Prevention of HBV recurrence after liver transplant: A review

Abstract

Globally, hepatitis B virus (HBV) infection is recognized as a major risk factor for the development of hepatocellular carcino-ma, and HBV-induced liver failure is one of the leading indications for liver transplantation. Until about two decades ago, liver transplantation in patients with chronic HBV infection was a relative contraindication, due to high risk of viral replication with the use of immunosuppressants which could result in graft infection. In the 1990s, hepatitis B immunoglo-bulin (HBIg) use significantly reduced the risk of graft infection, improving outcomes of liver transplant in patients with chronic HBV infection. However, very high costs, especially with the need for long-term use, became a major concern. With the advent of nucleos(t)ide analogs (NAs), there was less need for high-dose, long-term HBIg use to prevent HBV recurrence. Lamivudine was initially used but resistance soon became a major issue. This was followed by more potent NAs, such as entecavir and tenofovir, emerging as the more preferred agents. Additionally, the use of these antiviral agents (HBIg and/or NAs) have made it possible to use the grafts from donors with positivity for hepatitis B core antibody, allowing for expansion of the donor pool. Nevertheless, there is no consensus on management protocols, which vary significantly amongst cen-ters. In this review, we appraise studies on management strategies used and the role of active vaccination in the prevention of HBV recurrence in post-liver transplant patients. Citation of this article: Nasir M, Wu GY. Prevention of HBV recurrence after liver transplant: A review. J Clin Transl Hepatol 2020;8(2):150–160. doi: 10.14218/JCTH.2020.00003. infection is the major risk factor for development of HCC, and has remained the leading indication for LT in Asian countries.2 Until the 1990s, HBV infection was considered a relative contra-indication to LT, due to high risk of graft infection and subse-quent liver failure as a result of post-transplant immunosuppression.3 Positivity for hepatitis B surface antigen (HBsAg) and presence of HBV DNA in liver biopsies after transplantation of HBV-naïve donor liver was considered to be diag-nostic for recurrence of HBV infection post-LT and was associated with poor long-term outcomes of those transplants.4 Over the past two decades, with the use of hepatitis B immunoglobulin (HBIg) and oral antivirals, a significant reduc-tion in post-transplant recurrence of HBV infection has been noted, allowing for successful LT in patients with chronic hepatitis B.5 The goal of antiviral therapy is the suppression of HBV DNA and preferably achievement of sustained virologic response (SVR). HBIg can be used to neutralize viral particles by binding to HBsAg, while nucleos(t)ide analogs (NAs) can be used to inhibit viral reverse transcriptase with consequent inhibition of HBV DNA replication. Combination of HBIg and NAs can also be used. However, there are no standardized protocols for the prevention of HBV recurrence after LT.5 In addition, the high cost of long-term HBIg use and resistance to certain NAs can limit their use, requiring alternate management strategies. Additionally, factors, such as presence of hepatitis B core antibody (HBcAb),6 HBsAg or HBV DNA at the time of LT introduce varying degrees of risk of recurrence post-LT. In this article, we review various regimens used for prevention of recurrence of HBV in post-LT patients.