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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2016; 22(1): 165-175
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.165
Prophylactic managements of hepatitis B viral infection in liver transplantation
Takashi Onoe, Hiroyuki Tahara, Yuka Tanaka, Hideki Ohdan
Takashi Onoe, Division of Applied Immunobiology, Institute for Clinical Research, National Hospital Organization, Kure Medical Center/Chugoku Cancer Center, Hiroshima 737-0023, Japan
Takashi Onoe, Hiroyuki Tahara, Yuka Tanaka, Hideki Ohdan, Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Author contributions: Onoe T performed the literature search, wrote the first draft of the manuscript, and approved the final version; Tahara H performed the literature search; Tahara H, Tanaka Y and Ohdan H edited the final draft of the manuscript and approved the final version.
Supported by A Grant-in-Aid for the Research of Hepatitis and BSE from the Japanese Ministry of Health, Labour and Welfare.
Conflict-of-interest statement: All authors declare no conflict of interests.
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: Dr. Takashi Onoe, MD, PhD, Head, Division of Applied Immunobiology, Institute for Clinical Research, National Hospital Organization, Kure Medical Center/Chugoku Cancer Center, 3-1 Aoyama-cho, Kure, Hiroshima 737-0023, Japan.
Telephone: +81-82-3223111 Fax: +81-82-3210478
Received: May 18, 2015
Peer-review started: May 20, 2015
First decision: August 26, 2015
Revised: November 11, 2015
Accepted: December 14, 2015
Article in press: December 14, 2015
Published online: January 7, 2016

Liver transplantation (LT) is a considerably effective treatment for patients with end-stage hepatitis B virus (HBV)-related liver disease. However, HBV infection often recurs after LT without prophylaxis. Since the 1990s, the treatment for preventing HBV reinfection after LT has greatly progressed with the introduction of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues (NAs), resulting in improved patient survival. The combination therapy consisting of high-dose HBIG and lamivudine is highly efficacious for preventing the recurrence of HBV infection after LT and became the standard prophylaxis for HBV recurrence. However, mainly due to the high cost of HBIG treatment, an alternative protocol for reducing the dose and duration of HBIG has been evaluated. Currently, combination therapy using low-dose HBIG and NAs is considered as the most efficacious and cost-effective prophylaxis for post-LT HBV reinfection. Recently, NA monotherapy and withdrawal of HBIG from combination therapy, along with the development of new, potent high genetic barrier NAs, have provided promising efficacy, especially for low-risk recipients. This review summarizes the prophylactic protocol and their efficacy including prophylaxis of de novo HBV infection from anti-HBc antibody-positive donors. In addition, challenging approaches such as discontinuation of all prophylaxis and active immunity through hepatitis B vaccination are discussed.

Keywords: Liver transplantation, Hepatitis B infection, Prophylaxis, Nucleos(t)ide analogue, Anti-hepatitis B immunoglobulin

Core tip: Combination therapy consisting of high-dose hepatitis B immunoglobulin (HBIG) and lamivudine has been the standard prophylaxis for hepatitis B virus recurrence after liver transplantation. Currently, after development of more potent high genetic barrier nucleos(t)ide analogues (hgbNAs), such as entecavir and tenofovir disoproxil fumarate, combination therapy using low-dose HBIG and hgbNA is considered as the most efficacious and cost-effective prophylaxis. In addition, monotherapy with hgbNAs and withdrawal of HBIG following combination therapy of HBIG and hgbNAs could be promising approaches, especially for low-risk patients and those receiving grafts from hepatitis B core antibody-positive donors. This review discusses those approaches including other challenging therapeutic options.