Clinical and Molecular Hepatology

"HBV DNA"

Editorial

Viral hepatitis

Enhancing off-nucleos(t)ide analogue outcome predictions in chronic hepatitis B with time-varying hepatitis B core-related antigen: Chen-Te Huang, Tai-Chung Tseng; Clin Mol Hepatol 2024;30(2):154-156.
Published online February 22, 2024; DOI: https://doi.org/10.3350/cmh.2024.0120

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Optimizing off-treatment outcome predictions: The potential of time-varying HBcrAg and the need for more research
Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
Clinical and Molecular Hepatology.2024; 30(2): 276. CrossRef

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Letter to the Editor

Viral hepatitis

Letter regarding “Hepatitis B core-related antigen dynamics and risk of subsequent clinical relapses after nucleos(t)ide analog cessation”: Yun-Fan Liaw; Clin Mol Hepatol 2024;30(2):269-271.
Published online January 31, 2024; DOI: https://doi.org/10.3350/cmh.2024.0064

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Harnessing hepatitis B core-related antigen measurement to optimize posttreatment monitoring
Ying-Nan Tsai, Jia-Ling Wu, Yao-Chun Hsu
Clinical and Molecular Hepatology.2024; 30(2): 293. CrossRef

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Review

Viral hepatitis

New perspectives of biomarkers for the management of chronic hepatitis B: Chih-Lin Lin, Jia-Horng Kao; Clin Mol Hepatol 2016;22(4):423-431.
Published online December 25, 2016; DOI: https://doi.org/10.3350/cmh.2016.0069

Abstract
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With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.

Citations

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Original Articles

Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients: Jae Young Jang, Soung Won Jeong, Sung Ran Cheon, Sae Hwan Lee, Sang Gyune Kim, Young Koog Cheon, Young Seok Kim, Young Deok Cho, Hong Soo Kim, So Young Jin, Yun Soo Kim, Boo Sung Kim; Korean J Hepatol 2011;17(3):206-212.
Published online September 30, 2011; DOI: https://doi.org/10.3350/kjhep.2011.17.3.206

Abstract
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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.

Citations

Citations to this article as recorded by

Clinicopathological study of occult hepatitis B virus infection in hepatitis C virus-associated hepatocellular carcinoma
Mohamed A. El-Maksoud, Maha R. Habeeb, Hayam F. Ghazy, Manal M. Nomir, Hatem Elalfy, Sally Abed, Maysaa E.S. Zaki
European Journal of Gastroenterology & Hepatology.2019; 31(6): 716. CrossRef
Occult Hepatitis B Virus infection in a cohort of patients with chronic Hepatitis C
MA Amin, MI Naga, DA Algendy, AI El Badry, MM Fawzi
Archives of Hepatitis Research.2019; 5(1): 017. CrossRef
Occult Hepatitis B Infection in Hepatitis C Patients with Hematological Disorders
Nematollah Jonaidi-Jafari, Mohammad Saeid Rezaee-Zavareh, Javad Tavallaei-Nosratabadi, Reza Ajudani, Mahdi Ramezani-Binabaj, Hamidreza Karimi-Sari, Morteza Izadi, Reza Ranjbar, Seyyed Mohammad Miri, Seyed Moayed Alavian
Jundishapur Journal of Microbiology.2016;[Epub] CrossRef
Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection
Junhyeon Cho, Sang Soo Lee, Yun Suk Choi, Yejoo Jeon, Jung Wha Chung, Joo Yeong Baeg, Won Keun Si, Eun Sun Jang, Jin-Wook Kim, Sook-Hyang Jeong
World Journal of Gastroenterology.2016; 22(42): 9427. CrossRef
Update on occult hepatitis B virus infection
Manoochehr Makvandi
World Journal of Gastroenterology.2016; 22(39): 8720. CrossRef
Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients
H. E. Raouf, A. S. Yassin, S. A. Megahed, M. S. Ashour, T. M. Mansour
Journal of Viral Hepatitis.2015; 22(2): 103. CrossRef
Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers
Kyun-Hwan Kim, Hye-Young Chang, Jun Yong Park, Eun-Sook Park, Yong Kwang Park, Kwang-Hyub Han, Sang Hoon Ahn
Clinical and Molecular Hepatology.2014; 20(3): 251. CrossRef
Occult Hepatitis B Virus Infection in Chronic Hepatitis C
Jae Young Jang, Eui Ju Park
The Korean Journal of Gastroenterology.2013; 62(3): 154. CrossRef
The presence of hepatitis B core antibody is associated with more advanced liver disease in alcoholic patients with cirrhosis
Mingyuan Zhang, Ruihong Wu, Jing Jiang, Gerald Y. Minuk, Junqi Niu
Alcohol.2013; 47(7): 553. CrossRef
Definition, Diagnosis, and Prevalence of Occult Hepatitis B Virus Infection
Yun Soo Kim
The Korean Journal of Gastroenterology.2013; 62(3): 143. CrossRef
Detection of occult HBV infection by nested PCR assay among chronic hepatitis C patients with and without hepatocellular carcinoma
Shereen E. Taha, Soha A. El-Hady, Tamer M. Ahmed, Iman Z. Ahmed
Egyptian Journal of Medical Human Genetics.2013; 14(4): 353. CrossRef
Clinical Characteristics of Occult HBV Infection and Impact on Treatment Response in Patients with Chronic Hepatitis C
Sung Soo Byun, Jung Woo Shin, Myung Kwan Ko, Jung Min Hong, Kyung Hoon Kim, Mu Yeol Lee, Hye-Jeong Choi, Yoong Ki Jeong, Bo Ryung Park, Neung Hwa Park
Korean Journal of Medicine.2012; 83(6): 731. CrossRef

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Change of HBV DNA Level as a Predictor of HBeAg Loss after Lamivudine Treatment: Jae Kwon Jung, M.D., Chang Hyeong Lee, M.D., Eun Young Kim, M.D., Jin Tae Jung, M.D., Joon Hyuck Choi, M.D., Ji Min Han, M.D., Myoung In Jin, M.D., Ju Yeon Cho, M.D., Byung Seok Kim, M.D., Im Hee Shin, Ph.D.1; Korean J Hepatol 2007;13(4):513-520.
Published online December 20, 2007; DOI: https://doi.org/10.3350/kjhep.2007.13.4.513

Abstract
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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)

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The Effect of Long-term Lamivudine Therapy for Chronic Liver Disease due to Hepatitis B Virus: Kwang Hyub Han, M.D., Jin Suk Kim, M.D., Hyo Young Chung1, Sang Hoon Ahn, M.D., Yong Han Paik, M.D., Kwan Sik Lee, M.D., Chae Yoon Chon, M.D. and Young Myoung Moon, M.D.; Korean J Hepatol 1999;5(2):97-104.

Abstract
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Background/Aims
: We studied to evaluate the virological and biochemical responses to lamivudine and to detect YMDD mutants in patients who received long-term lamivudine therapy. Methods : We conducted a one-year trial of lamivudine in 45 Korean patients with chronic liver disease due to hepatitis B virus. The patients were treated with a single oral average dose of 100 mg of lamivudine every day for 12 months. Results : The suppression of serum HBV DNA was sustained in 77.8% of the patients and the normalization of serum ALT in 80%. The proportions of patients with HBeAg seroconversion were 25%. YMDD mutants were detected in 4 of 8 patients who showed sustained HBV DNA and serum ALT response (n=31) and in 3 of 8 patients who showed HBV DNA or serum ALT breakthrough (n=9). The response to lamivudine therapy in HBeAg-negative patients was excellent. Conclusion : Lamivudine therapy resulted in a significant virological and biochemical improvements and were well tolerated. But, YMDD mutants were detected during lamivudine therapy. (Korean J Hepatol 1999;5:97－104)

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Persistent Negative Anti-HBc in Chronic Hepatitis B Virus Carrier -Clinical Review, HBcAg and Nucleotide Sequence of It`s Epitope in HLA A2 Heterozygotes-: Jae Heung Kim,Haak Cheoul Kim; Korean J Hepatol 1999;5(2):105-115.

Abstract
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Background/Aims
: HBcAg is the most immunogenic HBV component and anti-HBc usually persists irrespective of ongoing liver disease or clearance of the virus in human. Therefore anti-HBc is considered as the most sensitive and occasionally the only marker of the HBV infection. Nevertheless, there are a few HBsAg carrier with persistent negative anti-HBc. The epitope which responds to HBcAg is recently defined in HLA A2 from acute viral hepatitis patient due to HBV. So we studied the clinical and laboratory features and nucleotide sequence of HBcAg corresponding to HLA A2 in the HBsAg carrier with persistent negative anti-HBc. Methods : The subject of these study consists of eight HBsAg chronic carriers with persistent negative anti-HBc. We followed up the clinical features and serological markers of HBV infection and determined the amount of humoral immunoglobulin, HBV DNA and HBcAg when we performed the HLA class I typing and sequencing analysis of core of HBV. Control cases were selected from 3 HLA A2 heterozygote cases with chronic HBsAg carriers with anti-HBc. Results : All subjects had the HBsAg persistently and good health conditions with normal ranges of aminotransferase and humoral immunoglobulin. One of them was converted to anti-HBc-positive during follow-up period. The level of HBV DNA in serum was higher than 1.2 pg/mL in 7 of 8 chronic HBV carriers. There was a trend of differences between chronic anti-HBc negative carriers and converted one case to anti-HBc positive in the serum of HBcAg and HBV DNA(p=0.06). But strong positive correlation was observed between the amount of HBcAg and HBV DNA in sera. The core portion of HBV was amplified in 4 of 6 HLA A2 heterozygotes by single PCR. When sequenced the PCR products of the above 4 chronic anti-HBc negative HBV carriers and 3 control cases directly, there were no significant difference in the nucleotide and amino acid sequence at the HBcAg epitope which corresopond to class 1 HLA A2. Conclusions : Our results show that persistent anti-HBc negative chronic HBV carriers may be caused by large amounts of HBV DNA and HBcAg in their sera and not by variants of HBV. These suggested that active viral replication was going on, but are undetectable by the available commercial tests due to binding with excessive amount of HBcAg in the HBV carriers with persistent negative anti-HBc. (Korean J Hepatol 1999;5:105－115)

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Emergence of YMDD Motif Mutant Hepatitis B Virus during Short-term Lamivudine Therapy: Yong Han Paik,Kwang Hyub Han,Hyo Young Chung,Chae Yoon Chun,Young Myoung Moon; Korean J Hepatol 1999;5(3):173-183.

Abstract
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Background/Aims
The emergence of lamivudine-resistant mutant hepatitis B virus (HBV), with aminoacid substitution in the YMDD motif of DNA polymerase, has been reported in the long-term lamivudine use group. However there is no report about the emergence of mutant viruses during the short-term lamivudine therapy. The
objective
of this study was to investigate the emergence of YMDD mutant HBV during short-term lamivudine therapy. Methods: We evaluated twenty-eight chronic hepatitis B patients who were HBeAg and HBV DNA positive and treated with lamivudine 100mg p.o. daily for 12 weeks. First, we investigated the emergence of YMDD mutants by nested polymerase chain reaction (PCR) method developed by Chayama et al in 19 patients who lost HBV DNA during lamivudine therapy but showed HBV DNA re-emergence 2 weeks after the end of therapy. Second, DNA subcloning and sequencing of HBV DNA polymerase including YMDD motif was undertaken in one patient's serial blood samples at 0, 8, 12 weeks to confirm the results of nested PCR. Results: YMDD motif mutation was detected in 17(90%) out of 19 patients at the end of therapy and the type of mutations were YIDD only. At the end of therapy, mutant was predominant in 5 patients, both mutant and wild type were similar in proportion in 3 patients, and wild type was predominant in 9 patients. When we carried out nested PCR serially with samples of 0, 2, 4, 8, 12, 14 weeks after initiation of therapy in 5 patients who were mutant predominant at 12 weeks, YIDD mutant began to be detected from 2 weeks in 4 patients and from 4 weeks in one patient. However, rapid turnover from mutant to wild type happened after the end of therapy, so only wild type was detected in 3 patients and wild type became predominant in 2 patients at 2 weeks after the end of therapy. All the sequencing results of serial blood samples in one patient were consistent with nested PCR data. Conclusions: The presence of YMDD motif HBV polymerase mutant may be possible before administration of lamivudine in Korean chronic hepatitis B patients. Nested PCR assay would be an useful method to detect YMDD mutant. (Korean J Hepatol 1999;5:173－183)

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A Prospective Study of Therapeutic Effect of 6 Months Trial with Lamivudine in Patients with Chronic Viral Hepatitis B: Chang Woo Gham,Soong Hwan Lee,Seung Woo Nam,Seung Woo Nam,Byung Joo Roh,Dong Hoo Lee; Korean J Hepatol 1999;5(4):282-290.

Abstract
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Background/Aims
The purpose of this study was to evaluate the effectiveness of lamivudine treatment in patients with chronic liver disease caused by chronic infection of hepatitis B virus (HBV). Methods: Thirty-five patients with chronic infection of HBV were included in this study who were diagnosed at Hanyang University Hospital from January 1998 to January 1999. They received 150mg of lamivudine per oral once daily for 6 months with follow-up of liver function test, serum HBV DNA and serologic markers for hepatitis B virus every two months. Lamivudine was well tolerated. Eight patients underwent liver biopsies before entering the study and follow-up biopsies were done at 5 patients. Results: Out of all 35 patients, chronic hepatitis patients histologically confirmed were 8, chronic hepatitis patients clinically diagnosed were 25 and liver cirrhosis patients clinically diagnosed were 2. The mean age was 35.7 years. Male-female ratio was 2.2:1. There was no hepatitis B surface antigen (HBsAg) negative seroconversion. The HBeAg loss rate was 26.9%(7/26) and HBeAg seroconversion rate was 10.7%(3/28) at the end of follow-up. Ten patients were anti-HBe positive prior to treatment, 3 of them became anti-HBe negative at the end of follow-up. Five patients underwent follow-up liver biopsies, in which histologic improvements were shown in 4 cases. Serum replicative HBV DNA by bDNA assay was decreased in all patients and HBV DNA was undetectable in 52.9%(9/17) at the end of treatment. Out of the 15 patients with abnormal alanine aminotransferase (ALT) levels at baseline, ALT level in 7 patients(46.7%) was normalized at treatment completion. Pretherapy ALT level was the only predictive factor for loss of HBeAg by stepwise logistic regression analysis(odds ratio : 1.0208) (95% Confidence Interval : 1.0023 ∼ 1.0396) (p value=0.0271). Conclusions: Lamivudine induced sustained suppression of HBV replication during treatment in all patients. In treating patients with lamivudine, who had chronic liver disease due to chronic infection of HBV, the improvement of liver function test and suppression of viral replication appeared early and was sustained during the 6months treatment. This, in turn, may induce histological improvement as well. Pretherapy ALT level was the only predictive determinant for HBeAg loss during lamivudine therapy, and that should be kept in mind in selecting patients for treatment. (Korean J Hepatol 1999;5:282－290)

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HBV DNA Levels, Aminotransferase and Histological Activity in Young Male Patients with HBeAg Positive Chronic Hepatitis B: Seung Chul Cho,Soong Hwan Lee,Joon Jae Shinn,Sung Hee Han,Byung Joo Roh,Joo Hyun Sohn,Dong Hoo Lee,Choon Suhk Kee; Korean J Hepatol 2002;8(1):44-51.

Abstract
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Background
/Aim: A significant correlation between HBV DNA and liver damage was found in precore mutant strains but there was no significant association between viral replication and liver damage in HBeAg positive patients. Laboratory tests are often requested to predict hepatitis activity (grade) and fibrosis (stage) in HBeAg positive chronic hepatitis B. We assessed ALT, AST, and HBV-branched DNA to find which is the best for predicting hepatitis activity and fibrosis. Methods: Routine biochemical liver function tests and HBV DNA in sera were assessed in 119 young patients positive with HBsAg and HBeAg. The mean age of patients was 21±2 years. All patients were male. By logistic regression analysis the relationships between laboratory data, hepatitis activity, fibrosis, or risk of chronic active hepatitis were analyzed. Results: There was a significant correlation between aminotransferase (AST, ALT) and hepatitis activity/ fibrosis. A significant inverse relationship between the HBV bDNA and hepatitis activity was demonstrated (Pearson's correlation coefficient: lobular activity,-0.305; porto-periportal activity, -0.410). But HBV bDNA was not correlated with severity of fibrosis. AST and HBV bDNA was the important test for predicting the more severe hepatitis activity (lobular activity and porto-periportal activity: score≥3, respectively) Conclusion: The higher AST, but the lower HBV bDNA, in sera shows the more severe hepatitis activity. AST and HBV bDNA could be helpful for assessing the hepatitis activity in young male patients with HBeAg positive chronic hepatitis B if proper reference values are used.(Korean J Hepatol 2002;8:44-51)

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The Clinical Significance of Quantitation of HBV DNA in Serum : Comparison of the Branched-DNA Assay with the Second-Generation Digene Hybrid Capture Assay and Long-term Observation: Eun Jung Jun, M.D., Joon-Yeol Han, M.D., Hwang Choi, M.D., U Im Chang, M.D., Tae Kyu Lee, M.D., Young Hwan Kim, M.D., Jin Il Kim, M.D., Soo Heon Park, M.D., Jae Kwang Kim, M.D., Kyu Won Chung, M.D. and Hee Sik Sun, M.D.; Korean J Hepatol 2002;8(2):157-166.

Abstract
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Backgrounds/Aims
Serum levels of hepatitis B virus (HBV) DNA are direct measures of viral replication in epatocytes. We compared branched- DNA assay (QuantiplexT M, bDNA) and Hybridization Capture II (HCII), and evaluated the clinical significance of HBV DNA quantitation in the natural course of HBV infection. Methods: We analyzed results of bDNA in 324 serum samples from 83 untreated male patients with chronic hepatitis B. Mean follow up period was 11.8 years. HCII was also performed in 157 arbitrarily selected samples. Results: HBV DNA levels measured with two assays were very similar (r²=0.893, p< 0.0001). HBV DNA detection rate of HCII was 6.4% higher than that of bDNA in HBeAg positive samples. HBV DNA detection rate was higher in cases with higher ALT . Among 73 patients with initial diagnosis of chronic hepatitis, 38 patients (52.1%) experienced progression to cirrhosis, and hepatocellular carcinoma (HCC) was developed in 9(12.3%). HCC was developed in 5 (50.0%) of 10 patients with initial diagnosis of cirrhosis. While HBeAg positive rates during chronic hepatitis, cirrhosis and HCC were 57.8%, 55.0% and 14.3%, respectively ( p=0.006), HBV DNA detection rates were 70.6%, 64.0% and 42.9%, respectively ( p=0.08). Especially in HCC, the discrepancy between HBeAg positive rate and HBV DNA detection rate may suggest the appearance of variants which cannot produce HBeAg. Conclusion: Both HCII and bDNA were similar HBV DNA quantitation assays for clinical use. HBV DNA level correlated with the severity of liver disease. Screening tests for HCC should be recommended in patients whose HBeAg is negative and have detectable HBV DNA. (Korean J Hepatol 2002;8:157-166)

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Serum ALT and HBV DNA Levels in Patients with HBeAg-Negative Chronic Hepatitis B: Kyung Hwan Kim, M.D., Il Hwan Na, M.D., Jae Moon Cha, M.D., Yong Ki Cho, M.D., Se Young Park, M.D., Hyoung Pil Kim, M.D., Chul Soo Song, M.D., Jeong Heo, M.D.1 and Mong Cho, M.D.1; Korean J Hepatol 2003;9(4):284-292.

Abstract
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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)