleeding was immediately controlled in the active bleeding cases. The bleeding was caused by esophageal varices in one patient and, by gastric varices in five patients. The HCC types were diffuse or massive in five patients, and a single nodule was present in one patient. All the patients had portal vein thrombosis. Rebleeding was noted in two patients at 10 days and 3 months, respectively, due to the shunt occlusion. Hepatic encephalopathy was noted in two patients. The causes of death were hepatorenal syndrome after 2 weeks in one patient, bleeding due to portal hypertensive gastropathy after 3 weeks in another, and cancer progression after 4 months in third patient. Conclusions: For HCC patients with portal vein thrombosis, TIPS can be an effective treatment modality if uncontrolled variceal bleeding presents when using endoscopic hemostasis or pharmacologic therapy. However, further studies are needed. (Korean J Hepatol 2005;11: 157-163)

Spontaneous Resolution of Vanishing Bile Duct Syndrome in Hodgkin`s Lymphoma

Sat, 01 Jan 2000 00:00:01 +0100
Cholestasis in a patient with Hodgkin’s disease is uncommon, and the causes of cholestasis are mainly direct tumor involvement of the liver, hepatotoxic effects of drugs, viral hepatitis, sepsis and opportunistic infections. Vanishing bile duct syndrome (VBDS) represents a very rare cause for cholestasis in this disease. We report here on a case of a 45-year-old man who developed VBDS during the complete remission stage of Hodgkin’s lymphoma. There was no history of hepatitis or intravenous drug abuse, and the patient had negative results for hepatitis A virus, hepatitis B virus, hepatitis C virus, cytomegalovirus, and human immunodeficiency virus. The serological studies for antinuclear antibodies, anti-mitochondrial antibodies and anti-smooth muscle antibodies were also negative. Liver biopsy disclosed the absence of interlobular bile ducts in 9 of 10 portal tracts without any active lymphocyte infiltration and there were no Reed-Sternberg cell in the liver. The patient’s cholestasis was in remission and the serum bililrubin level was normalized after two months without treatment, but tumor recurrence was noted at multiple sites of the abdominal lymph nodes on follow-up abdomino-pelvic computed tomogram. (Korean J Hepatol 2005;11:164-168)

Four Cases of Hepatic Fascioliasis Mimicking Cholangiocarcinoma

Yong Hoon Kim, M.D., Koo Jeong Kang, M.D. and Jung Hyeok Kwon, M.D.1 — Sat, 01 Jan 2000 00:00:01 +0100
Human fascioliasis is a zoonosis caused by Fasciola hepatica, and this is a trematode that infests cattle and sheep. Humans are accidental hosts in the life cycle of this parasite. People are infected by ingestion of the water or the raw aquatic vegetables that are contaminated with the metacercaria. This fluke’s worldwide distribution occurs in areas where sheep, cattle and goats are raised, and there is a life-cycle niche for this fluke in lymnaeid snails. However, it is a rare disease in Korea. We experienced four human fascioliasis which were difficult to differentiate from hepatic malignancy in three patients, and this was misdiagnosed as common hepatic duct tumor in one patient. The patients manifested only vague abdominal symptoms. Intrahepatic fascioliasis showed multiple ill-defined hypoattenuating lesions and filling defects of the lesion lumens on radiologic study. A striking eosinophilia from the patients’ blood was identified and a positive finding of a serum enzyme linked immunosorbent assay for the Fasciola hepatica was also noted in three of four patients. The therapeutic trial with triclabendazole and praziquantel was not successful. (Korean J Hepatol 2005;11:169-175)

Eosinophilic Liver Abscess

So Young Jin — Sat, 01 Jan 2000 00:00:01 +0100

Hepatocellular Carcinoma with Unusual Metastasis to the Gallbladder

Joon Koo Han , Se Hyung Kim — Sat, 01 Jan 2000 00:00:01 +0100

2005 EASL Topics : Topics Related to Hepatitis B

Soo Hyung Ryu — Sat, 01 Jan 2000 00:00:01 +0100

2005 EASL Topics : Related Topics of Hepatitis C

Se Hyun Cho — Sat, 01 Jan 2000 00:00:01 +0100

2005 EASL Topics : Portal Hypertension

Kwang Cheol Koh — Sat, 01 Jan 2000 00:00:01 +0100

2005 EASL Topics : Topics Related to Liver Cancer

Woo Jin Chung — Sat, 01 Jan 2000 00:00:01 +0100

2005 EASL Topics : Topics Related to Liver Transplantation

Yoon Jun Kim — Sat, 01 Jan 2000 00:00:01 +0100

Treatment of Chronic Hepatitis B ; Indication of Drug Therapy in Patients with Chronic Hepatitis B

Mong Cho — Sat, 01 Jan 2000 00:00:01 +0100

Treatment of Chronic Hepatitis B ; Monitoring Patients with Chronic HBV Infection During ...

Yun Soo Kim — Sat, 01 Jan 2000 00:00:01 +0100

Treatment of Chronic Hepatitis B ; Dose and Treatment Duration of Regimen

Young Oh Kweon — Sat, 01 Jan 2000 00:00:01 +0100

Treatment of Chronic Hepatitis B ; Antiviral Therapy in Hepatitis B Carriers Undergoing ...

Jung Hwan Yoon — Sat, 01 Jan 2000 00:00:01 +0100

Treatment of Chronic Hepatitis B ; Prophylaxis Against Hepatitis B Recurrence Following Liver ...

Kyung Suk Suh — Sat, 01 Jan 2000 00:00:01 +0100

Treatment of Chronic Hepatitis B ; The Efficacy of Lamivudine in Korean Patients with Chronic ...

Jong Young Choi — Sat, 01 Jan 2000 00:00:01 +0100

Treatment of Chronic Hepatitis B ; The Efficacy of Alpha-Interferon in Korean Patiens with ...

Kwang Cheol Koh — Sat, 01 Jan 2000 00:00:01 +0100

HBV-specific CD8+ T cells for Sustained HBeAg Seroconversion after Lamivudine Therapy

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Viral suppression of the hepatitis B virus (HBV) can be induced by lamivudine, but the relapse seen in many patients after cessation of lamivudine therapy is troublesome. We thought that the host immune response is important to prevent viral relapse. We compared the frequency of HBV-specific CD8⁺ T cells in the peripheral blood and their expansion capacity after exposure to viral antigen between the patients showing sustained HBeAg seroconversion after use of lamivudine and those patients without sustained response. Methods: We analyzed HBV-specific CD8⁺ T cells that were isolated from the blood of 14 patients with HLA-A2 who showed lamivudine induced HBeAg seroconversion (HBV DNA < 0.5 pg/mL, and the cells were negative for HBeAg) at the end of lamivudine therapy. The purified T cells were directly stained ex vivo, after they had been stimulate with synthetic peptide, using the HBV core 18-27-specific HLA tetramer (Tc _18-27) and monoclonal antibody to CD8. The HBV viral load was quantified by the Amplicor HBV Monitor assay. Results: In patients with a sustained HBeAg response (the sustained group) for a duration of 15.5 months of follow-up, the median number of Tc _18-27 cells out of the 5×10⁴ CD8⁺ T cells was 49.5 (15-135). On the contrary, in patients who experienced relapse (the relapsed group) during a median of 7.5 months of follow-up, the median number of Tc _18-27 cells out of the 5×10⁴ CD8⁺ T cells was 13.5 (0-95). Especially, among patients with a viral load of HBV DNA < 1×10³ copies at the end of treatment, the median number of Tc _18-27 cells out of 5×10⁴ CD8⁺ T cells was 87 (45-135) in sustained group compared to 12 (6-50) in the relapsed group. All patients in the sustained group demonstrated a vigorous expansion of the core 18-27-specific CD8⁺ T cells after stimulation with viral peptide, in contrast to only 3 out of 8 patients in the relapsed group. Conclusions: This study demonstrates that the frequency and functional responsiveness of the circulating HBV-specific CD8⁺ T cells may be important for obtaining a sustained HBeAg response to lamivudine. (Korean J Hepatol 2005;11:34-42)

The Prevalence and Clinical Characteristics of Hepatitis-delta Infection in Korea
Background/Aims: The prevalence of hepatitis delta virus (HDV) infection has been estimated as being approximately 5% among global HBsAg carriers. The anti-delta positive rate in Koreans had been reported as being 0.85% in 1985. While the prevalence of HBV has been decreased from nearly 10% to 5% during the past twenty years, there have been no more studies on the anti-delta prevalence in Koreans. The aim of this study was to estimate the anti-delta prevalence in Koreans and to study the clinical characteristics of anti-delta positive patients in a single center. Methods: Serum anti-delta was measured in one hundred ninety four HBsAg-positive patients who were admitted to our hospital from February 2003 to August 2003. We checked the genotypes of the HBV in the anti-delta positive patients. The clinical features of the anti-delta positive patients were compared to those clinical features of the anti-delta negative patients from the aspect of age, gender, mode of transmission, the positivity of HBeAg and serum HBV DNA. Results: Serum anti-delta was positive in seven patients among the 194 subjects, giving a 3.6% positive rate. Among these seven patients, six had hepatocellular carcinoma (HCC) and the other one had cholangiocarcinoma. All of the anti-delta positive patients had the C genotype of HBV. The anti-delta positive patients showed significantly suppressed HBV DNA replication compared to the anti-delta negative patients. Conclusions: In Koreans, anti-delta was positive mainly in HCC patients with an approximate prevalence of 4%, and this rate has not changed much for the past twenty years. HBV DNA replication was suppressed by HDV infection. (Korean J Hepatol 2005;11:43-50)

Relationship between the Severity of Liver Damage and the Serum Leptin Level for Nonalcoholic ...
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that are mainly characterized histologically by macrovesicular hepatic steatosis. There are two histologic patterns of NAFLD: simple steatosis alone and steatohepatitis. The factors leading from simple steatosis to nonalcoholic steatohepatitis (NASH) are still obscure. The datas from several studies have suggested that leptin could be involved in the progression from hepatic steatosis to steatohepatitis including the fibrosis. We evaluated serum leptin levels in patients with NAFLD to determine whether any relationships existed between the leptin levels and the severity of hepatic inflammation or fibrosis. Methods: We studied 62 patients with NAFLD who were diagnosed at the Hallym University Sacred Heart Hospital from July 2001 to May 2004. We measured the serum leptin level in all cases and liver biopsy samples were obtained from 31 cases. The liver biopsy specimens were graded according to methods described by Brunt. Spearman rank correlations were used to detect the associations between the serum leptin and the various anthropometric and biochemical variables. The relationship between the histologic severity and the serum leptin level was evaluated with logistic regression analysis. Results: Serum leptin levels correlated with insulin, c-peptide, ALT and homeostasis model assessment insulin resistance, but not with BMI, age and gender. Serum leptin level also correlated with hepatic fibrosis, but not with hepatic steatosis or inflammation. However, the serum leptin level was not a significant independent predictor of the grade of hepatic steatosis, inflammation and fibrosis on the univariate analysis. Conclusions: The serum leptin level was not an independent predictor of the severity of liver damage in NAFLD. (Korean J Hepatol 2005;11:51-58)

The Comparative Results of Radiofrequency Ablation versus Surgical Resection for the Treatment ...
Background/Aims: Although surgical resection remains the gold standard of therapy for hepatocellular carcinoma (HCC), only selected patients can undergo resection because of the severity of the underlying cirrhosis or due to the diffuse distribution of the tumor. Radiofrequency ablation (RFA) has recently shown comparable results to surgical resection for the treatment of HCC. We compared the results of RF ablation and surgical resection for the treatment of HCC. Methods: From January 2000 to December 2002, one hundred-sixty patients who had undergone surgical resection or RFA were analyzed retrospectively. The patients with a tumor size less than 5 cm in diameter, with less than 3 tumors in number, with tumor having a Child-Pugh class A classification and no evidence of extrahepatic metastasis were enrolled in the study. The recurrence pattern was classified into local and distant recurrence. We compared the recurrence patterns, the survival rates, the recurrence rates and the complications between the two groups. Results: 1) The local recurrence rate was 9.8% for surgical resection and 18.2% for RFA and the distant recurrence rate were 32.8% and 28.3%, respectively. 2) The 1-, 2- and 3-year overall cumulative survival rates after RFA and surgery were 95.8%, 86.8%, 80.0%, 98.3%, 87.0% and 77.4%, respectively. 3) The incidence of complication was similar between the two groups. Conclusions: Radiofrequency ablation shows comparable results to surgical resection for the treatment of HCC. Therefore, RFA should be considered as the treatment of choice those patients who are not candidates for resection. However, intrahepatic recurrence of tumor after RFA was as frequent as that seen after surgical resection. Further investigation is warranted to clarify whether the current RFA technology could offer improved long-term results. (Korean J Hepatol 2005;11:59-71)

Prostaglandin A2 Induces Caspase-independent Apoptosis in Hepatocellular Carcinoma Cells

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Prostaglandin (PG) A2 has been reported to inhibit the growth of hepatocellular carcinoma cells via activation of apoptosis, although the molecular mechanisms involved have not been clarified, yet. To investigate the mechanism of the PGA₂-induced apoptosis, we analyzed the activation of caspases during the apoptosis of hepatoma cell lines. Methods: Induction of apoptosis by PGA₂ in hepatoma cell lines, Hep 3B and Hep G2, was assessed by DAPI staining of nuclei and agarose gel electrophoresis of genomic DNA. The involvement of caspases was analyzed by immunoblot analysis of poly ADP-ribose polymerase (PARP) and by checking the effect of caspase inhibitors on PGA₂-induced apoptosis. Results: PGA₂ inhibited the growth of Hep 3B and Hep G2 cells, accompanying nuclear condensation and fragmentation, and genomic DNA laddering, which are the hallmarks of apoptosis. The PARP was not cleaved during the apoptosis of Hep 3B and Hep G2 cells and caspase inhibitors such as z-VAD-Fmk and z-DEVD-Fmk exerted no effect on the PGA₂-induced apoptosis. Conclusions: These results suggest that PGA₂ induces apoptosis in Hep 3B and Hep G2 cells via caspase-independent pathway. (Korean J Hepatol 2005;11:72-79)

A Case of Vanishing Bile Duct Syndrome Associated with Hypersensitivity to Allopurinol
Allopurinol is frequently used for the treatment of hyperuricemia and gout. Sometimes, a life-threatening reaction develops, as is illustrated by the following case report. We describe a 60-year-old male patient who was treated with allopurinol because of asymptomatic hyperuricemia, and he was presented with fever, skin rash, eosinophilia, worsening renal function and vanishing bile duct syndrome. In this report, we discussed vanishing bile duct syndrome as a serious side effect of allopurinol, and we briefly reviewed the etiology, prevention, and treatment modalities for vanishing bile duct syndrome. (Korean J Hepatol 2005;11: 80-85)

Primary Adenosquamous Carcinoma of the Liver: A Case Report
Primary adenosquamous cell carcinoma of the liver, a variant of cholangiocarcinoma is very rare disease and its prognosis is known to be very poor. We describe here a case of primary adenosquamous carcinoma of the liver. The patient was a 60-year-old woman who complained of an eight-month history of intermittent upper abdominal pain. Abdominal computed tomography scan revealed a low density mass and intrahepatic duct stones within the dilated left intrahepatic duct in the left lateral segment. Needle biopsy of the mass was done and the histologic diagnosis was cholangiocarcinoma. Left lobectomy was then performed. Upon gross examination, there was a well defined solid mass and intrahepatic duct stone in the dilated bile duct. Microscopically, the tumor was composed of both adenocarcinoma and squamous cell carcinoma. (Korean J Hepatol 2005;11:86-89)

Inflammatory Pseudotumor of the Liver

So Young Jin

Completely Ablated Hepatocellular Carcinoma by percutaneous Radiofrequency Thermal Ablation

Joon Koo Han , Se Hyung Kim

Recent Developments in Radiotherapy of Hepatocellular Carcinoma

Jin Sil Seong — Thu, 01 Jan 1970 09:00:00 +0100
With the accumulation of clinical experiences, the efficacy of radiotherapy has been recognized in management scheme for HCC. While hepatologists are beginning to show less reluctance for applying radiotherapy to the treatment of HCC, it is necessary that

Hepatitis B Virus Surface Antigen: A Multifaceted Protein

Jung Hyun Park — Thu, 01 Jan 1970 09:00:00 +0100
Despite the small size of its genome (3.2 kb) and having only four genes that are encoded within it, the hepatitis B virus (HBV) is one of the most successful viral pathogens in human history. It is estimated that there are about 350-400 million people wo

Reappraisal of HBV Genotypes and Clinical Significance in Koreans Using MALDI-TOF Mass Spectrometry

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: Recent studies have shown that the genotype of hepatitis B virus (HBV) may correlate with the disease natural history and treatment outcome. However, several of these studies used low sensitivity assays in a small number of patients, and

Efficacy of Hepatic Arterial Infusion Therapy for Advanced Hepatocellular Carcinoma Using ...

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: There has been no standard treatment for advanced hepatocellular carcinoma (HCC) until now. The aim of this study was to evaluate the efficacy of hepatic arterial infusion therapy (HAIT) using 5-fluorouracil (5-FU) and cisplatin (CDDP) fo

Positron Emission Tomography with Fluorine-18-Fluorodeoxyglucose is Useful for Predicting the ...

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: Hepatocellular carcinoma (HCC) is heterogenous in terms of its glucose metabolism. Positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) shows various levels of FDG uptake for patients with HCC. This study was designe

The Clinical Report of 1,078 Cases of Hepatocellular Carcinomas: National Cancer Center Experience

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: Hepatocellular carcinoma (HCC) is the third leading cause of cancer and the 5 year survival rate is 9.6% in Korea. To develop a strategy for surveillance and treatments, we studied the recent clinical characteristics of HCC diagnosed at s

Clinical Features and Prognostic Factors of Fulminant Hepatic Failure in Koreans

Thu, 01 Jan 1970 09:00:00 +0100
Background/Aims: There have been scant reports on the prognostic factors of fulminant hepatic failure for selecting the patients who need liver transplantation. We investigated the clinical features and prognostic factors throughout the clinical course of

Porphyria Cutanea Tarda Presenting as Jaundice

Thu, 01 Jan 1970 09:00:00 +0100
Porphyria cutanea tarda (PCT) is a disease characterized by an early appearance of severe photosensitivity with an increase in urinary uroporphyrin excretion and other porphyrins, high isocoproporphyrin fecal levels and an accumulation of protoporphyrin i

A Case of Nodular Regenerative Hyperplasia of Liver that mimicked Primary Biliary Cirrhosis

Thu, 01 Jan 1970 09:00:00 +0100
Nodular regenerative hyperplasia (NRH) of the liver is a rare disease that is characterized by multiple regenerative nodules in the hepatic parenchyma without fibrosis. The exact pathogenesis of NRH has not been established, but it`s been suggested that o

Chronic Graft Versus Host Disease

So Young Jin — Thu, 01 Jan 1970 09:00:00 +0100

Hepatic Involvement in Hereditary Hemorrhagic Telangiectasia

Joon Koo Han , Se Hyung Kim — Thu, 01 Jan 1970 09:00:00 +0100

2004 AASLD Topics : Topics Related to Hepatitis B

Yong Han Paik — Thu, 01 Jan 1970 09:00:00 +0100

2004 AASLD Topics : Topics Related to Hepatitis C

Dong Joon Kim — Thu, 01 Jan 1970 09:00:00 +0100

2004 AASLD Topics : Topics Related to Liver Cirrhosis

So Young Kwon — Thu, 01 Jan 1970 09:00:00 +0100

2004 AASLD Topics : Topics Related to Hepatocellular Carcinoma

Si Hyun Bae — Thu, 01 Jan 1970 09:00:00 +0100

2004 AASLD Topics : Topics Related to Liver Transplantation and Liver Failure

Moon Seok Choi — Thu, 01 Jan 1970 09:00:00 +0100

Optimal Timing and Evaluation of Liver Transplantation

Seung Woon Paik

The Present and Future of Nanotechnology in Medicine

Jung Min Lim

Serologic Markers of Hepatitis B Virus in Pregnant Women in Jeju Island

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Most cases of hepatitis B virus (HBV) are transmitted vertically in endemic areas of HBV. The positivity of serum HBeAg/HBV DNA in pregnant women is associated with vaccine failure. Recently, a national program for HBV vaccines free of charge in neonates born to HBsAg-positive pregnant women is being performed. The aim of this study was to investigate the positivity of serological markers of HBV in pregnant women in Jeju, which is an island separated from the Korean peninsula and a promising cohort to evaluate the effect of a prevention program of HBV infection. In addition, we investigated the geographic differences in the prevalence of HBV infection because it has been reported that the prevalence of HBV has been high in this area previously. Methods: Between January 2001 and December 2002, all women who gave delivery were studied retrospectively. Women between the ages of thirty and forty, who received health screening at the Asan Medical C enter health promotion center in Seoul, were analyzed as controls. Results: During the study period, 1,030 pregnant women (30.8 4.3 years) and 7,270 controls (33.1 5.0 years) were enrolled. The positivity of H BsAg was high in Jeju compared with that of Seoul (6.4% vs. 4.9%) (P =0.036). The positivity of HBeAg/HBV DNA was 31.8% (21/66) in HBsAg-positive pregnant women. The positivity of anti-HBs was low in Jeju compared with that of Seoul (54.5% vs.68.8% ) (P < 0.001). Conclusions: The positivity of HBsAg was found to be high in pregnant women in Jeju. Intensive supervision for HBV infection in pregnant women should be given in this area. (Korean J Hepatol 2004;10:191-196)

The Prevalence of Metabolic Syndrome in Patients with Nonalcoholic Fatty Liver Disease
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, obesity, and insulin resistance, which are the main features of metabolic syndrome. First, we examined the prevalence of metabolic syndrome among patients with NAFLD . We then compared the prevalence of metabolic syndrome in simple steatosis with that in nonalcoholic steatohepatitis (NASH). Finally, we sought to identify clinical factors associated with the stage of liver fibrosis. Methods: From November 2002 to March 2004, we enrolled consecutive 25 patients with NAFLD from patients visiting outpatient clinic. The 17 controls were healthy persons w ho visited our health promotion center. We compared the clinical and biochemical data of the NAFLD group with those of the control group. Using histologic findings, we divided NAFLD into simple steatosis and NASH. We then compared the clinical and biochemical data of the simple steatosis group with those of the NASH group. Results: Fourteen patients (14/25, 56%) had metabolic syndrome in the NAFLD group. There was no difference in the prevalence of metabolic syndrome between the simple steatosis (5/10, 50%) and the NASH group (9/15, 60%). We found significant differences in cardiovascular risk factors between the two groups, but homeostasis model assessment insulin resistance w as the only significantly different factor between the simple steatosis group and the NASH group. In addition, no difference in histological features was found between NASH with metabolic syndrome and without metabolic syndrome. Conclusions: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. We could not find any cardiovascular risk factors that could predict a severe fibrosis. (Korean J Hepatol 2004;10:197-206)

Changes of Ascites Nitric Oxide According to the Treatment Course in Cirrhotic Patients with ...
Background/Aims: Nitricoxide (NO) is a molecule involved in vascular dilatation and pathogen suppression. It also has immunologic and regulatory functions. Liver cirrhosis is characterized by an increased risk for bacterial infections, including spontaneous bacterial peritonitis (SBP). The role of NO in SBP which develops in cirrhosis has not been clearly established. The aim of this study was to investigate the role of NO in the pathogenesis of SBP and its clinical usefulness for prediction of disease prognosis. Methods: This study was designed to investigate the changes of ascites NO in the course of treatment. Nitricoxide metabolite (nitrites+nitrates [NO x]) was measured by chemilum inescence in 84 ascites samples obtained from 84 cirrhotic patients. Among them , the 38 patients with SBP were treated with cefotaxim e 2.0 g, q 12hr for 7 days. In 24 of SBP patients, ascites was obtained consecutively before treatment (day 0),during treatment (day 2),and after treatment (day 7). Results: Ascites NO levels in the patients w ith SBP (n=38; 82.3 14.4 μM ) were not different from those in patients with sterile ascites (n=46; 54.6 13.0 μM ). There was no significant change of NO levels in sequential ascites samples during antibiotic treatment. A scites NO level before treatment was significantly higher in SBP patients who responded to antibiotics (n=26; 101.86 μM/L) than that in SBP patients who did not respond to antibiotics (n=12; 40.03 μM/L, P =0.044). A significant direct correlation was found between ascites and serum NO levels before treatment (Pearson correlation,r²=0.86,P =0.001). Among the SBP patients, treatment response rate to antibiotics were significantly higher in those patients with pretreatment NO level≥80 μM/L in multivariate analysis. Conclusions: Ascites NO level was not different between ascites from SBP patients and ascites from cirrhotic patients with sterile ascites. There were no changes of ascites NO in SBP patients during treatment. Therefore ascites NO was not useful to predict the progress of SBP. Ascites NO levels reflect serum NO levels, and the patients with higher NO level may have better response to antibiotics. (Korean J Hepatol 2004;10:207-215)

Gastric pH and Helicobacter pylori Infection in Patients with Liver Cirrhosis

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Data from previous studies on gastric acid secretion and the prevalence of H. pylori in liver cirrhosis patients remain poorly defined. H. pylori is a potential source of NH₃, but the possible role of H. pylori in hepatic encephalopathy is not clear. The purpose of this study was to com pare gastric acid secretion, the impact of H. pylori infection, and the production of NH₃ between cirrhotic patients and healthy, matched controls. Methods: Twenty-nine patients with liver cirrhosis (HBV , n=12; Alcohol, n=12; HCV , n=5) were matched with 33 healthy persons for age and sex. N one of the patients or controls were being treated with antacids, H2-receptor blockers or proton pump inhibitors. The pH and NH₃ concentration was measured in gastric juice obtained by endoscopy. H. pylori infection was diagnosed using the rapid urease test. The level of NH₃ in venous blood was also measured. Results: The average gastric pH was significantly higher in cirrhosis patients compared to controls (3.91 vs. 2.99, P < 0.05). In addition, the prevalence of hypochlorhydria (defined as pH > 4) was significantly greater in cirrhosis patients (45 vs. 21% , P < 0.05). In contrast, the prevalence of H .pylori infection (62% vs.58% ) and gastric NH₃ concentrations (3.4 vs.3.3 mM/L ) were similar between both groups. However, venous NH₃ levels were significantly higher in cirrhotics than in controls (63.1 vs.25.2 μM/L ,P < 0.05).T he patients with H .pylori infection had significantly higher gastric NH₃ concentration (3.8 vs. 1.6 mM/L) and gastric pH (3.87 vs. 2.76, P < 0.05) than those without infection, but no significant difference in venous NH₃ levels were detected (39.6 vs. 48.1 μM/L ). In patients with cirrhosis, the presence of H. pylori infection was not correlated with either gastric or blood NH₃ levels. Conclusions: T he gastric pH of liver cirrhosis patients is higher than that of controls and a larger proportion of cirrhotic patients have hypochlorhydria. The prevalence of H. pylori in liver cirrhosis patients was similar to that in controls and no correlation was found between gastric and blood NH₃ levels. Thus, H. pylori infection does not seem to play a major role in generation of elevated NH₃ associated with hepatic encephalopathy. (Korean J Hepatol 2004;10:216-222)

Mucinous Cholangiocarcinoma associated with Clonorchis sinensis Infestation: A Case Report
Mucinous cholangiocarcinoma, characterized by large quantities of mucin production, is a rare subtype of peripheral cholangiocarcinoma and usually shows rapid progression and a fatal outcome. We report here a case of mucinous cholangiocarcinom a in a 69 year-old man, who was infected with Clonorchis sinensis. Histologically, the tumor was an adenocarcinom a with extensive intracellular and extracellular mucin production, up to 70% of the tumor mass and there was frequent lymphovascular invasion of the tumor cells. The liver adjacent to the mass contained eggs of C lonorchis sinensis in the bile duct lumen and showed ductal epithelial hyperplasia, mucinous metaplasia and adenomatous proliferation of intramural glands. The patient was treated with a right hepatectomy. Four months after the surgery, the tumor recurred in the soft tissue of the right flank. (Korean J Hepatol 2004;10:223-227)

Extrahepatic Metastasis of Hepatocellular Carcinoma to the Nasal Cavity Manifested as Massive ...
Extrahepatic metastasis of hepatocellular carcinoma (HCC) is not infrequently found during the later stage, regarding that the autopsy report described its prevalence to be up to 50%. The most frequent sites are known to be the abdominal lymph nodes, lung and bone. However, metastasis to the nasal cavity and paranasal sinuses has been seldom reported, and to out know ledge, there is no Korean report describing extrahepatic metastasis of HCC to these sites. Recently we experienced a case of extrahepatic metastasis of HCC to the nasal cavity in a 50 year-old man with massive epistaxis refractory to conservative treatment. He was found to have a mass of soft tissue attenuation occupying the right nasal cavity at CT, which w as biopsy-proven as metastatic HCC. Epistaxis was successfully treated by transcatheter arterial embolization. (Korean J Hepatol 2004;10:228-232)

Extrahepatic Biliary Atresia

So Young Jin

Pseudolesion in Left Lobe of the Liver due to Superior Vena Cava Syndrome

Joon Koo Han , Se Hyung Kim

Peginterferon-alpha and Ribavirin Combination Therapy in Chronic Hepatitis C

Kwang Hyub Han , Young Hoon Yoon

Practice Guideline for Diagnosis and Treatment of Hepatocellular Carcinoma

Joong Won Park
Background/Aims: Hepatocellular carcinoma (HCC) is the 3rd most common cancer. The annual incidence is over 10,000 cases in Korea. While hepatitis B virus is major cause of Korean HCC, the impact of alcoholic liver disease is a rising trend. The 5-year survival rate of HCC is only 9.6%, mainly due late diagnosis, tumor biology and underlying chronic liver diseases. Because almost eighty percent of HCC is diagnosed in late, not early stages, a nationwide surveillance program to screen high risk groups (HBV or HCV carriers or liver cirrhosis, over 40 years old) was launched last year and a practice guideline, with special emphasis on advanced stage HCC was formulated. Methods: Forty-five experts from KLCSG and the National Cancer Center participated in a special committee to develop a practice guideline for HCC. Based on scientific evidence, the consensus was made for diagnosis and treatment strategy after considering the medico-social situation in Korea. Results: Required and optional tests and clinical (non-invasive) diagnosis criteria for HCC are identified. The first decision, based on both Child-Pugh score and modified UICC tumor staging, is to determine operability. The second decision, to determine resectability, is based on localization of the tumor and residual liver function. Chemoembolization or local ablation therapy is allowed for resectable tumors in certain conditions, such as at borderline risk or non-invasively diagnosed. Unresectable tumors are classified into either a group with extensive or macrovascular invasion or distant metastases. Indications of liver transplantation, chemoembolization, local ablation, radiation therapy and chemotherapy for unresectable HCC are presented. Conclusions: This guideline is expected to be useful for clinical management of, and research for HCC patients.(Korean J Hepatol 2004;10:88-98)

Etiology and Clinical Consequence of Spontaneous Acute Exacerbation of Chronic Hepatitis B
Background/Aims: Acute exacerbation (AE) of chronic hepatitis B (CHB) can occur spontaneously, and may be followed by HBeAg clearance. HBeAg seroconversion often coincides with the normalization of liver biochemical tests and clinical remission. The purpose of this study was to identify the etiology and the clinical consequence of severe AE in Korean patients with CHB. Methods: The medical records of CHB patients with severe AE (defined by the sudden increase of ALT above 400 IU/L) who were admitted to Kyung Hee University Hospital between January 1992 and December 2001, were reviewed retrospectively. Forty-four patients were included in the severe AE group. Results: The most common etiology of severe AE was spontaneous exacerbation (77%). Drugs (16%), alcohol (5%), and HCV coinfection (2%) were suspected of causing AE in the remaining patients. HBeAg seroconversion at 12, 18, and 24 months following severe spontaneous AE was 18.5%, 40.7%, and 48.1%, respectively. These were significantly higher compared to CHB patients without AE (4.3%, 4.3%, and 10.9%, respectively). Seroconversion within 3 months, however, occurred in only 15% of CHB patients with AE. There was a tendency to progress to liver cirrhosis more frequently in the patients with AE as compared to the patients without AE (17.6% vs. 5.5%, P<0.08). Conclusions: Severe AE in patients with CHB is mainly caused by spontaneous exacerbation. Although HBeAg seroconversion occurs frequently in these patients, the rates are relatively low compared to those reported in other countries and early seroconversion is expected only in a small proportion. Further studies will be warranted to determine the efficacy of the early use of antiviral agents at the time of AE.(Korean J Hepatol 2004;10:99-107)

The Clinical Meaning of the Emergence of Viral Breakthrough during Lamivudine Treatment in ...
Background/Aims: Viral breakthrough has been considered a major limitation of lamivudine in the treatment of hepatitis B virus related chronic liver disease. Its clinical meaning has not been thoroughly assessed. Methods: 64 patients who showed viral breakthrough during lamivudine treatment were retrospectively reviewed. We evaluated the rate of HBeAg seroconversion and hepatic decompensation after viral breakthrough. Results: After viral breakthrough, serum alanine transaminase (ALT) elevation more than 1.2×upper limit of normal (ULN) was noticed in 40 patients (62.5%). Acute flare (serum ALT elevation >×5 ULN, or serum bilirubin >3 ㎎/dL) occured in 15 patients (23.4%). During the period of follow up (15.0 9.7 months; range, 0-31 months) since viral breakthrough, decreased serum HBV-DNA level to below the detection limit and serum ALT normalization was seen in 15 patients (23.4%). HBeAg seroconversion was noticed in 7 (13.7%) of a total of 51 HBeAg positive patients at base line; in 4 (15.4%) of 26 patients with non-hepatic failure (chronic hepatitis or Child-Pugh class A liver cirrhosis) at base line; and in 2 (40.0%) of 5 patients with non-hepatic failure at base line and acute flare after viral breakthrough. During this period, terminal hepatic decompensation (Child-Pugh class C) or death was noticed in 9 (90.0%) of 10 patients who had hepatic decompensation (Child-Pugh class B or C) at baseline and acute flare after viral breakthrough. Conclusions: Acute flare after viral breakthrough seemed to continue during HBeAg seroconversion and rarely developed into terminal hepatic decompensation or death in patients with non-hepatic decompensation at baseline. Its incidence is not only high but lethal to most patients with hepatic decompensation at baseline. (Korean J Hepatol 2004;10:108-116)

The Short Term Prognosis in Alcoholic Liver Disease with Metabolic Acidosis
Background/Aims: Alcoholic liver disease with metabolic acidosis may have possible causes such as alcoholic ketoacidosis, diabetic ketoacidosis, lactic acidosis. Salicylate, methanol, and ethylene glycol intoxication should also be considered. The aim of this study was to investigate the short-term prognostic factors in patients with alcoholic liver disease with metabolic acidosis. Methods: Clinical data related to twenty-nine patients with alcoholic liver disease and metabolic acidosis was analysed retrospectively. Patients were divided into two groups according to the outcome (survival or death). Past medical history, and physical, laboratory and radiologic data at admission were compared. Results: The amount of daily alcohol intake differed significantly between the two groups (P=0.034), but duration and total amount of alcohol intake did not differ significantly between the two groups (P=0.128; P=0.360). The presence of ascites differed significantly between two the groups (P=0.019). On laboratory testing, the following differed significantly: base excess (P=0.038), hemoglobin (P=0.019), platelet (P=0.040), total bilirubin (P=0.007), albumin (P=0.012), creatinine (P=0.014), phosphorus (P=0.021), chloride (P=0.010), ammonia (P=0.003), prothrombin time (P=0.033), fibrinogen (P=0.011) and D-dimer (P=0.024). Review of the medical history of the patients showed diabetes (10/29), cirrhosis (10/29), and hepatocellular carcinoma (1/29). Combined conditions at admission were sepsis (8/29), pneumonia (7/29), acute renal failure (6/29), rhabdomyolysis (5/29), gastrointestinal hemorrhage (4/29), acute pancreatitis (3/29), acute respiratory distress syndrome (2/29), and acute myocardial infarction (1/29). Conclusions: The amount of daily alcohol intake, base excess, hemoglobin, platelet, total bilirubin, albumin, creatinine, phosphorus, chloride, ammonia, prothrombin time, fibrinogen and D-dimer seemed to be useful parameters in predicting short-term prognosis of patients with alcoholic liver disease with metabolic acidosis. Further study is needed to define the significance of these factors. (Korean J Hepatol 2004;10:117-124)

Clinical Characteristics of Acute Toxic Liver Injury
Background/Aims: Recently, acute toxic liver injury has been reported to be the most common cause of acute hepatitis. The frequency and clinical manifestations of acute toxic liver injury was evaluated. Methods: The medical records of 68 patients demonstrating clinically significant acute toxic liver injury were retrospectively reviewed. Patients with mild biochemical abnormalities were excluded. Results: The annual retrospectively reviewed. Patients with mild biochemical abnormalities were excluded. Results: The annual percentage of toxic liver injury ranged from 50% to 90% among acute hepatitis groups. Among the causes, prescribed drugs (group D) accounted for 55%, herbs or plant products (group H) for 42% and both accounted for 3%. Antibiotics and anti-inflammatory drugs were the most common agents (78%) among group D. The mean age of the patients was 43 and 70% of patients were female. Of the population, common symptoms were jaundice, weakness, fatigue, and nausea. Initial ALT and AST levels were 847 879 and 664 625 IU/L, and initial total bilirubin was 7.5 8.1 ㎎/dL. Acute toxic liver injury occurred after a mean of 32 days after first exposure. Liver injury resolved within a mean of 32 days. Hepatocellular, mixed, and cholestatic type was 45.2%, 32.3%, 22.5%, respectively. Conclusions: Recently, acute toxic liver injury has been the most common cause of acute hepatitis in Korea. Prescribed drugs and herbs or plant products are equally important etiologic agents of toxic liver injury. However, etiologic difference may not affect clinical courses or outcomes. A nationwide investigation of the hepatotoxicity of drugs, herbs or other plant products is required. (Korean J Hepatol 2004;10:125-134)

Clinical Features of Surgically Resected Focal Nodular Hyperplasia of the Liver
Background/Aims: Focal nodular hyperplasia (FNH) is a benign hepatic tumor with few serious complications and no malignant transformation. However, differential diagnosis between FNH and other liver tumors, especially hepatocellular carcinoma, is often difficult. Methods: Clinical features of surgically resected FNH were reviewed. From January, 1995 to February, 2003, 10 patients with surgically resected FNH were enrolled. Their age, sex, results of laboratory examination, imaging studies and pathologic findings were evaluated. Results: Median age was 37.5 years and sex ratio (male:female) was 1.5:1. In 5 cases, resection to exclude hepatic adenoma or HCC was performed. Four cases were diagnosed incidentally after surgery. Four patients had risk factors for HCC, such as hepatitis B virus infection, liver cirrhosis or both. The size of FNH was 3.2 2.2 cm. The most common site of the tumor was segment 6 (30.0%). Differential diagnosis with HCC was difficult in 5 of six cases in whom CT was performed. Although needle biopsies were performed preoperatively in 4 cases, it was difficult to distinguish FNH from hepatic adenoma or HCC. Conclusions: FNH was resected due to uncertainty of diagnosis, or incidentally during hepatectomy in patients with other liver disease. In the former, differential diagnosis with hepatic adenoma or HCC was a major problem despite extensive work-up including dynamic CT or biopsy. (Korean J Hepatol 2004;10:135-141)

A Case of Combined Hepatocellular-Cholangiocarcinoma with Sarcomatous Transformation and Second ...
Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer, featuring both hepatocellular and biliary epithelial differentiations. An intrahepatic tumor may be considered as a metastatic lesion. It has been suggested in the literature that the likelihood of metastasis in the cirrhotic liver is lower than that in the non-cirrhotic liver. A rare case of combined hepatocellular-cholangiocarcinoma and second primary colon adenocarcinoma in a 67-year-old male patient with liver cirrhosis is presented. Histologically, the intrahepatic mass was composed of a spindle cell sarcomatous component; a hepatocellular carcinoma component; and a cholangiocarcinoma component. There were focal transitional regions among the different components. Immunohistochemically, the cholangiocarcinoma component of the intrahepatic mass showed positive reaction for CK-7 but negative reactions for CK-20. The adenocarcinoma of the colon showed positive reactions for CK-20 but negative reactions for CK-7. (Korean J Hepatol 2004;10:142-147)

A Case of Hepatocellular-cholangiocarcinoma Invading the Gallbladder
Metastasis of hepatocellular carcinoma occurs at a relatively late stage of the disease. Hematogenous and lymphatic metastases are the most common routes for dissemination of tumor cells. Hepatocellular carcinoma also extends into the adjacent portal vein and bile ducts. Since there is no peritoneum between the body of the gallbladder and the liver fossa, gallbladder cancer can easily cross the boundary. Gallbladder invasion of hepatocellular carcinoma, however, is quite rare. We report a case of hepatocellular-cholangiocarcinoma in a non-cirrhotic liver that invaded the gallbladder mimicking the gallbladder carcinoma complicated by cholecystitis and liver abscess. (Korean J Hepatol 2004;10:148-153)

Primary Sclerosing Cholangitis

So Young Jin

Hepatic Hemangioma with Arterioportal Shunts

Joon Koo Han , Se Hyung Kim

Topics Related to Hepatitis B

Jong Eun Yeon

Topics Related to Hepatitis C

Joon Hyeok Lee

Topics Related to Liver Cirrhosis

Chun Kyon Lee

Topics Related to Hepatocellular Carcinoma

Il Han Song

Therapeutic Strategy for YMDD Mutants of Hepatitis B Virus

Soo Hyung Ryu, M.D.1 and Young-Hwa Chung, M.D.

Introduction of Bioinformatic Methods for the Gene Function Analysis

Sang Soo Kim

Adequacy of Immediate Lamivudine Trial for Chronic Hepatitis B Patients with Acute Exacerbation
Background/Aims: It has been unclear whether immediate antiviral therapy or observation under the expectation of spontaneous inactivation of hepatitis B virus (HBV), is more appropriate for the treatment of chronic hepatitis B (CHB) with acute exacerbation. We intended to analyze the short-term natural course of CHB with acute exacerbation and evaluate the efficacy of lamivudine. Methods: We analyzed 35 CHB patients with acute exacerbation (positive HBV DNA or HBeAg and ALT>400 IU/L) between March 2000 and May 2003. We regularly checked serum HBV DNA, HBeAg and liver function tests including ALT every 1 to 3 months. If ALT was above 100 IU/L during the follow-up period, patients were treated with 100 mg lamivudine orally once a day. We compared the efficacy of lamivudine use between this group and the group provided with immediate lamivudine trial at their first visit. Results: 27 CHB patients with acute exacerbation were observed without immediate lamivudine trial. In 5 of these patients normal ALT, negative HBeAg and HBV DNA were maintained during 19 months (group 1a). Slightly elevated or normal ALT was maintained without HBeAg seroconversion in 3 patients (group 1b). However, serum ALT flared up above 100 IU/L in 19 patients within 5 months. So, lamivudine was tried on these patients (group 2). The serum HBV DNA was extremely low, being 6.5 pg/mL in group 1a compared to 518.1 pg/mL in group 2. Spontaneous inactivation of HBV was observed in 71.4% (5/7) of patients with HBV DNA less than 20 pg/ mL at the first visit. ALT was lower and HBV DNA was higher in group 2 than the 8 patients who received immediate lamivudine trial at the first visit (group 3). The response rate of lamivudine was similar between group 2, 56.3% (9/16) and group 3, 62.5% (5/8). Conclusions: Spontaneous inactivation of HBV was expected in CHB with acute exacerbation and extremely low level of HBV DNA (less than 20 pg/mL) in a short term follow-up period. Immediate lamivudine therapy might be more appropriate in most CHB patients with acute exacerbation.(Korean J Hepatol 2004;10:22-30)

Pretreatment ALT Level and Histologic Activity as Predictors of HBeAg Loss in Lamivudine ...

Young Oh Kweon, M.D. and Kyung Hee Kang, M.D.
Background/Aims: Lamivudine is a potent inhibitor of hepatitis B virus replication, but an increased incidence of YMDD mutation may be associated with its long term use. Thus, the decision to initiate therapy should be based on variables that are predictive of lamivudine-induced HBeAg loss. The objective of this analysis was to determine patient-dependent or laboratory variables that predict HBeAg loss. Methods: We retrospectively analyzed 99 HBeAg-positive patients with chronic hepatitis B who were treated with lamivudine and followed up for more than 52 weeks. All patients had a liver biopsy before starting lamivudine therapy. HBeAg loss and HBeAg seroconversion after 52 weeks of treatment were defined as endpoints. Results: The overall rates of HBeAg loss and HBeAg seroconversion were 41.4% (41/99) and 37.4% (37/99), respectively. The rates of HBeAg loss increased as pretreatment ALT levels increased (P=0.013) and were highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal, occurring in 56.8% of those patients. The rate of HBeAg loss was higher in patients with more active histologic disease on pretreatment liver biopsy (Grade 1&2 vs. Grade 3&4, 28.3% vs 56.5%, P=0.004). Similar results were seen with HBeAg seroconversion, though seroconversion occurred less frequently than HBeAg loss. Multivariate analysis showed that elevated baseline ALT levels (P<0.05) and histologic activity (P<0.05) were the best independent predictors of HBeAg loss and seroconversion in response to lamivudine. Conclusions: Pretreatment ALT levels and histologic activity were the most important predictors for response to lamivudine.(Korean J Hepatol 2002;10:31-41)

Genotypes of Hepatitis B Virus on Jeju Island
Background/Aims: Hepatitis B virus (HBV) was classified into 8 genotypes by a sequence divergence in the entire genome designated from A to H. HBV genotypes have distinct geographic distributions. Recently, HBV genotypes have been partially found as influencing the clinical manifestation of chronic liver disease in hosts. In Korea, the distribution of HBV genotypes remains unclear. The aim of this study was to evaluate the prevalence of the HBV genotype on Jeju Island. Methods: Hepatitis B virus genotypes were evaluated among 107 hepatitis B carriers residing on Jeju Island. We used single PCR and multiplex-PCR assay with genotype-specific primer pairs for HBV genotypes A-F for the genotyping. Results: 1. Fifty nine samples (55%) were positive for HBV DNA. The positivity was different according to the pattern of HBeAg/ anti-HBe expression, as -/-; 2/3 (66.7%), -/+; 30/73 (30%), +/-; 24/28 (85.7%) and +/+; 3/3 (100%). 2. In the single primer set of genotype-specific PCR, 59 samples (100%) were detected as genotype C and 2 (3%) were also detected as genotype A and B. 3. In multiplex-PCR, 58 samples (98%) were detected as genotype C and only one (2%) as a mixed pattern of genotype B and C. 4. When the PCR products were amplified with universal sense and genotype specific anti-sense from one genotype A, one B, and 2 C, all were included in genotype C. Conclusions: These results suggest that on Jeju Island, almost all HBV genotypes are C.(Korean J Hepatol 2004;10:42-50)

Risk Factors of Morbidity and Mortality Following Surgical Resection for Hepatocellular Carcinoma
Background/Aims: Recently, mortality following surgical resection for hepatocelluar carcinoma has been reduced significantly. Morbidity, however, is still significant. This study evaluated the risk factors leading to morbidity and mortality. Methods: 510 patients who had a hepatic resection form Nov. 1994 to Dec. 2001 were included. The patient demographics showed a mean age of 51.6 years with a male to female ratio of 4:1. The HBsAg was positive in 76.0% and the anti-HCV was positive in 8.2%. The mean tumor size was 5.2 cm, 26.2% of patients had preoperative transcatheter arterial embolization (TAE), and 8.7% had preoperative percutaneous transhepatic portal embolization (PTPE). Limited resection was performed in 259 cases (50.7%), and major resection was conducted in 251 cases (49.1%). Risk factors included age, sex, laboratory findings (liver function test, prothrombin time, albumin, glucose, α-fetoprotein, ICG test), preoperative TAE, PTPE, operation type, operation time, intraoperative transfusion, tumor size, and cirrhosis. Results: The morbidity was 10.5% (54 cases). Operative death occurred in 5 cases (1.0%). Hospital death, including operative death, occurred in 6 cases (1.2%). Five cases were associated with hepatic failure and 1 case was associated with aspiration pneumonia accompanying hepatic failure. Transfusion (P=0.002), glucose (P=0.002), and prothrombin time (P=0.038) were significantly related to morbidity. Age (P=0.028), glucose (P=0.011), and TAE (P=0.046) were significantly related to mortality. Conclusions: Intraoperative transfusion, which is mainly related to intraoperative bleeding, should be reduced if possible to decrease morbidity. Diabetes mellitus patients and the elderly need careful perioperative management.(Korean J Hepatol 2004;10:51-61)

The Role of Angiostatin, Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9 and 12 ...

Sook Kim, M.D.1, Ho Sung Park, M.D., Hyun Jin Son, M.D. and Woo Sung Moon, M.D.
Background/Aims: Tumor angiogenesis, a major requirement for tumor growth and metastasis, is regulated by pro- and anti-angiogenic factors. Hepatocellular carcinoma (HCC) has become a common malignant tumor worldwide. It is characterized by a high vascularity. Methods: We studied the immunohistochemical expression of angiostatin, vascular endothelial cell growth factor (VEGF), matrix metalloproteinase (MMP)-9 and MMP-12, and the relationship between these results and the microvessel density (MVD) in 48 HCC specimens. To determine whether HCC cells express angiostatin per se, we examined the expression of angiostatin, MMP-9 and MMP-12 by Western blotting in four HCC cell lines. Results: Expression of angiostatin and MMP-12 (but not MMP-9) were strongly correlated with decreased MVD in HCCs (P=0.006, P=0.038, respectively). VEGF positive tumors showed a significantly higher MVD than VEGF negative tumors (P=0.01). We divided the 48 cases into the following four groups: group A, angiostatin (+), MMP-9 or -12 (+), and VEGF (-); group B, angiostatin (-) and VEGF (-); group C, angiostatin (+), MMP-9 or -12 (+), and VEGF (+); group D, angiostatin (-) and VEGF (+). There was a significant correlation with MVD among these groups (P<0.001). Angiostatin was detected by Western blotting in 2 out of 4 HCC cell lines and was associated with plasminogen and MMP expression. Conclusions: These results indicate that angiogenesis in HCC is a complex process involving multiple factors including angiostatin, VEGF, and MMP. Our results suggest that angiostatin is generated by MMP-mediated proteolysis of plasminogen in HCC cells.(Korean J Hepatol 2004;10:62-72)

Familial Primary Biliary Cirrhosis in Sisters

So-Young Jin, M.D.

Arterioportal Shunt Mimicking Hepatocellular Carcinoma

Joon Koo Han, M.D. and Se Hyung Kim, M.D.

New Antiviral Therapies for Hepatitis C

Jacqueline O Leary , Raymond T. Chung
Hepatitis C virus (HCV), originally known as non-A non-B hepatitis, was identified and sequenced in 1989.1 Since its molecular cloning, seroepidemiologic studies have revealed that 170 million people worldwide, and 1.8% of the US population, are chronically infected.2-4 End stage liver disease attributable to chronic HCV infection is the leading indication for liver transplantation worldwide, and is a major risk factor for the development of hepatocellular carcinoma.5 ?Antiviral therapy for HCV has not changed dramatically since the introduction of interferon alfa (IFN) in 1986.6 IFN has protean antiviral effects, both direct and indirect, against a large number of DNA and RNA viruses: (1) It prevents viral entry and uncoating. (2) Through the action of the Jak-Stat kinase signal transduction pathway, it induces a large number of host genes that participate in direct inhibition of viral protein and RNA synthesis. For instance, the protein PKR, potently induced by IFN, inhibits both host and viral protein synthesis by phosphorylating and inactivating the eukaryotic translation initiation factor (eIF-2). (3) It upregulates viral antigen expression at the cell surface, increasing recognition of virally infected cells by cytolytic T lymphocytes. (4) It has immunomodulatory effects on T cell and natural killer cell function. The precise mechanism by which IFN acts against HCV is unknown, but recent evidence from RNA replicon and other cell culture systems demonstrate that IFN can act directly to suppress HCV replication.7,8 ?Unfortunately, clinical trials of IFN monotherapy were met with disappointing rates (5-10%) of sustained virologic response (SVR), defined as clearance of HCV RNA using a sensitive qualitative nucleic acid amplification assay 24 weeks after completion of therapy. Only with addition of ribavirin (RBV), a guanosine nucleoside analogue active against other RNA and DNA viruses, to IFN did SVR rates increase appreciably, to approximately 40%.9-12 Its mechanism of action against HCV remains unclear, but data suggest that RBV acts both as an immunomodulator13 and an RNA mutagen.14 ?Because of pharmacokinetic concerns regarding the loss of antiviral efficacy with conventional IFN dosing (thrice weekly), the most important recent advance in the management of chronic hepatitis C has been a manipulation of the IFN alfa molecule to extend its bioavailability. The covalent addition of a polyethylene glycol (PEG) to either the IFN-alfa 2a [PEG-IFN-alfa-2a (40 kD)] or IFN-alfa 2b [PEG-IFN-alfa-2b (12 kD)] in combination with ribavirin was associated with an increase in overall SVR rates to 54-56%.15,16 Unfortunately, to achieve these SVR rates, patients receiving these regimens must often endure significant side effects for up to 48 weeks. Furthermore, persons harboring genotype 1 HCV infection, the most common genotype in the U.S. (75%), experience less than optimal SVR rates of 42- 45%. In addition, the very populations of patients who are most in need of effective antiviral therapy, including persons with decompensated cirrhosis, recipients of liver transplants, and persons coinfected with HIV, experience yet lower SVR rates and are even less able to tolerate curative doses of these medications. ?In view of these limitations, new therapies with greater efficacy, improved side effect profiles, and broader applicability are desirable. This review will consider new agents for hepatitis C in two groups: (1) modifications of currently available therapies, and (2) agents designed to interrupt specific steps in the life cycle of the virus.

Recent Changes of Organism and Treatment in Pyogenic Liver Abscess

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: With the advance of antibiotics and the development of newer imaging techniques, marked changes in etiology, diagnosis, treatment and prognosis of liver abscess have been reported. Methods: We reviewed the clinical data related to 94 patients with pyogenic liver abscess. Results: Of the 94 patients in the study group, the male to female ratio was 1.4:1 and the peak incidence of liver abcess was in the 7th decade. About three quaters (74.5%) of the abcesses were of unknown origin. The predominant location was in the right lobe (70.3%). Single lesion was found in 80 patients and multiple lesions in 14 patients. Pathogens were identified in 67 patients, of which Klebsiella pneumoniae (65.7%) and E. coli (16.4%) were the most common. The modalities of treatment were percutaneous drainage with antibiotics (73.4%), percutaneous aspiration with antibiotics (16.0%), or antibiotics alone (8.5%). The case fatality rate, mainly from associated underlying diseases, was 9 cases (9.6%). Associated diseases were diabetes mellitus (14.9%) and malignancy (10.6%). Conclusions: Our study revealed that the most common organism was Klebsiella pneumoniae and percutaneous needle aspiration and/or catheter drainage were safe and effective treatment modalities for pyogenic liver abscess. Prognosis was determined by the underlying condition.(Korean J Hepatol 2003;12:275-283)

Serum ALT and HBV DNA Levels in Patients with HBeAg-Negative Chronic Hepatitis B

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: HBeAg-negative chronic hepatitis B (CHB) has a poor long-term prognosis. Since no precise clinically relevant HBV thresholds are known in HBeAg-negative CHB, the decision to treat is difficult. The aim of this study was to evaluate the levels of serum HBV DNA and transaminase and to investigate the correlation of these values in patients with HBeAg-negative CHB. Methods: The study analyzed the sera from 82 patients with HBeAg-negative CHB, 61 men and 21 women. The mean age was 45 years. The patients were divided into two groups according to serum ALT levels: the patients with lower ALT level (n=52, UNL<ALT<2×UNL) and higher level (n=30, ALT≥ 2×UNL). The level of serum HBV DNA was determined by the Cobas Amplicor HBV Monitor™ (Roche). Results: The median serum HBV DNA level was 2.7×10⁵ copies/mL in patients with HBeAg-negative CHB. The median serum HBV DNA level of patients with a higher ALT level (1.0×10⁶ copies/mL) was significantly higher than that of patients with a lower ALT level (5.6×10⁴ copies/mL)(p<0.001). The serum ALT level was correlated with serum HBV DNA levels in patients with HBeAg-negative CHB (r=0.416, p<0.001). The serum level of HBV DNA in patients with cirrhosis (median 2.0×10⁵ copies/mL) did not differ from patients without cirrhosis (median 4.7×10⁵ copies/mL). Conclusions: The level of serum HBV DNA was higher in patients with higher serum ALT level than it was in patients with lower serum ALT, and it was closely correlated with serum ALT levels in HBeAg-negative CHB.(Korean J Hepatol 2003;9:284-292)

Predictive Factors and Clinical Outcome of Viral Breakthrough during Lamivudine Treatment for ...
Background/Aims: Long-term treatment with lamivudine causes breakthrough, but the clinical course after lamivudine breakthrough is not well known. The aims of this study were to evaluate the clinical course in lamivudine after breakthrough, and to identify predictive factors of breakthrough. Methods: 124 patients with chronic hepatitis B infection, who represented viral breakthrough during lamivudine therapy, were included. The mean duration of lamivudine therapy and additional lamivudine therapy after breakthrough was 30.5 months and 12.5 months, respectively. Results: The cumulative breakthrough rates at 12, 18, 24 and 36 months were 8, 24, 36 and 52%, respectively. After viral breakthrough, only 4 patients maintained normal ALT levels. 120 patients showed ALT elevation. The number of patients with ALT levels greater than 5 times, and greater than 10 times, the upper normal limit were 67 (56%) and 29 (24%), respectively. While still on lamivudine therapy after breakthrough, 98 patients presented ALT elevation. Only 22 had normalized ALT levels. Hepatic decompensation developed in 2 patients. HBeAg seroconversion after breakthrough occurred in 10 patients. The changing pattern of quantitative HBeAg levels during lamivudine therapy was the only predictive factor associated with viral breakthrough. The mean time of turning points in decrescendo-crescendo patterns of HBeAg levels during lamivudine therapy was earlier than viral breakthrough (9 months vs. 17 months). Conclusions: These results suggested that deterioration of hepatic function can usually be observed after breakthrough. The serial monitoring of serum quantitative HBeAg levels may allow an early recognition of viral breakthrough.(Korean J Hepatol 2003;9:293-303)

Hepatitis B Surface Antigen and Antibody Positive Rates of Children and Adolescents in Jeju

Jung Ho Seo, M.D.
Background/Aims: Korea has been an endemic area of Hepatitis B infection. Recently, the Hepatitis B carrier population has been significantly decreasing because of Hepatitis B vaccination. The aim of this study was to analyse the Hepatitis B surface antigen (HBsAg) and the Hepatitis B surface antibody (anti-HBs) positive rates of children and adolescents in Jeju. Methods: From January 2000 to August 2002, seropositivity of HBsAg and anti-HBs were evaluated by enzyme immunoassay (EIA) in 1,653 pediatric patients. From April 2002 to August 2002, seropositivity of HBsAg and anti-HBs were evaluated by reversed passive hemaglutination (RPHA) in 2,532 students. From July 1994 to February 2003, seropositivity of HBsAg was evaluated by EIA in 1,013 pregnant women. Results: The positive rates of HBsAg and anti-HBs of children and adolescents in Jeju were 2.1% and 70.9%, respectively. The positive rates of HBsAg of pregnant women in Jeju was 4.7% and that of HBeAg in HBsAg positive pregnant women was 38.1%. In children born after 1995, as age increased, HBsAg seropositivity increased significantly and anti-HBs seropositivity decreased significantly. There was no significant difference in testing HBsAg positivity between the RPHA and the EIA tests, but testing anti-HBs positivity by EIA was significantly higher than by RPHA. Conclusions: To reduce HBsAg positive rate, regular testing for anti-HBs by EIA may be indicated until at least 15 years after the primary vaccination schedule, and booster vaccination may be indicated in subjects whose anti-HBs titer was under 10 mIU/mL. 29.1% of children and adolescents in Jeju, therefore, may need to be revaccinated.(Korean J Hepatol 2003;9:304-314)

The Clinical Usefulness of Balloon Occluded Retrograde Transvenous Obliteration in Gastric ...
Backgrounds/Aims: Gastric variceal bleeding is difficult to treat endoscopically because the hemodynamics of the gastric varix are different from that of the esophageal varix. Transjugular intrahepatic portosystemic shunt (TIPS), which has been used widely, does not always result in the regression of gastric varix and it may aggravate the hepatic encephalopathy. Balloon occluded retrograde transvenous obliteration (BRTO) was introduced as a new procedure for gastric variceal bleeding with minimal invasiveness. The purpose of this study was to evaluate the therapeutic effects and complications on follow-up of BRTO as a new treatment option for gastric variceal bleeding. Methods: Patients with gastric variceal bleeding, who were treated with BRTO form September, 2001 to April, 2003, were included in the study. After the definite confirmation of the shunts with abdominal CT, the sclerosing agent, 5% ethanolamine oleate, was injected into the gastric varix during occlusion through gastrorenal shunts. The procedurre was deemed a technical success when the clotting of the sclerosing agent was observed without leakage, and a clinical success when bleeding stopped and the varix decreased in size or was eradicated during the follow-up period (6-23 months, mean: 17.7). Results: Technical success was achieved in 12 of 13 patients (92%) with gastric variceal bleeding. There were no significant side effects. In the one case of failure, the bleeding was controlled with TIPS. Eleven of the 12 patients who had technical success were shown to be clinically successful. The follow-up endoscopic exam showed some aggravation of pre-existing esophageal varices in four patients and a new development of esophageal varices in two patients. Endoscopic variceal ligation was done on one patient in whom esophageal variceal bleeding was present during the follow-up period. Conclusions: BRTO was proven to be a feasible, safe and less invasive procedure than TIPS and found to be an effective treatment of a gastric variceal bleeding. Considering the possible aggravation of pre-existing esophageal varices or the new development of esophageal varices, regular endoscopic examinations might be needed during the follow-up period.(Korean J Hepatol 2003;9:315-323)

The Significance of Urine Sodium Measurement after Furosemide Administration in ...
Background/Aims: The diagnosis of refractory ascites means a poor prognosis for patients with liver cirrhosis. The definition of refractory ascites has already been established, but using the dosage of diuretics that correlates with the definition of refractory ascites in an out-patient department will lower the compliance of the patient, as well as causing serious complications, such as hepatic encephalopathy and hyponatremia, as the dosage of diuretics is increased. Due to this fact, it is very difficult to apply this definition of refractory ascites to patients in a domestic out-patient department. In this study, in situations where there are difficulties in applying the diuretics dosage according to definition of refractory ascites, we tried to find out whether measuring the value of urine sodium after the administration of intravenous furosemide can be the standard in early differentiation of the response to diuretics treatment. Methods: We reviewed 16 cases of liver cirrhosis with ascites and classified them into two groups by the response to diuretics. The diuretics-responsive ascites group was 8 cases and the diuretics-unresponsive ascites group consisted of 8 cases. After admission, we examined the patients’ CBC, biochemical liver function test, spot urine sodium, and 24 hour creatinine clearance. After the beginning of the experiment, all diuretic therapy was stopped for 3 days. Daily we examined the patients’ CBC, biochemical liver function test, and in the 3rd experiment day, we measured 24-hour urine volume and sodium. In the 4th experiment day, after sampling for ADH, plasma renin activity and plasma aldosterone level, we administrated the furosemide 80 mg I.V, and measured the amount of 8 hour urine volume and sodium. Results: The plasma aldosterone level was significantly higher in the diuretics- unresponsive ascites group than in the diuretics-responsive ascites group. In the 4th experiment day, the amount of urine volume and sodium was very significantly lower in the diuretics-unresponsive ascites group than in the diuretics-responsive ascites group (1297.5±80.9 vs 2003.7±114.6 ml, p<0.005, 77.3±8.2 vs 211.8±12.6 mEq, p<0.001). Conclusions: In out-patient departments, the measurement of urine sodium 8 hours after administrating 80 mg of intravenous furosemide, will help in differentiating ascites patients with lower treatment response to diuretics.(Korean J Hepatol 2003;9:324-331)

A Case of Toxic Hepatitis Induced by Habitual Glue Sniffing
The link between toxic hepatitis and exposure to organic solvents is relatively well-documented, but there are no specific laboratory or histologic findings diagnostic of chemical-induced hepatitis. Clinical history, therefore, is very important in making a diagnosis. A history of glue sniffing is sometimes overlooked and glue sniffing has not received much attention as a cause of hepatitis. Toluene, a main organic solvent in glue, is known to cause disturbances in various organs such as the heart, nervous system, liver and kidneys. We present a case of hepatitis in an individual who has sniffed glue for euphoria for 3 years. There is an increasing tendency towards glue sniffing among young adolescents today, so toxicity caused by exposure to organic solvents should be considered as one possible cause of hepatitis in young adolescents.

Autoimmune Hepatitis

Kim Hyeonjeong , Yu Eunsil

Eosinophilic Hepatic Abscess

Han Jungu , Kim Sehyeong

Ultrastructure of Chronic Liver Diseases - Lysosomes and Lysosomal Storage Diseases -

Jeong Gyuwon

Letter to the Editor : Mortality Rate According to CTP Score and MELD Score in Patients with ...

Hwang Seonggyu — Sat, 01 Jan 2000 00:00:01 +0100

New Scoring Systems for Severity Outcome of Liver Cirrhosis and Hepatocellular Carcinoma: ...

Lee Dong Hu , Son Ju Hyeon , Kim Tae Hwa
It has been approximately 30 years since Child-Turcotte-Pugh score has been used in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Recently, new prognostic models such as Model for End-Stage Liver disease (MELD), Short- and Long-term Prognostic Indices (STPI and LTPI), Rockall score, and Emory score were proposed for predicting survival in patients with liver cirrhosis treated by transjugular intrahepatic portosystemic shunt (TIPS). In MELD scoring, three independent variables which showed a wide range of results including serum creatinine, serum bilirubin and international normalization ratio(INR) of prothrombin time were evaluated in log. scale in comparison with simply categorized-into-three scoring system of Child-Turcotte-Pugh. The etiology of liver cirrhosis was applied to the score of MELD: alcoholic or cholestatic, 0; viral or others, 1. Concurrent statistic (C-statistic) of MELD (0.73-0.84) was slightly superior or insignificantly different to that (0.67-0.809) of Child-Turcotte-Pugh score. In February 2002, UNOS status 2a and 2b were replaced with MELD score for priority allocation of liver transplantation. (MELD score does not reflect the severity of patients with HCC or metabolic disorders. For assessing prognosis in patients with liver cirrhosis or HCC, there seems little reason to replace the well established Child- Turcotte-Pugh score, Herein the literatures was briefly reviewed(Korean J Hepatol 2003;9:167-179)

Recurrence and Management of Hepatitis C after Liver Transplantation
Background/Aims: End-stage liver disease caused by viral hepatitis C has been increasing recently in Korea. In this study, we investigated the clinical progress, recurrence, and management of hepatitis C patients who underwent liver transplantation, Methods: We retrospectively reviewed the clinical progress and management of 16 patients (2.7%) with hepatitis C among 587 liver transplant patients from August 1992 to August 2002. Results: Eleven cases among 16 patients were males. The median age was 56±6(42-62) years and the median follow-up period was 6±13 (1-41) months. Thirteen cases underwent living donor liver transplantation and three had cadaveric whole liver transplantation. Clinical recurrence occurred in nine cases (56.3%) and mean time of recurrence was 5.2 months, Histological recurrence cases were eight (50%). A positive result of HCV RNA PCR was found in 90.9%, and all cases of clinical and histological recurrence in groups in the same periods were PCR-positive. Among eight cases showing histological recurrence five patients were managed by ribavirin monotherapy, two patients received interferon and ribavirin combination therapy, and one patient was not treated at all, The serum serum aminotransferase level was normalized in six cases (75%) of them. Conclusions: We observed that the HCV reinfection rate of a transplanted liver was high in this study, as in other reports in the literature, The prevention of HCV recurrence and the management of post-recurrent cirrhotic change are crucial for graft and patient survival. We think customized protocols are needed for every situation of recurrent hepatitis C.(Korean J Hepatol 2003;9:180-187)

Efficacy of Lamivudine Re-treatment and Relapse Patterns after Initial Lamivudine Treatment for ...
Background/Aims: The post-treatment relapse patterns and efficacy of lamivudine re-treatment for relapsed patients have not been clarified. The aims of this study were to evaluate the relapse patterns after discontinuing therapy and the effects of lamivudine re-treatment for relapsed patients after HBeAg seroconversion. Methods: Therapy was discontinued after HBeAg seroconversion in 121 patients. Sixty-six patients were relapsed and included in this study. The duration of lamivudine re-treatment therapy was from 6-35 (mean: 16) months. Post-retreatment monitoring continued for 1-40 (mean: 8,9) months. Results: Among the relapsed 66 patients, 50 (75.8%) had HBeAg reappearance while 16 (24.2%) remained HBeAg negative and anti-HBe positive, The cumulative relapse rates at 3, 6, 12 and 24 months were 27%, 47%, 60% and 66%, respectively, Forty-two relapsers received lamivudine re-treatment, Among them, 33 were HBeAg positive and 9 were HBeAg negative and anti-HBe positive, Response was achieved in 31 of the 42 patients (73.8%). The cumulative response rates at 6, 9 and 12 months were 62%, 69% and 72%, respectively. Six patients (14.3%) developed viral breakthrough, All patients were HBeAg positive chronic hepatitis B. The duration of lamivudine re-treatment was the only predictable factor for response of lamivudine re-treatment. Therapy was discontinued after response in 21 patients, Eleven patients were relapsed, including 6 who were HBeAg positive and 5 who were HBeAg negative. Predictive factors for post-retreatment relapse were age and the duration of additional lamivudine therapy after response, Conclusions: The response rate of lamivudine re-treatment was significantly higher than in initial lamivudine treatments. The response rate of lamivudine re-treatment was significantly higher than in initial lamivudine treatments. The breakthrough and relapse rates, however, were similar in both initial and retreated lamivudine therapy.(Korean J Hepatol 2003;9:188-197)

Outbreak of Hepatitis by Orientia tsutsugamushi in the Early Years of the New Millenium
Background/Aims: Orientia -tsutsugamushi infection is an acute febrile disease due to the accidental transmission through human skin of forest dwelling vector Leptotrombidium larva. The authors observed liver dysfunctions in patients diagnosed with tsutsugamushi disease (Scrub typhus) in the past 3 years and report the data in the hope of bringing attention to this disease in the differential diagnosis of autumn-season hepatitis, especially of non-A, non-B and non-C hepatitis. Methods: Medical records of 22 patients diagnosed with tsutsugamushi disease by the hemagglutinin method between October 2000 and November 2002 were reviewed. Results: Female gender was dominant in the ratio of 3.4:1. Mean age was 56.4±2.6. Admission was between 23rd September and 15th November with the peak between mid October and early November. Fever, being the most common symptom, was observed in 21 cases, myalgia in 13, arthralgia in 12, chills in 6, and skin rash in 6. An incubation period of 7-9 days was most common (10 cases), 13-15 days (4), 10-12 days (3), within 3 days (3), and 4-6 days (2). Average ALT, AST and GGTP were increased to 93.2±17.3 IU/L (18±345 IU/L), 92.5±11.7 IU/L (34-255 IU/L) and 132.2±14.5 IU/L (19-251 IU/L), respectively, but total bilirubin was normal. All the patients improved with doxycycline therapy. Conclusions: Since it usually shows liver dysfunction, it is important to take Orientia tsutsugamushi into consideration in differential diagnosis of autumn-season, febrile hepatic disease.(Korean J Hepatol 2003;9: 198-204)

Prevalence and Clinical Significance of Diabetes Mellitus in Patients with Liver Cirrhosis

Kwon So Yeong
Background/Aims: Impaired glucose tolerance and overt diabetes mellitus (DM) frequently occurs in patients with chronic liver disease. Hyperinsulinaemia and peripheral insulin resistance contribute to the development of DM in these patients. The clinical relevance, however, of DM to their clinical course was not determined. We investigated the prevalence of DM in patients with liver cirrhosis and their chinical characteristics and prognosis. Methods: A total of 606 consecutive cirrhotic patients were enrolled for 5 year. We reviewed all prognosis. findings, clinical courses, and mortality, retrospectively. The cirrhotic patients were divided into two groups according to the presence of DM, and their clinical characteristics and mortality were compared. DM was diagnosed in accordance with National Diabetes Data Group criteria. Results: Among the total of 606 cirrhotic patients (M:F, 482:124), 346 (57.1%) had HBV related disease and 60 (10%) had HCV related disease. Forty-five percent of the patients had a history of habitual drinking. DM was observed in 22.4% of the cirrhotic patients. In the diabetic group, the frequency of HCV infection was significant greater. DM did not affect survival. The DM group, however, appeared to have higher mortality in the patients with Child-Pugh class A cirrhosis during long-term follow up, Only 20.6% of the diabetic patients had normal range blood glucose levels even though most of them received medical therapy, The cases with well controlled blood glucose showed higher survival than poorly controlled cases in the DM group. Conclusions: Cirrhotic patients have a high prevalence of DM, and more frequently are associated with HCV infection. The strict control of blood glucose and the control of infection could be important in prolonging the survival in compensated cirrhotic patients with DM.(Korean J Hepatol 2003;9:205-211)

Assessment of Quality of Life and Associated Factors in Patients with Chronic Viral Liver Disease
Background/Aims: The aim of this study was to measure health related quality of life (HRQOL) in patients with chronic viral hepatitis or cirrhosis and to determine factors associated with more severe impairment. Methods: We conducted a cross-sectional study in which we documented patients` demographic and clinical characteristics and measured their HRQOL using the Korean version of Short form-36. A total of 375 patients were enrolled in the study. We compared patients` HRQOL with that of 750 participants in a control group and assessed the association of HRQOL impairment with clinical parameters. Results: In all except two domains (physical functioning, bodily pain) of SF-36, HRQOL scores were significantly lower in the patient group than in the control group (p<0.001). The difference was more prominent in those domains reflective of mental, rather than physical, health. When patient group was classified as noncirrhosis, child A, B, or C according to modified Child-Pugh classification, severe liver disease was associated with a lower HRQOL score. Interestingly, scores of domains reflective of mental health were decreased from the early stage of disease (noncirrhosis or Child-Pugh A). Those of domains reflective of physical health, however, were decreased only in advanced stages of disease (Child-Pugh B or C). There are weak but significant correlations between SF-36 scores and age, serum albumin, serum bilirubin, and prothrombin time, but no correlation with histologic activity, transaminase level, disease duration, virus type (HBV or HCV) and HBV DNA level. Conclusions: Compared with the control group, patients with chronic viral hepatitis or cirrhosis showed substantial impairment of HRQOL, which is further affected by worsening disease severity. More concern about HRQOL should be warranted in the evaluation of health change due to disease progression or therapeutic trial.(Korean J Hepatol 2003;9:212-221)

Clinical Usefulness of Plasma Activities of Gelatinase (Matrix Metalloproteinase-2 and 9) in ...
Background/Aims: Gelatinase (matrix metalloproteinase (MMP) -2 and 9) has an important role in the pathogenesis of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). In this study, we evaluated the relationship of gelatinase to chromic liver disease. Methods: Four groups of subjects were examined; healthy control (10 cases), chronic hepatitis (18 cases), LC (15 cases), and HCC (28 cases). The plasma of each subject was obtained, and the equal quantification of plasma protein was done. The plasma activities of MMP-2 and 9 were measured by zymography. Results: The activities of plasma MMP-2 in patients with LC were significantly higher than those in controls (p=0.009) and in patients with chronic hepatitis (p=0.011), but not different from those in patients with HCC. The activities of plasma MMP-9 in patients with LC were significantly higher than those in controls, but not different from those in patients with chronic hepatitis or HCC. In patients with LC (regardless of having HCC), the activities of MMP-2 correlated with total bilirubin (r=0.323, p=0.048) and Child-Pugh score (r=0.414, p=0.012). The activities of MMP-2 and 9 were higher in patients with LC (regardless of having HCC) caused by alcohol than caused by HBV (p=0.009 and 0.002 for each one). Conclusions: The plasma activity of MMP-2 may be a useful marker for the diagnosis and determination of the severity of LC. The plasma activity of MMP-9 was not useful for HCC, but may be a marker for alcoholic LC. Further study is needed to determine why the plasma activity of gelatinase was higher in patients with LC caused by alcohol than by HBV.(Korean J Hepatol 2003;9:222-230)

Two Cases of Autoimmnune Hepatitis Associated with Systemic Lupus Erythematosus
Autoimmune hepatitis (AIH) is a chronic necroinflammatory liver disease of unknown cause associated with circulating autoantibodies and high serum globulin level. Systemic lupus erythematosus (SLE) is a disease of unknown etiology in which tissues and cells are damaged by pathogenic autoantibodies and immune complex, of SLE and autoimmune hepatitis has not been clearly defined in the past due to similarities in clinical and biochemical features. A scoring system for the diagnosis of AIH has been established, and AIH and SLE-associated hepatitis have been defined as two different entities, although both have the same autoimmune features such as polyarthralgia, hypergammaglobulinemia and circulating autoantibodies. AIH has been considered to occur infrequently in SLE. We report two cases of AIH which simultaneously satisfied the criteria of SLE.(Korean J Hepatol 2003;9:231-235)

Neonatal Cholestasis

Sun-Young Jun, M.D. and Eunsil Yu, M.D.
신생아 간염(neonatal hepatitis)은 선천성 간외담도폐쇄증(congenital extrahepatic biliary atresia)과 함께 신생아 담즙정체증(neonatal cholestasis)의 중요한 원인이다. 드물지만 간내담관형성부전증 (paucity of intrahepatic bile duct)도 신생아의 담증정체증을 유발시키므로 감별이 필요한 질병이다. 선천성 간외담도폐쇄증은 Kasai 수술 등의 수술적 방법으로만 치료가 가능하고 수술 시기가 예후에 절대적으로 중요한 반면, 신생아 간염은 내과적 질환으로서 시험 개복을 하는 경우 만성 간질환으로 이행할 가능성이 증가하므로 질환의 감별이 매우 중요하다.1 간내담관형성부전증의 경우, 환아의 약 반수에서 특징적으로 얼굴과 골의 기형, 신체 및 정신 발육 지연, 폐동맥 형성부전 또는 협착 등이 동반되는 증후군형이므로 임상적으로 감별이 용이할 수도 있으나,1 비증후군인 경우에는 간생검으로 진단할 수 밖에 없다. 신생아 담즙정체증의 주요 원인 질환의 간생검 조직에서의 특징적인 조직학적 소견들을 정리해보고자 한다.

Hepatic Candidiasis in Patient with Acute Myelogenous Leukemia

Han Jun Gu , Kim Se Hyeong

Ultrastructure of Chronic Liver Diseases - Mitochondria and Mitochondrial Hepatopathies -

Jeong Gyu Won

Efficacy of Lamivudine in Patients with Hepatitis B e Antigen-Negative Chronic Liver Diseases
Background/Aims: Lamivudine therapy is effective in inhibiting HBV replications in patients with HBeAg-negative chronic liver disease. However, the sustained response rate appears to be particularly poor, because the vast majority of patients relapse soon after cessation of therapy. The aim of this study was to evaluate the efficacy of lamivudine, the breakthrough rate, and the relapse rate of discontinuing therapy after response in patients with HBeAg-negative chronic liver disease. Methods: Fifty-nine patients with HBeAg-negative chronic liver disease who have received lamivudine for at least 6 months, were studied. The mean duration of treatment was 14 months. Complete response was defined as undetectable serum HBV DNA by bDNA and normalization of ALT levels. Once HBV DNA disappearance and ALT normalization were observed, lamivudine therapy was continued for at least two additional months. The mean follow-up after cessation of treatment was 6 (1-22) months. Results: Fifty-six patients were undetectable HBV DNA. The cumulative HBV DNA loss rates at 3 months and 5 months were 90% and 95%, respectively. The ALT normalization was observed in 52 patients. The cumulative ALT normalization rates at 6 months and 10 months were 78% and 86%, respectively. The complete response was observed in 52 patients. The cumulative rates of complete response at 10 months and 18 months were 80% and 88%, respectively. A predictive factor for complete response was only the duration of lamivudine treatment. Virological breakthrough was observed in 5 (8.5%). Thirty-four patients stopped taking lamivudine after 7.7 (2-15) months of the additional therapy. Seventeen of those patients (50%) experienced relapse. The cumulative relapse rates at 3 months, 6 months and 10 months were 24%, 47%, and 66%, respectively. The only predictive factor for relapse was the duration of additional lamivudine treatment after response. Conclusions: Lamivudine was an effective treatment of HBeAg negative chronic liver disease. Relapse, however, was usually observed after cessation of lamivudine. Our results showed that long-term lamivudine therapy is required in order to decrease the high relapse rates in patients with HBeAg-negative chronic liver disease.(Korean J Hepatol 2003;9:69-78)

The Diagnostic Value of Serum Hyaluronic Acid, 7S Domain of Type IV Collagen and AST/ALT Ratio ...
Background/Aims: The prognosis of chronic liver disease is closely related to the development of hepatic fibrosis. Liver biopsy is the gold standard method to assess inflammatory activity and fibrosis stage, but this is associated with morbidity and mortality. This study aimed to evaluate the diagnostic value of serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis. Methods: This study included 100 patients with chronic hepatitis B and cirrhosis. Liver biopsy and histopathologic classification were done. Serum hyaluronic acid and 7S domain of type IV collagen were measured by one step sandwich binding protein assay and radioimmunoassay using polyclonal antibody to 7S domain of type IV collagen, respectively. Results: The serum concentrations of hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio in the cirrhosis group (139±98.4 ng/mL, 6.9±3.5 ng/mL, 1.6±1.5) were significantly higher (p<0.01) than those in the normal and fatty liver group (20.2±12.5 ng/mL, 3.5±0.5 ng/mL, 0.7±0.3), mild hepatitis group (32.3±52.7 ng/mL, 3.9±1.4 ng/mL, 0.7±0.4), and moderate to severe hepatitis group (68.2±72.3 ng/mL, 5.3±2.4 ng/mL, 0.8 type IV collagen and 0.62 for AST/ALT ratio, the sensitivities were 81.8%, 63.6%, 90.9% and specificities were 87.3%, 88.6%, 53.1% for discriminating cirrhosis (fibrosis score: 4) from the mild to severe fibrosis (fibrosis score: 0-3). Conclusions: Serum hyaluronic acid, 7S domain of type IV collagen and AST/ALT ratio measurement may be clinically useful as markers of hepatic fibrosis in chronic hepatitis B and cirrhosis.(Korean J Hepatol 2003;9:79-88)

Effects of Genetic Polymorphisms of Ethanol-Metabolizing Enzymes on Alcohol Drinking Behaviors
Background/Aims: Genetic variations of ethanol-metabolizing enzymes can affect alcohol drinking behavior. The aims of this study were to investigate and compare the distributions of these genetic polymorphisms between a healthy control group and a heavy drinker group which included an alcoholic liver cirrhosis group. Methods: Genotypes of ADH2, ALDH2, CYP2E1, and catalase were identified by polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from peripheral leukocytes in 42 healthy controls, 12 heavy drinkers, and 30 alcoholic liver cirrhosis patients. Results: 1) The genotype frequencies of ALDH2 (1＊1), ADH2 (1＊1), CYP2E1 (c1c1), and catalase1 (TT) were 69%, 55%, 38%, and 12%, respectively in healthy Korean males. 2) There was a significant difference in the distribution of the genetic polymorphism of ALDH2 between the control group and heavy drinker group (12 heavy drinkers and 30 alcoholic liver cirrhosis patients). The genotype frequency of ALDH2 mutant, ALDH2 (1＊2) and ALDH2 (2＊2) in the heavy drinker group (12%) was significantly lower than that in the control group (30%). 3) We didn`t find anyone with ALDH2 homozygote mutant (DD) in the heavy drinker group. 4) There was no significant difference in the distribution of genetic polymorphisms in ADH2, CYP2E1 and catalase1 between the two groups. Conclusions: These results suggest that the absence of ALDH2 mutant genotype is strongly related to heavy drinking behavior. We can not prove, however, any evidence that the polymorphisms of other ethanol-metabolizing enzymes are associated with the determination of alcohol-drinking behavior.(Korean J Hepatol 2003;9:89-97)

The Anaylsis of Mortality Rate According to CTP Score and MELD Score in Patients with Liver ...
Background/Aims: The Model for End-Stage Liver Disease (MELD) consists of serum bilirubin and creatinine levels, International Normalized Ratio (INR) for prothrombin time, and etiology of liver disease. The MELD score is a reliable measurement of mortality risk and is suitable for a disease severity index in patients with end-stage liver disease. We examined the validity of the MELD as a disease severity index for patients with end-stage liver disease. Methods: We investigated the 379 patients with liver cirrhosis hospitalized between January 1995 and May 2001. We retrospectively reviewed the hospital records to verify the diagnosis of cirrhosis and to collect exact patient information about their demographic data, portal hypertensive complications and laboratory data. The ability to classify patients with liver cirrhosis according to their risk of death was examined using the concordance c-statistic. Results: The MELD score performed well in predicting death within 3 months with a c-statistic of 0.73 with etiology and 0.71 without etiology. The significant clinical, laboratory variables on 3 month survival in patients with liver cirrhosis are serum bilirubin, ascites and hepatic encephalopathy. The addition of portal hypertensive complications to the MELD score did not improve the accuracy of the MELD score. Conclusions: The MELD score is a useful disease severity index for the patients with end-stage liver disease and provides reliable measurement of short term survival over a wide range of liver disease severity and diverse etiology.(Korean J Hepatol 2003;9:98-106)

The Correlation of Child-Pugh Score, PGA Index and MELD Score in the Patient with Liver ...

Byoung Sik Mun , Heok Soo Ahn , Deuk Soo Ahn , Seung Ok Lee
Background/Aims: To determine the treatment modalities and the prognosis of a patient with liver cirrhosis, quantitative estimation of liver function is important. We assessed the Child-Pugh score (CPS), the common method as a severity index for the cirrhosis, the Promthombin, -GT, and Apolipoprotein A1 (PGA) index and model for end-stage liver disease (MELD) score. The purpose of this study was to evaluate the correlation between these indices in the patients with cirrhosis only and hepatocellular carcinoma (PHC), according to underlying causes (HBV and alcohol). Methods: We reviewed medical records of 339 cirrhotic patients with/without hepatocellular carcinoma and divided patient groups by disease and underlying cause: cirrhosis caused by alcohol; LC-Al, cirrhosis caused by HBV; LC-B, hepatocellular carcinoma with cirrhosis caused by alcohol; HCC-Al, hepatocellular carcinoma with cirrhosis caused by HBV; HCC-B. We assessed the CPS, PGA index and MELD score and calculated the correlation coefficient between these scores. Results: Among the total of 339 patients, 201 patients were diagnosed on the liver cirrhosis only, and 138 patients on the hepatocellular carcinoma with cirrhosis. In each groups, mean score values were not significantly different in CPS, PGA index and MELD score. The correlation of CPS, PGA index and MELD score in all groups, except for the correlation of PGA index and MELD score in HCC-Al group, was significantly positive (p<0.05). Compared to correlation coefficients between three indices, the patients with cirrhosis only had higher tendencies than the patients with hepatocellular carcinoma. The patients by HBV had higher tendencies than by alcohol. Conclusions: The correlations between CPS, PGA index and MELD score showed significantly positive correlations in the patients with liver cirrhosis only and hepatocellular carcinoma with cirrhosis (except in HCC-Al group). The patients with cirrhosis only had higher correlation coefficients than the patients with PHC and the patients by HBV had higher than by alcohol.(Korean J Hepatol 2003;9:107-115)

Early Diagnosis and Improved Survival with Screening for Hepatocellular Carcinoma
Background/Aims: Screening for hepatocellular carcinoma (HCC) is a common practice in the endemic countries but its exact role has not been fully investigated. The purpose of this study was to determine whether screening can achieve early diagnosis and survival benefits. Methods: All HCC patients diagnosed at our hospital (September 1994∼April 2000) were enrolled; They were divided into two groups; a pre- screening group screened with alpha-fetoprotein and ultrasound for longer than 6 months before diagnosis and a non pre-screening group. We compared the tumor size, portal vein thrombosis, and stage at initial diagnosis and survival rate between the two groups. Results: A total of 247 patients were enrolled. 64 were in the non pre-screening group and 183 were in the non pre-screening group. The tumor size at initial diagnosis in the pre-screening group was smaller than in the non pre-screening group (2.6±2.0 cm vs. 5.7±4.1 cm, p<0.05). The percentages of patients with stage I, II, III, and IV were 42.2%, 20.3%, 14.1%, 23.4% in the pre-screening group and 8.7%, 19.7%, 36.6%, 35.0% in the non pre-screening group. A significantly higher proportion in the pre-screening group had earlier stage compared with the non pre-screening group (p<0.05). Portal vein thrombosis in the pre-screening group was noticed as significantly less than in the non pre-screening group (9.4% vs. 26.8%, p<0.05). Among Child A patients, the cumulative survival rate in the pre-screening group was significantly higher than in the non pre-screening group (1 year; 91.4% vs. 70.7%, 2 year; 71.5% vs. 59.9%, p<0.05). Conclusions: Screening with AFP and US is a useful tool for early diagnosis of HCC, especially with improved survival in Child A patients.(Korean J Hepatol 2003;9:116-123)

Suppression of Tumor Formation and Induction of Natural Killer Cell Activity in BALB/c Nude ...
Background/Aims: Immunogene therapy is extensively studied for a therapeutic modality of various cancers. This study was conducted to investigate the efficacy of immunogene therapy using the T-cell costimulatory molecule and human B7-1 (CD80, hB7-1) in an in vivo human hepatocellular carcinoma (HCC) model. Methods: The stable HCC cell line expressing hB7-1 gene was established using retroviral vector (Huh-7/hB7-1). Of fourteen BALB/c nude mice, 7 were subcutaneously injected with 2×10⁶Huh-7/hB7-1 cells, while the other 7 were injected with 2×10⁶Huh-7/mock cells as a control group. After the injection, the mice were observed weekly for three months for subcutaneous tumor formation. Assay for natural killer (NK) cell cytotoxicity and serum IFN-γ was performed at 1 and 2 weeks after inoculation. Results: In BALB/c nude mice inoculated with Huh-7/hB7-1 cells, no tumor growth was observed. BALB/c nude mice inoculated with Huh-7/hB7-1 cells showed significantly increased NK cell activities of splenocytes compared with those with Huh-7/mock cells. Serum IFN-γ was not measurable at 1 week, but significantly increased at 2 weeks after inoculation to the level of 470 pg/ml in BALB/c nude mice with Huh-7/mock cells and 521 pg/ml in BALB/c nude mice with Huh-7/hB7-1. Conclusions: Our results demonstrate the in vivo anti-tumor immunity and NK cell activation by transfer of hB7-1 gene into human HCC in xenogeneic BALB/c nude mice model. This approach may provide a tool for the development of immunogene therapies against human malignant tumors.(Korean J Hepatol 2003;9:124-134)

Development of a Method for the Immunological Measurement of Aspartate Aminotransferase with ...

Sunga Choi, Ph.D.1, Dong Joon Kim, M.D.2 and Eui Yul Choi, Ph.D.1,3
Background/Aims: For laboratory diagnostics in liver diseases, many enzymes have been used for the assessment of hepatocellular function. Among them, two transaminases, alanine and aspartate aminotransferase, have been regarded as the most sensitive indicators of hepatocellular damage. However, the enhanced enzyme activities of the enzymes do not exactly indicate or represent the cause and progression of diseases in the patients with liver disease. To overcome such limitations, immunological methods have been suggested as one of the alternatives for the replacement or supplement of the conventional enzymatic analysis. Methods: In the hope of developing a new assay system for measuring the AST concentration rather than its activity, we have developed a new assay using fluorescence labeled anti-AST monoclonal antibodies. Blood was obtained from a normal population of 234 patients and 43 liver disease patients. The linearity, limit of detection, and performance of the new assay system were tested and evaluated. The comparability of assay was examined with an ELISA and biochemical assays. Results: The linearity fell in the range of 0-1 mg/L of AST (R=0.995), and the analytical detection limit was 12㎍/L of AST. The mean recovery of the control was 102.4 % in a working range. The precision of the intra- and inter-assay in a range of 50-800 ㎍/L was CVs<7% and CVs<6%, respectively. In the normal population, the mean AST concentration was 35.5 ㎍/L. The mean AST concentration in patients with liver disease was 266.5 ㎍/L. The new assay system correlated well with an ELISA and biochemical assay for quantification of AST concentration (R=0.92 and 0.88, respectively; N=43). Conclusions: We have developed a new immunological assay using generated monoclonal antibodies to human cytosolic AST and used them for the development of a fluorescent assay measuring the enzyme mass. Cytosolic AST mass in sera could be measured reproducibly by the immunological method. In conclusion, this study has provided us with a new type of tool for an accurate measurement of the enzyme amount in circulation.(Korean J Hepatol 2003;9:135-144)

Activated stellate cells express the TRAIL receptor-2/death receptor-5 and undergo ...

Geun Youn Gwok , Jung Hwan Yoon
최근 간섬유화의 resolution phase에서 활성화된 간 성상세포(hepatic stellate cell)의 수가 줄어드는 기전으로 세포사멸(apoptosis)가 중요한 역할을 담당함이 알려지고 있다. 이러한 사실은 활성화된 간 성상세포가 휴지기에 있을 때보다 세포사멸을 일으키는 자극에 더 민감하다는 것을 암시한다. 이미 다른 종류의 세포들이 휴지 상태보다 활성화된 상태에서 TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)에 의한 세포사멸에 더 민감하다는 사실이 알려진 바 있기 때문에 본 연구자들은 이번 연구에서 점진적인 활성화 단계를 거치는 간 성상세포에서 단계별 TRAIL 사망 수용체(death receptor)의 발현과 TRAIL에 의한 세포 독성에 대한 민감도를 밝히고자 하였다. 자연적으로 불멸화된 인간 간 성상세포주인 LX-2 세포를 14일간 플라스틱 용기에서 배양하며 분석한 결과, 14일 후 간 성상세포 활성화의 지표인 α-smooth muscle actin (α-SMA)과 β-crystalline의 messenger RNA (mRNA)의 양이 각각 7배와 5배 증가하였으며, 같은 기간동안 TRAIL-R1/DR4와 TRAIL-R2/DR5 mRNA 발현은 각각 18배와 17.6배 증가하였다. 양적으로 보았을 때에는 TRAIL-R2/DR5의 발현이 TRAIL-R1/ DR4보다 103배 높았다. 아울러 TRAIL-R2/DR5 단백 발현과 TRAIL 유도 세포사멸에 대한 민감플라스틱 용기에서 활성화 과정을 거치는 동안 도에서도 동일한 양상의 변화가 관찰되었으며, 설치류의 간으로부터 일차배양한 간 성상세포 역시 유사한 변화를 보였다. 결론적으로 간 성상세포는 활성화되어감에 따라 TRAIL-R2/DR5 발현이 증가하고 TRAIL 유도 세포사멸에 민감해짐을 알 수 있었다. 따라서 임상적으로 TRAIL-R2/DR5 agonist가 생체 내에서 선택적으로 간 성상세포의 세포사멸을 유도하여 간섬유화를 줄이는데 유용하게 이용될 수 있을 것으로 기대된다.

Nonalcoholic Steatohepatitis

Sun Young Jun , Eun Dil Yu
지방간질환(fatty liver disease)은 그 원인에 따라 알코올성 지방간질환과 비알코올성 지방간질환으로 나누는데 최근에는 간 생검 조직검사에서 이 두 병을 진단하게 되는 경우가 모두 증가하고 있다. 임상적으로 분명한 알코올 섭취 병력이 있어야 두 진단의 감별이 가능하고 병리학적으로는 두 질환을 구별할 수 없다. 간 생검 조직검사에서 무엇보다 중요한 것은 지방간질환의 정도와 예후를 판단하는 것으로 만성간질환의 등급체계와 유사한 분류체계가 필요하지만 아직까지 국내에서는 이러한 체계가 정립되어 있지 않다. 다음 증례를 통해 지방간질환의 병리학적 진단에 적용할 수 있는 분류 또는 등급체계의 필요성을 살펴보고자 한다.

Biliary Hamartoma

Joon Koo Han , Se Hyung Kim

Ultrastructure of Chronic Liver Diseases ; The Cytoskeleton of the Hepatocyte

Kyu Won Chung

Natural YMDD Motif Mutations of HBV Polymerase in the Chronic Hepatitis B Virus Infected Patients
Background/Aims: Lamivudine, a nucleoside analogue has been widely used as an effective antiviral agent for the treatment of patients with chronic hepatitis B infection. However, the YMDD motif mutation of HBV polymerase resistant to lamivudine very frequently occurs after long-term use of lamivudine. It is well known that the mutation is selected by the lamivudine. We hypothesized that a few mutant strains of YMDD motif are present as quasispacies before the lamivudine treatment, are selected by the treatment, and breakthrough during treatment. We investigated the prevalence of the YMDD motif mutants in patients with chronic hepatitis B infection who had not been treated by antiviral agents before. Methods: The study included the serums of 40 patients with chronic heptitis B infection, which stored at -70℃. Thirty-four patients had chronic hepatitis and 6 patients had cirrhosis. Thirty-one patients were diagnosed by liver biopsy. The average age and range were 29 years and 13-57 years respectively. None had taken any antiviral agents before. To detect YMDD mutants, YVDD (M552V), and YIDD (M552I), we used direct sequencing and the restriction fragment length polymorphism (RFLP) method. Results: The YMDD mutant was detected by RFLP method in 7.5% (3/40) of the patients with chronic hepatitis B infection, in two patients with chronic hepatitis and one with cirrhosis. All were YMDD+ YIDD mutants. Conclusions: The YMDD motif mutation occurs spontaneously without antiviral therapy in patients with chronic hepatitis B infection.(Korean J Hepatol 2003;9:1-9)

The Effects of Tamoxifen on Human Hepatocelluar Carcinoma Cell Proliferation and Transforming ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: Tamoxifen has been tried in patients with hepatocellular carcinoma (HCC), however, its inhibitory mechanism remains unknown. In this study, we evaluated the effects of tamoxifen on HCC cell growth and the expression of transforming growth factor-β1 (TGF-β1) which had been known as an important cytokine in growth of HCC. Methods: Hep 3B cells were cultivated in estrogen free media with 0.1μM, 0.5μM, 1μM, 5μM, and 10μM of tamoxifen for 6 days. Viable cells were counted daily and the TGF-β1 concentrations in supernatant were measured by ELISA method. Results: The number of viable HCC cells increased rather significantly after the treatment of tamoxifen of lower concentration (0.1μM) compared with that of the control (2.59×10⁷ vs. 1.97×10⁷; p<0.05). As the concentration of treated tamoxifen was higher, the number of viable HCC cells became gradually less, resulting in the significant decrease of it at the highest concentration (10μM) compared with that of the control (1.40×10⁷ vs. 1.97×10⁷; p<0.05). TGF-β1 concentration in supernatant of tamoxifen-treated samples was significantly decreased compared with those of controls, regardless of the amount of treated tamoxifen. Conclusions: These results suggest that tamoxifen may suppress TGF-β1 expression to an extent, although it has different effects on the proliferation of HCC cells, at the various concentrations of this agent in vitro. Such effects of tamoxifen on TGF-β1 expression may inhibit the growth and progression of HCCs over-expressing TGF-β1 in vivo.(Korean J Hepatol 2002; 9:10-16)

The Clinical Usefulness of SPIO-MRI in Detection and Staging of Hepatocellular Carcinoma
Background/Aims: It is still unclear whether Super Paramagnetic Iron Oxide-Magnetic Resonance Imaging (SPIO-MRI) is a clinically useful imaging modality for patients with hepatocellular carcinoma (HCC). This study searched for the clinical usefulness and limitations of SPIO-MRI with respect to tumor detection capacity, false positive and negative rate, and early recurrence rate. Methods: From December 1999 to February 2001, 218 patients who were surgical candidates by 3-phase dynamic helical CT (3dHCT) were enrolled. We reviewed the medical records and radiologic findings, retrospectively, and postulated the post-operative pathologic findings and the early recurrences within 3 months as the standards for the true positive lesion. Results: The mean number of nodules detected by SPIO-MRI was significantly more numerous than that of 3dHCT (p<0.01). Modifications of treatment strategy due to the discordant findings between SPIO-MRI and 3dHCT for tumor resectability were observed in 22 (10.1%) out of 218 patients. Early recurrences were observed in 10 patients (7.8%). The false positive and negative rates of SPIO-MRI were 6.3% and 13.3%, respectively. Conclusions: We demonstrated that the tumor detection rate of SPIO-MRI was better than that of 3dHCT. Given the relatively acceptable false positive and negative rates, SPIO-MRI could be an appropriate preoperative imaging modality for patients with HCCs.(Korean J Hepatol 2002;9:17-24)

A Case of Auto-immune Hepatitis Associated with Primary Sjogren`s Syndrome
Auto-immune hepatitis is a chronic necroinflammatory liver disorder that is characterized by hypergammaglobulinemia, auto-antibodies in serum, and, on histological examination, the presence of periportal hepatitis. Although it can be associated with a number of other auto-immune diseases, Sj?gren’s syndrome is rarely associated with auto-immune hepatitis. We herein report an unusual case of auto-immune hepatitis associated with primary Sj?gren’s syndrome. A 39-year-old woman was admitted to our hospital due to jaundice. Laboratory data showed negative viral hepatitis marker, increased serum IgG level, positive anti- nuclear antibody, and an increased rheumatoid factor titer. The patient had no history of taking medications and alcohol. Based on characteristic clinical features, liver biopsy findings, positive Schirmer’s test, and salivary scintigraph, she was diagnosed as having auto-immune hepatitis and Sj?gren’s syndrome. The patient achieved complete remission with steroid monotherapy.(Korean J Hepatol 2003;9:25-30)

Mesenchymal Hamartoma of the Liver in Adults
Mesenchymal hamartoma of the liver (MHL) is a rare benign tumor usually found in childhood, especially during the first two years. MHL is extremely rare in adults. Most reported cases present with a slow growing abdominal mass. It is thought to be a developmental anomaly and consists of bile ducts, hepatocytes and mesenchymal tissue. We report a case of mesenchymal hamartoma of the liver in an adult male with a brief review of the literature.(Korean J Hepatol 2003;9:31-34)

Taehan Kan Hakhoe Chi (The Korean Journal of Hepatology) and Index Medicus (Medline/PubMed)

Dong Hoo Lee — Sat, 01 Jan 2000 00:00:01 +0100
It is our great pleasure to announce that the Taehan Kan Hakhoe Chi (The Korean Journal of Hepatology) was approved for listing, from 2002, in the Index Medicus, Medline/PubMed of the National Library of Medicine, NIH of USA. Herein, I review the searching tools employing a Medical Subject Heading (MeSH) such as liver disease and liver neoplasm or an author index for this Journal in the PubMed at a website. Of course, The Korean Journal of Hepatology should be continually striving to be upgraded. Dream comes true.(Korean J Hepatol 2003; 9:35-41)

Histologic Grading and Staging of Chronic Hepatitis -On the Basis of Standardized Guideline ...

Eun Sil Yu
우리 나라에는 여전히 B형 간염에 의한 만성간염 환자와 이와 관련된 종양의 발생빈도가 매우 높고 더욱이 C형 간염과 알코올성 간염의 발생 빈도도 증가하는 추세이어서 만성 간염의 정확한 진단은 더욱 중요해지고 있다. 만성 간염이란 다양한 원인에 의해 6개월 이상 간세포괴사와 염증이 계속되는 간의 염증성 질환으로서 임상 양상과 병리학적 소견이 매우 다양하고 이러한 다양한 병리학적 소견을 바탕으로 한 만성 간염의 분류는 병경과와 밀접한 관련이 있다는 것이 잘 알려져 있다. 그런데 Knodell 등1이 처음 간염활성의 점수화 체계를 제시한 후로 여러 등급체계가 발표되었고2-4 최근에는 International Association for the Study of the Liver에서 제안한 등급체계가 널리 사용되고 있다5 (Table 1). 그러나 이러한 등급체계는 만성 간염의 원인이 우리나라와 크게 다른 서구에서 만들어졌으며 주관적이고 재현성이 낮아 실제 사용할 때 문제점을 드러내고 있다. 우리나라에서는 1999년 대한병리학회 소화기병리연구회가 서구에서 사용되어 오던 만성 간염의 등급체계를 우리의 실정에 맞게 수정한 한국의 만성 간염 등급체계를 제안하였으며4(Table 2) 현재 간생검 조직에서 만성 간염을 진단할 때 실제로 사용하고 있다. 따라서 임상의사와 병리의사 사이의 원활한 의사 소통을 위하여 대표적인 만성 간염 예의 병리조직학적 소견을 통해 만성 간염의 조직학적 등급체계를 살펴보고자 한다.

Intraductal Intrahepatic Cholangiocarcinoama

Joon Koo Han , Young Jun Kim

Ultrastructure of Chronic Liver Diseases - Mallory Body of the Hepatocyte -

Kyu Won Chung

Relation of Apolipoprotein E Polymorphism to Clinically Diagnosed Fatty Liver Disease
Background/Aims: Apolipoprotein E (Apo E) is important in plasma lipid metabolism and is a component of several plasma lipoprotein-lipid particles. Three major Apo E isoforms are encoded by three common allelic forms, ε2, ε3, and ε4 at the APO E locus. The goal of this study was to examine the association between polymorphisms in the apolipoprotein E gene (APOE) and fatty liver disease. Methods: We examined the distribution of APOE alleles from 116 fatty liver patients and 50 controls in Korea. Results: The frequencies of APOE alleles in fatty liver patients were 6.5% in ε2, 85.7% in ε3 and 7.8% in ε4. The corresponding frequencies in control subjects were 4.0% in ε2, 91.0% in ε3 and 5.0% in ε4. There were no significant differences in the distribution of APOE genotypes between fatty liver patients and controls. APOE ε2 and ε4 allele frequencies in fatty liver patients were more than those in controls. However, there was no significant differences in APOE ε2 and ε4 allele frequencies. Conclusions: These results suggest that APOE alleles seem not to be directly associated with the pathogenesis of fatty liver disease. (Korean J Hepatol 2002;8:355-362)

Chemokine Receptor Expression of Hepatitis B Virus-Specific CD8+ Lymphocyte in Chronic B Viral ...

Sat, 01 Jan 2000 00:00:01 +0100
Background/Aims: The protective role of HBV-specific CD8⁺ cells is dependent on their ability to efficiently migrate to the infected liver, where they may exert an effector function. The migratory behavior of CD8⁺ cells is influenced by their expression of different chemokine receptors. This study was intended to analyse the pattern of chemokine receptor expression of HBV specific CD 8+ cells in chronic B viral infection. Methods: We analysed the CCR5 and CCR3 profile of HBV-specific CD8⁺ cells isolated from the blood and liver of patients with different patterns of HBV infection. Purified T cells were stained directly ex vivo, or after antigen-specific stimulation, using HBV peptide-specific HLA tetramers and monoclonal antibodies to CD8, CCR5 and CCR3, with analysis by flow cytometry. Results: In patients with chronic hepatitis B characterised by low levels of virus (serum HBV DNA <0.5pg/mL) and minimal liver inflammation, analysis of circulating and intrahepatic CD8⁺ cells demonstrated that liver infiltrating Tc18-27-specific cells were preferentially CCR5+ (up to 80% of HBV-specific CD8⁺ cells), in contrast to cells of the same specificity within the circulating compartment (up to 35% of HBV-specific CD8⁺ cells). Furthermore, CCR3 was expressed by about 10% of Tc18-27+ cells infiltrating the liver, but was absent from circulating cells. Following HBV-specific stimulation in vitro the CCR5 expression of circulating Tc18-27-specific cells was up-regulated, to levels found in liver infiltrating cells, whereas CCR3 expression was unchanged. Conclusions: The chemokine receptor profile of HBV-specific CD8⁺ cells is influenced by the anatomical site of these cells, and the clinical pattern of disease. The ability of circulating HBV-specific CD8⁺ cells of patients with low replicating virus to upregulate CCR5 suggests that these cells may respond to increases in virus replication by efficiently migrating into the infected liver. (Korean J Hepatol 2002;8:363-370)

Gene Expression Profile in Response to Hepatitis B Virus X Gene by Using an Adenoviral Vector

Heui Yun Joo, M.S., Kwang Hyub Han, M.D.*, Wang Shick Ryu, Ph.D
Background/Aims: Hepatitis B virus (HBV) is the etiological factor for hepatocellular carcinoma (HCC). Numerous evidence has indicated a link between chronic infection with HBV and the development of HCC. Among the four proteins encoded by HBV, Hepatitis B virus X gene(HBx), best characterized as a transcriptional transactivator, gained attention owing to its presumptive role in oncogenesis. Further, HBx has been shown to stimulate signal transduction pathways such as Ras-MAPK pathway, NF-꺢B, and Src kinase. The pleiotropic events caused by HBx may be the key to understanding the HBV-mediated oncogenicity. However, the specific roles of HBx in oncogenesis remain largely elusive. To explore the role of HBx in hepatocarcinogenesis, we examined the deregulation of host genes induced by HBx expression. Methods: HBx was ectopically expressed in HepG2 cells using a recombinant adenovirus to transiently express HBx. Gene expression profiling of HBx was conducted on cDNA microarrays that contained 1,028 cDNAs. Results: A number of oncogenes and genes that are involved in cell growth, DNA repair, cell cycle regulation, and cell motility were deregulated by HBx. Conclusions: Theses results suggest that HBx regulates transcription in a way that contributes to the proliferation of hepatocytes, a probable early event of HCC. (Korean J Hepatol 2002;8:371-380)

Relationship Between Core Gene Mutations of Hepatitis B Virus and Response to Alpha Interferon ...

Byung Chul Yoo , Hyung Joon Kim , Jae Hyuk Do , Sill Moo Park
Background/Aims: Treatment of chronic hepatitis B with interferon results in a sustained loss of hepatitis B virus DNA and hepatitis B e antigen (HBeAg) and remission of liver disease only in a proportion of cases. Recently, mutations of hepatitis B virus (HBV) core gene have been reported as being related to the failure of interferon treatment in chronic hepatitis B. This study investigated whether core gene mutations of HBV are related to non-response to interferon therapy and whether the recurrence of HbeAg and HBV DNA in initial responders to interferon therapy is associated with the emergence of HBV core gene mutants. Methods: The precore/core gene sequence was determined by polymerase chain reaction (PCR) and direct sequencing of PCR product in serum samples obtained before interferon treatment from 10 responders and 10 non-responders to interferon therapy. In addition, precore/core gene sequence was determined in serum samples obtained before interferon treatment and after recurrence from 10 patients who showed recurrence of HBeAg and HBV DNA after initial response to interferon therapy. Results: In samples from 10 responders, there were 7 missense mutations and 71 silent mutations. However, there were 43 missense mutations and 109 silent mutations in samples from 10 non-responders. In samples obtained before interferon treatment from the 10 patients who showed recurrence after initial response, 8 missense mutations and 74 silents mutations were found. The nucleotide sequences from the samples obtained after the recurrence showed 6 silent nucleotide substitutions compared with the sequences from the samples obtained before interferon treatment. Conclusions: Mutations in the core protein of HBV occur more frequently in non-responders than responders to interferon therapy of chronic hepatitis B and may be a factor responsible for the failure of interferon treatment. The recurrence of HBeAg and HBV-DNA in initial responders to interferon therapy is not associated with the emergence of the HBV core gene mutants. (Korean J Hepatol 2002;8:381-388)