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World J Gastroenterol. Oct 21, 2014; 20(39): 14142-14155
Published online Oct 21, 2014. doi: 10.3748/wjg.v20.i39.14142
Hepatitis B and liver transplantation: Molecular and clinical features that influence recurrence and outcome
Tahereh Ghaziani, Hossein Sendi, Saeid Shahraz, Philippe Zamor, Herbert L Bonkovsky
Tahereh Ghaziani, Department of Medicine School, Beth Israel-Deaconess Medical Center and Harvard Medical Liver Transplantation Institute, Boston, MA 02115, United States
Hossein Sendi, Departments of Medicine and Research, Carolinas HealthCare System, Charlotte, NC 28203, United States
Saeid Shahraz, Heller School of Social Policy and Management, Brandeis University, Waltham, MA 02454, United States
Philippe Zamor, Department of Medicine, Carolinas HealthCare System, Charlotte, NC 28204, United States
Herbert L Bonkovsky, The Liver-Biliary-Pancreatic Center, Department of Medicine, Carolinas HealthCare System, Charlotte, NC 28204, United States
Author contributions: All authors contributed equally to this work; all authos designed the review, wrote sections and edited the review.
Supported by A grant (No. R15 HL 117199) and contract No. U01 DK 065201 from the United States National Institutes of Health (to Bonkovsky HL) and institutional funds from Carolinas HealthCare System (to Sendi H) and Beth Israel Deaconess Medical Center (to Ghaziani T)
Correspondence to: Herbert L Bonkovsky, MD, Professor, Senior Adviser, The Liver-Biliary-Pancreatic Center, Department of Medicine, Carolinas HealthCare System, MMP1, 6th Floor, 1025 Morehead Medical Center Drive, Charlotte, NC 28204, United States. herbert.bonkovsky@carolinas.org
Telephone: +1-704-3557516 Fax: +1-704-3556998
Received: February 22, 2014
Revised: April 29, 2014
Accepted: May 25, 2014
Published online: October 21, 2014
Processing time: 240 Days and 3.6 Hours
Abstract

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, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.

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

Core tip: Hepatitis B viral (HBV) infection continues to be a major health problem world-wide. Recurrence of HBV following liver transplantation was a major problem in the 1980’s-1990’s, which led most insurers to refuse to cover costs of such transplants. This changed dramatically following the landmark demonstration that high-dose hepatitis B immune globulin (HBIG) could prevent recurrent infection. Recently, highly effective inhibitors of the HBV polymerase, with high barrier to resistance (entecavir, tenofovir) have become available, and they promise to decrease the need for HBIG and the costs and complexity of preventing recurrent HBV after liver transplantation.