Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 18, 2015; 7(8): 1030-1040
Published online May 18, 2015. doi: 10.4254/wjh.v7.i8.1030
Current and future antiviral drug therapies of hepatitis B chronic infection
Lemonica Koumbi
Lemonica Koumbi, Hepatology and Gastroenterology Section, Department of Medicine, Imperial College London, London W2 1PG, United Kingdom
Author contributions: Koumbi L solely contributed to this work.
Conflict-of-interest: No conflict of interest.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lemonica Koumbi, Research Fellow, Hepatology and Gastroenterology Section, Department of Medicine, Imperial College London, St. Mary’s Campus, Norfolk Place, London W2 1PG, United Kingdom. lemonica.koumbi@gmail.com
Telephone: +44-207-5949022 Fax: +44-207-7069161
Received: August 28, 2014
Peer-review started: August 31, 2014
First decision: Novemeber 27, 2014
Revised: January 12, 2015
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: May 18, 2015
Processing time: 263 Days and 19.1 Hours
Abstract

Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host’s immune system. Currently the approved therapeutic regimens include pegylated-interferon (IFN)-α and monotherapy with five nucleos(t)ide analogues (NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

Keywords: Nucleos(t)ide analogues; Interferon-α; Drug resistance; Immunotherapy; Hepatitis B therapy

Core tip: Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem. Current therapeutic regimens include pegylated-interferon (IFN)-α and nucleos(t)ide analogues (NAs). Both treatments do not eradicate the virus and have numerous limitations. IFN therapy is of finite duration and has low response rates while long-term NA therapies have a high risk of drug resistance. The development of new therapeutic approaches is imperative. This review brings together current treatments and the ongoing research efforts on evaluating potential therapeutic strategies that target the suppression of HBV replication the restoration of the weak immune responses against HBV.