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Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome

World Journal of Gastroenterology 2014年第39期20卷 14142-14155页

作者： Tahereh Ghaziani hossein sendi Saeid Shahraz Philippe Zamor Herbert L Bonkovsky Department of Medicine School Beth Israel Deaconess Medical Center and Harvard Medical Liver Transplantation Institute Boston MA 02115 United States Departments of Medicine and Research Carolinas HealthCare System Charlotte NC 28203 United States Heller School of Social Policy and Management Brandeis University Waltham MA 02454 United States Department of Medicine Carolinas HealthCare System Charlotte NC 28204 United States The Liver-Biliary-Pancreatic Center Department of Medicine Carolinas HealthCare System Charlotte NC 28204 United States

Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of “hepatitis B virus AND liver transplantation”. We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, ce

关键词： Cirrhosis End-stage liver disease Entecavir Genetic variants Hepatocellular carcinoma Hepatitis B Interferon alpha Lamivudine Liver transplantation Tenofovir

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Legalon-SIL downregulates HCV core and NS5A in human hepatocytes expressing full-length HCV

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World Journal of Gastroenterology 2011年第13期17卷 1694-1700页

作者： Marjan Mehrab-Mohseni hossein sendi Nury Steuerwald Sriparna Ghosh Laura W Schrum Herbert L Bonkovsky The Liver-Biliary-Pancreatic Center Cannon Research Center Carolinas Medical Center Charlotte NC 28203 United States Department of Biology University of North Carolina at Charlotte Charlotte NC 28223 United States Department of Medicine University of North Carolina at Chapel Hill Chapel Hill NC United States

AIM: To determine the effect of Legalon-SIL (LS) on hepatitis C virus (HCV) core and NS5A expression and on heme oxygenase-1 (HMOX-1) and its transcriptional regulators in human hepatoma cells expressing full length HCV genotype 1b. METHODS: CON1 cells were treated with 50 μmol/L or 200 μmol/L LS. Cells were harvested after 2, 6 and 24 h. HCV RNA and protein levels were determined by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: HCV RNA (core and NS5A regions) wasdecreased after 6 h with LS 200 μmol/L (P < 0.05). Both 50 and 200 μmol/L LS decreased HCV RNA levels [core region (by 55% and 88%, respectively) and NS5A region (by 62% and 87%, respectively) after 24 h compared with vehicle (dimethyl sulphoxide) control (P < 0.01). Similarly HCV core and NS5A protein were decreased (by 85%, P < 0.01 and by 65%, P < 0.05, respectively) by LS 200 μmol/L. Bach1 and HMOX-1 RNA were also downregulated by LS treatment (P < 0.01), while Nrf2 protein was increased (P < 0.05).CONCLUSION: Our results demonstrate that treatment with LS downregulates HCV core and NS5A expression in CON1 cells which express full length HCV genotype 1b, and suggests that LS may prove to be a valuable alternative or adjunctive therapy for the treatment of HCV infection.

关键词： Hepatitis Hepatitis C virus Silymarin Silybin Genotype Huh7.5 CON1

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