Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Mar 27, 2018; 10(3): 352-370
Published online Mar 27, 2018. doi: 10.4254/wjh.v10.i3.352
Reactivation of hepatitis B after liver transplantation: Current knowledge, molecular mechanisms and implications in management
Ranjit Chauhan, Shilpa Lingala, Chiranjeevi Gadiparthi, Nivedita Lahiri, Smruti R Mohanty, Jian Wu, Tomasz I Michalak, Sanjaya K Satapathy
Ranjit Chauhan, Tomasz I Michalak, Molecular Virology and Hepatology Research Group, Division of BioMedical Sciences, Health Sciences Centre, Memorial University, St. John’s, NL A1B 3V6, Canada
Shilpa Lingala, Chiranjeevi Gadiparthi, Sanjaya K Satapathy, Division of Transplant Surgery, Methodist University Hospital Transplant Institute, University of Tennessee Health Sciences Center, Memphis, TN 38104, United States
Nivedita Lahiri, Division of Rheumatology, Immunology and Allergy, Brigham Women’s Hospital, Harvard Medical School, Boston, MA 02115, United States
Smruti R Mohanty, Division of Gastroenterology and Hepatobiliary Disease, New York-Presbyterian Brooklyn Methodist Hospital, Brooklyn, NY 11215, United States
Jian Wu, Department of Medical Microbiology, Key Laboratory of Molecular Virology, Fudan University School of Basic Medical Sciences, Shanghai 200032, China
Author contributions: Chauhan R, Lingala S and Gadiparthi C wrote the first draft; Chauhan R, Lingala S and Satapathy SK revised the manuscript with intellectual input from Lahiri N, Mohanty SR, Wu J and Michalak TI; all authors participated in additional discussions and revision of the manuscript.
Conflict-of-interest statement: All authors declare no potential conflicts of interest related to this manuscript. This manuscript is not supported by any grants/funding.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Sanjaya K Satapathy, MBBS, MD, DM, FACG, FASGE, AGAF, Associate Professor, Division of Transplant Surgery, Methodist University Hospital, University of Tennessee Health Sciences Center, 1211 Union Avenue, Suite #340, Memphis, TN 38104, United States.
Telephone: +1-901-5160929 Fax: +1-901-5168994
Received: October 16, 2017
Peer-review started: November 2, 2017
First decision: November 27, 2017
Revised: January 27, 2018
Accepted: February 9, 2018
Article in press: February 9, 2018
Published online: March 27, 2018

Chronic hepatitis B (CHB) is a major global health problem affecting an estimated 350 million people with more than 786000 individuals dying annually due to complications, such as cirrhosis, liver failure and hepatocellular carcinoma (HCC). Liver transplantation (LT) is considered gold standard for treatment of hepatitis B virus (HBV)-related liver failure and HCC. However, post-transplant viral reactivation can be detrimental to allograft function, leading to poor survival. Prophylaxis with high-dose hepatitis B immunoglobulin (HBIG) and anti-viral drugs have achieved remarkable progress in LT by suppressing viral replication and improving long-term survival. The combination of lamivudine (LAM) plus HBIG has been for many years the most widely used. However, life-long HBIG use is both cumbersome and costly, whereas long-term use of LAM results in resistant virus. Recently, in an effort to develop HBIG-free protocols, high potency nucleos(t)ide analogues, such as Entecavir or Tenofovir, have been tried either as monotherapy or in combination with low-dose HBIG with excellent results. Current focus is on novel antiviral targets, especially for covalently closed circular DNA (cccDNA), in an effort to eradicate HBV infection instead of viral suppression. However, there are several other molecular mechanisms through which HBV may reactivate and need equal attention. The purpose of this review is to address post-LT HBV reactivation, its risk factors, underlying molecular mechanisms, and recent advancements and future of anti-viral therapy.

Keywords: Hepatitis B virus, Liver transplantation, Reactivation, Hepatitis B immunoglobulin, Recurrence, Prophylaxis, Antivirals

Core tip: Aim of this review is to summarize the current concepts and management of hepatitis B after liver transplantation (LT). There are no clear guidelines regarding hepatitis B therapy after transplantation. Hepatitis B immunoglobulin (HBIG) is expensive and cumbersome to administer and there is no definite time point for discontinuation of HBIG after LT. Here we summarize the indications and duration of hepatitis B immunoglobulin and nucleoside analogs. This review also addresses key molecular mechanisms and the risk factors which are associated with hepatitis B virus reactivation post LT. This review provides up-to-date information not only for the liver transplant specialists but also for the virologists and scientists working in this field.