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"Statin"

Research Letter

Hydrophilic and lipophilic statin and clinical outcomes in individuals with alcohol-associated liver disease
Pojsakorn Danpanichkul, Donghee Kim, Benjamin Nah, Karn Wijarnpreecha, Suthat Liangpunsakul
Clin Mol Hepatol 2025;31(3):e273-e276.
Published online May 27, 2025
DOI: https://doi.org/10.3350/cmh.2025.0474

Citations

Citations to this article as recorded by  Crossref logo
  • Association of documented social deprivation with cardiovascular and liver outcomes in alcohol-associated liver disease
    Pojsakorn Danpanichkul, Yanfang Pang, Andrew F. Ibrahim, Supapitch Sirimangklanurak, Allan Bueso, Daniel M. Simadibrata, Shu-Yen Chan, Karn Wijarnpreecha, Mazen Noureddin, Donghee Kim, Suthat Liangpunsakul
    Alcohol.2026; 132: 24.     CrossRef
  • Impact of Documented Social Vulnerability on Clinical Outcomes in Metabolic Dysfunction‐Associated Steatotic Liver Disease
    Pojsakorn Danpanichkul, Yanfang Pang, Maria Inggriani, Supapitch Sirimangklanurak, Matheus Souza, Ahmad Anouti, Andrew F. Ibrahim, Nikki Duong, Thomas G. Cotter, Thomas A. Kerr, Donghee Kim, Mazen Noureddin, Karn Wijarnpreecha
    Liver International.2026;[Epub]     CrossRef
  • Improved survival and reduced alcohol‐associated hepatitis risk with renin‐angiotensin‐aldosterone system inhibitors in alcohol‐associated liver disease
    Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Andrew F. Ibrahim, Primrose Tothanarungroj, Omar Al Ta'ani, Narathorn Kulthamrongsri, Kwanjit Duangsonk, Robert J. Wong, Daniel Q. Huang, Karn Wijarnpreecha, Mazen Noureddin, Suthat Liangpunsakul
    Alcohol, Clinical and Experimental Research.2026;[Epub]     CrossRef
  • Liver, Cardiovascular and Infectious Outcomes in Alcohol‐Associated Liver Disease With Cardiometabolic Risk Factors
    Pojsakorn Danpanichkul, Kwanjit Duangsonk, Yanfang Pang, Krittameth Rakwong, Peerapun Jit‐are‐roon, Phuuwadith Wattanachayakul, Thitiphan Srikulmontri, Benjamin Nah, Vincent L. Chen, Donghee Kim, Christos S. Mantzoros, Mazen Noureddin, Karn Wijarnpreecha
    Liver International.2026;[Epub]     CrossRef
  • Effect of varenicline on major adverse liver outcomes in alcohol‐associated liver disease: An exploratory analysis
    Pojsakorn Danpanichkul, Yanfang Pang, Donghee Kim, Thanathip Suenghataiphorn, Donghyun Ko, Andrew F. Ibrahim, Vitchapong Prasitsumrit, Kwanjit Duangsonk, Mazen Noureddin, Karn Wijarnpreecha, Suthat Liangpunsakul
    Alcohol, Clinical and Experimental Research.2025; 49(11): 2451.     CrossRef
  • 10,083 View
  • 61 Download
  • 5 Web of Science
  • Crossref

Editorial

Viral hepatitis

Citations

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  • Reply to correspondence on “Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy”
    Seren M. Gedallovich, Paul Y. Kwo
    Clinical and Molecular Hepatology.2024; 30(4): 1050.     CrossRef
  • Metformin in Antiviral Therapy: Evidence and Perspectives
    Iryna Halabitska, Pavlo Petakh, Oleh Lushchak, Iryna Kamyshna, Valentyn Oksenych, Oleksandr Kamyshnyi
    Viruses.2024; 16(12): 1938.     CrossRef
  • 7,562 View
  • 78 Download
  • 3 Web of Science
  • Crossref

Original Article

Viral hepatitis

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien Tsai, Chung-Feng Huang, Ming-Lun Yeh, Meng-Hsuan Hsieh, Hsing-Tao Kuo, Chao-Hung Hung, Kuo-Chih Tseng, Hsueh-Chou Lai, Cheng-Yuan Peng, Jing-Houng Wang, Jyh-Jou Chen, Pei-Lun Lee, Rong-Nan Chien, Chi-Chieh Yang, Gin-Ho Lo, Jia-Horng Kao, Chun-Jen Liu, Chen-Hua Liu, Sheng-Lei Yan, Chun-Yen Lin, Wei-Wen Su, Cheng-Hsin Chu, Chih-Jen Chen, Shui-Yi Tung, Chi‐Ming Tai, Chih-Wen Lin, Ching-Chu Lo, Pin-Nan Cheng, Yen-Cheng Chiu, Chia-Chi Wang, Jin-Shiung Cheng, Wei-Lun Tsai, Han-Chieh Lin, Yi-Hsiang Huang, Chi-Yi Chen, Jee-Fu Huang, Chia-Yen Dai, Wan-Long Chung, Ming-Jong Bair, Ming-Lung Yu, T-COACH Study Group
Clin Mol Hepatol 2024;30(3):468-486.
Published online April 19, 2024
DOI: https://doi.org/10.3350/cmh.2024.0038
Background/Aims
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Citations

Citations to this article as recorded by  Crossref logo
  • Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic
    Hiroyuki Suzuki, Naoto Fujiwara, Amit G. Singal, Thomas F. Baumert, Raymond T. Chung, Takumi Kawaguchi, Yujin Hoshida
    Hepatology.2026; 84(1): 292.     CrossRef
  • Response to comment on “High-normal and abnormal alanine transaminase levels linked to increased risk of hepatoma following treatment for chronic hepatitis C”
    Yen-Chun Chen, Ming-Lung Yu
    Journal of the Formosan Medical Association.2026; 125(4): 474.     CrossRef
  • Polypyridyl biguanide ruthenium complex induces photodynamic membrane damage, ferroptosis-like bacterial death, and “bubbling cell death”
    Jincan Chen, Jie Gao, Liang Hao, Qing Guo, Xiang Chen, Fengkai Cai, Zhiyi Li, Jia Zheng, Xufeng Zhu, Lanmei Chen
    Journal of Inorganic Biochemistry.2026; 274: 113110.     CrossRef
  • Exploiting tumor lineage features for precision cancer therapy
    Lois M. Kelly, Nina Fenouille, Kris C. Wood, Alexandre Puissant
    Trends in Cancer.2026; 12(4): 328.     CrossRef
  • Insulin resistance: mechanisms and therapeutic interventions
    Liuchunyang Yu, Jinxiu Qian, Xiaoyu Li, Meng Tian, Xiuyun Bai, Jue Yang, Rongjun Deng, Cheng Lu, Xiaojuan He, Aiping Lu, Yuanyan Liu
    Molecular Biomedicine.2026;[Epub]     CrossRef
  • Research Progress on the Molecular Mechanism of Metformin Regulating AMPK Signaling Pathway in Inhibiting Liver Cancer
    Hong Bin Zhang, Yan Yan, Jin Peng Pang, Meng Ting Kong, Qian Zhu
    OncoTargets and Therapy.2026; Volume 19: 1.     CrossRef
  • Ru(ii) complexes in antibacterial phototherapy: emerging strategies for combating bacterial infections
    Qipeng Yuan, Jiayan Huang, Kangqi Guan, Xia Zhou, Ying Xiong, Siping Wei, Lin Yang, Yao Jian
    Chemical Communications.2026; 62(33): 8340.     CrossRef
  • Metformin use and the risk of liver cancer in a Swedish population-based cohort study
    Yongying Huang, Giola Santoni, Ernesto Sparrelid, Shao-Hua Xie
    JNCI Cancer Spectrum.2026;[Epub]     CrossRef
  • Comment on “Evaluation of Factors Affecting Alpha Fetoprotein Levels in Patients With Hepatocellular Carcinoma in a Large Multicenter Cohort”
    Shitang Xu
    Journal of Gastroenterology and Hepatology.2026; 41(7): 2210.     CrossRef
  • Network toxicology-driven repurposing of metformin for hepatocellular carcinoma: insights from molecular docking and dynamics simulations
    Gong Wenqian, Zhang Wuguang, Zheng Kaifeng, Yuan Zuguo
    Journal of Molecular Modeling.2026;[Epub]     CrossRef
  • Beyond the Liver: A Comprehensive Review of Strategies to Prevent Hepatocellular Carcinoma
    Natchaya Polpichai, Sakditad Saowapa, Pojsakorn Danpanichkul, Shu-Yen Chan, Leandro Sierra, Johanna Blagoie, Chitchai Rattananukrom, Pimsiri Sripongpun, Apichat Kaewdech
    Journal of Clinical Medicine.2024; 13(22): 6770.     CrossRef
  • Metabolic Dysfunction-Associated Steatotic Liver Disease in Chronic Hepatitis C Virus Infection: From Basics to Clinical and Nutritional Management
    Karina Gonzalez-Aldaco, Luis A. Torres-Reyes, Claudia Ojeda-Granados, Leonardo Leal-Mercado, Sonia Roman, Arturo Panduro
    Clinics and Practice.2024; 14(6): 2542.     CrossRef
  • Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC)
    Davide Misceo, Gabriele Mocciaro, Simona D’Amore, Michele Vacca
    Nutrition & Metabolism.2024;[Epub]     CrossRef
  • 13,557 View
  • 229 Download
  • 20 Web of Science
  • Crossref

Reviews

Statin and aspirin for chemoprevention of hepatocellular carcinoma: Time to use or wait further?
Myung Ji Goh, Dong Hyun Sinn
Clin Mol Hepatol 2022;28(3):380-395.
Published online January 13, 2022
DOI: https://doi.org/10.3350/cmh.2021.0366
Preclinical studies highlighted potential therapeutic applications of aspirin and statins as anticancer agents based on their pleiotropic effects. Epidemiologic studies suggested the role of aspirin and statins in the chemoprevention of hepatocellular carcinoma (HCC). However, observational data is prone to bias, and no prospective randomized trials are currently available to assess the risks and benefits of statin or aspirin therapy for chemoprevention of HCC. It is therefore important for clinicians and researchers to be aware of the quality of current evidence regarding this issue. In this review, we summarize currently available evidence to assist clinicians with their decision to use statin or aspirin and provide information for further clinical investigations.

Citations

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  • Reconsidering statins in MASLD: beyond cardiovascular protection to multisystem benefit
    Xiao-Dong Zhou, Vincent Wai-Sun Wong, Ming-Hua Zheng
    Gut.2026; 75(1): 192.     CrossRef
  • Aspirin and hepatocellular carcinoma risk in metabolic dysfunction-associated steatotic liver disease: nationwide cohort study with genetic risk analysis
    Juhee Ahn, Moon Haeng Hur, Hyunjae Shin, Min Kyung Park, Sungho Won, Jeayeon Park, Yunmi Ko, Youngsu Park, Yun Bin Lee, Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Jung-Hwan Yoon, Yoon Jun Kim
    Clinical and Molecular Hepatology.2026; 32(1): 339.     CrossRef
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    Hepatoma Research.2026;[Epub]     CrossRef
  • Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis
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    Annals of Medicine.2025;[Epub]     CrossRef
  • Steatotic liver disease in chronic hepatitis C related hepatocellular carcinoma: Inflictor or bystander?: Correspondence to editorial on “Dynamic change of metabolic dysfunction-associated steatotic liver disease in chronic hepatitis C patients after vira
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    Clinical and Molecular Hepatology.2025; 31(1): e64.     CrossRef
  • Cancer Chemoprevention: An Exploration of the Efficacy and Potential of Various Materials (Synthetic and Natural)
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    Middle Eastern Cancer and Oncology Journal .2025; 1(2): 23.     CrossRef
  • Statin therapy for NAFLD: Molecular underpinnings of myopathic consequences and treatment strategies
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  • Aspirin Use and Risk of HCC and Gastrointestinal Bleeding in Patients With HBV‐Related Cirrhosis: A Landmark Analysis
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  • Aspirin reduces short-term mortality risk in critically ill patients with liver cirrhosis: a propensity-score matched retrospective analysis using the MIMIC-IV database
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  • The Impact of Statins on the Survival of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib or Lenvatinib
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    Frontiers in Pharmacology.2023;[Epub]     CrossRef
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  • Statin use and the risk of hepatocellular carcinoma among patients with chronic hepatitis B: an emulated target trial using longitudinal nationwide population cohort data
    Dong Hyun Sinn, Danbee Kang, Yewan Park, Hyunsoo Kim, Yun Soo Hong, Juhee Cho, Geum-Youn Gwak
    BMC Gastroenterology.2023;[Epub]     CrossRef
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  • 207 Download
  • 26 Web of Science
  • Crossref

Liver fibrosis, cirrhosis, and portal hypertension

Current knowledge about biomarkers of acute kidney injury in liver cirrhosis
Han Ah Lee, Yeon Seok Seo
Clin Mol Hepatol 2022;28(1):31-46.
Published online August 2, 2021
DOI: https://doi.org/10.3350/cmh.2021.0148
Acute kidney injury (AKI) is common in advanced cirrhosis. Prerenal azotemia, hepatorenal syndrome, and acute tubular necrosis are the main causes of AKI in patients with cirrhosis. Evaluation of renal function and differentiation between functional and structural kidney injury are important issues in the management of cirrhosis. However, AKI in cirrhosis exists as a complex clinical spectrum rather than concrete clinical entity. Based on current evidence, changes in serum creatinine (Cr) levels remain the most appropriate standard for defining AKI in cirrhosis. However, serum Cr has a limited role in assessing renal function in this population. This review examines previous studies that investigated the ability of recent biomarkers for AKI in cirrhosis from the perspective of earlier and accurate diagnosis, classification of AKI phenotype, and prediction of clinical outcomes. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin have been extensively studied in cirrhosis, and have facilitated improved diagnosis and prognosis prediction in patients with AKI. In addition, urine N-acetyl-β-D-glucosaminidase, interleukin 18, and kidney injury molecule 1 are other promising biomarkers for advanced cirrhosis. However, the clinical significance of these markers remains unclear because there are no cut-off values defining the normal range and differentiating phenotypes of AKI. In addition, AKI has been defined in terms of serum Cr, and renal biopsy—the gold standard—has not been carried out in most studies. Further discovery of innovate biomarkers and incorporation of various markers could improve the diagnosis and prognosis prediction of AKI, and will translate into meaningful improvements in patient outcomes.

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Original Articles

Hepatic neoplasm

The association of the serum levels of myostatin, follistatin, and interleukin-6 with sarcopenia, and their impacts on survival in patients with hepatocellular carcinoma
Kanghyug Choi, Hee Yoon Jang, Joong Mo Ahn, Sung Ho Hwang, Jung Wha Chung, Yun Suk Choi, Jin-Wook Kim, Eun Sun Jang, Gwang Hyeon Choi, Sook-Hyang Jeong
Clin Mol Hepatol 2020;26(4):492-505.
Published online July 10, 2020
DOI: https://doi.org/10.3350/cmh.2020.0005
Background/Aims
The role of serum myokine levels in sarcopenia and the outcome of hepatocellular carcinoma (HCC) patients are not clear. This study investigated the serum levels of myostatin, follistatin, and interleukin-6 (IL-6) in HCC patients and their association with sarcopenia and survival.
Methods
Using prospectively collected pretreatment samples from 238 HCC patients in a hospital from 2012 to 2015, the serum levels of 3 myokines were determined and compared to 50 samples from age and sex-matched healthy controls. Sarcopenia was evaluated using the psoas muscle index (PMI) measured at the third lumbar level in the computed tomography, and clinical data were collected until 2017.
Results
The median levels of the 3 myokines for the male and female HCC patients were as follow: myostatin (3,979.3 and 2,976.3 pg/mL), follistatin (2,118.5 and 2,174.6 pg/mL), and IL-6 (2.5 and 2.7 pg/mL), respectively. Those in the HCC patients were all significantly higher than in the healthy controls. In the HCC patient, the median PMI was 4.43 (males) and 2.17 cm2/m2 (females) with a sarcopenic prevalence of 56.4%. The serum levels of myostatin, IL-6 and follistatin in the HCC patients showed a positive, negative, and no correlation with PMI, respectively. The serum follistatin level was an independent factor for poor survival in HCC patients.
Conclusions
The serum levels of myostatin, follistatin, and IL-6 and their correlation with sarcopenia and survival were presented in HCC patients for the first time. The role of the serum follistatin level as a poor prognostic biomarker warrants further study.

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Serum cystatin C level is a useful marker for the evaluation of renal function in patients with cirrhotic ascites and normal serum creatinine levels
Dong Jin Kim, Hyun Seok Kang, Hyuk Soon Choi, Hye Jin Cho, Eun Sun Kim, Bora Keum, Hyonggin An, Ji Hoon Kim, Yeon Seok Seo, Yong Sik Kim, Hyung Joon Yim, Yoon Tae Jeen, Hong Sik Lee, Soon Ho Um, Chang Duck Kim, Ho Sang Ryu
Korean J Hepatol 2011;17(2):130-138.
Published online June 23, 2011
DOI: https://doi.org/10.3350/kjhep.2011.17.2.130
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-GFRMDRD, while it was not correlated with e-GFRC&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.

Citations

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Diagnostic value of cystatin C for predicting acute kidney injury in patients with liver cirrhosis
Mi Yeon Chung, Dae Won Jun, Su Ah Sung
Korean J Hepatol 2010;16(3):301-307.
Published online September 30, 2010
DOI: https://doi.org/10.3350/kjhep.2010.16.3.301
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.

Citations

Citations to this article as recorded by  Crossref logo
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Comparison of Somatostatin and Vasopressin in the Control of Acute Esophageal Variceal Hemorrhage : A Prospective Randomized Trial
Chae Yoon Chon, M.D., Jeong Il Jeong, M.D., Yong Han Paik, M.D., Chun Kyun Lee, M.D., Byung Hyun Choe, M.D., Kwan Sik Lee, M.D., Byung Soo Moon, M.D., Kwang-Hyub Han, M.D., Young Myoung Moon, M.D. and Dong Kee Kim, Ph.D.*
Korean J Hepatol 2000;6(4):468-473.
Background/Aims
Although endoscopic band ligation or injection sclerotherapy are the current standard therapies for bleeding esophageal varices, the best method for initial control is unclear. The aim of this prospective study was to compare the efficacy and toxicity of somatostatin and vasopressin in the management of esophageal variceal hemorrhage. Methods: From March, 1997 to September, 1998, 28 consecutive cirrhotic patients admitted to the Yonsei Medical Center because of active variceal bleeding were included in this trial. The patients were randomized to receive either somatostatin (15 patients) or vasopressin (13 patients) for 48 hours. Results: There were no significant differences between the two treatment groups in relation to Child's classification, amount of bleeding before randomization and units of blood transfused during therapy. Initial control of bleeding was achieved in 13 (86.7%) patients receiving somatostatin and in 10 (76.9%) of those treated with vasopressin. However, two patients in the somatostatin group and two in the vasopressin group bled again during treatment. Therefore complete control of bleeding during the 48 hours of therapy was achieved in 11 (73.4%) patients treated with somatostatin and in eight (61.5%) of those receiving vasopressin. Differences were observed in complications associated with each therapy. Vasopressin produced complications in four patients (chest pain in two, hypertension in one and hyponatremia-induced seizure in one) while somatostatin produced minor complication in one patient. Conclusions: This study suggests that somatostatin is efficacious in controlling acute hemorrhage from esophageal varices and has a lower risk of adverse effects than vasopressin.
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A Prospective Study Comparing the Efficacy of Early Administration of Terlipressin and Somatostatin for the Control of Acute Variceal Bleeding in Patients with Cirrhosis
Yeon Seok Seo, M.D., Soon Ho Um, M.D., Jong Jin Hyun, M.D., Youn Ho Kim, M.D., Sanghoon Park, M.D., Bo Ra Keum, M.D., Yong Sik Kim, M.D., Yoon Tae Jeen, M.D., Hong Sik Lee, M.D., Hoon Jai Chun, M.D., Sang Woo Lee, M.D., Jai Hyun Choi, M.D., Chang Duck Kim, M.D., and Ho Sang Ryu, M.D.
Korean J Hepatol 2006;12(3):373-384.
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.
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The Role of Angiostatin, Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9 and 12 in the Angiogenesis of Hepatocellular Carcinoma
Sook Kim, M.D.1, Ho Sung Park, M.D., Hyun Jin Son, M.D. and Woo Sung Moon, M.D.
Korean J Hepatol 2004;10(1):62-72.
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)
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