Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 18, 2015; 7(11): 1541-1552
Published online Jun 18, 2015. doi: 10.4254/wjh.v7.i11.1541
Current and future directions for treating hepatitis B virus infection
Akinobu Tawada, Tatsuo Kanda, Osamu Yokosuka
Akinobu Tawada, Tatsuo Kanda, Osamu Yokosuka, Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8677, Japan
Author contributions: Tawada A, Kanda T and Yokosuka O contributed to this paper.
Conflict-of-interest: Akinobu Tawada has no conflict of interest to declare. Tatsuo Kanda reports receiving lecture fees from Chugai Pharmaceutical, MSD, Tanabe-Mitsubishi, Daiichi-Sankyo, and Bristol-Myers Squibb, and Osamu Yokosuka reports receiving grant support from Chugai Pharmaceutical, Bayer, MSD, Daiichi-Sankyo, Tanabe-Mitsubishi, and Bristol-Myers Squibb.
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: Tatsuo Kanda, MD, PhD, Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan. kandat-cib@umin.ac.jp
Telephone: +81-43-2262086 Fax: +81-43-2262088
Received: January 10, 2015
Peer-review started: January 10, 2015
First decision: March 6, 2015
Revised: March 16, 2015
Accepted: April 28, 2015
Article in press: April 30, 2015
Published online: June 18, 2015
Abstract

Hepatitis B virus (HBV) persistently infects approximately 350 million people, and approximately 600000 liver-related deaths are observed per year worldwide. HBV infection is also one of the major risk factors for hepatocellular carcinoma (HCC). The persistence of serum hepatitis B e antigen (HBeAg) and high level of serum HBV DNA are thought to reflect a high HBV replication status in hepatocytes, causing cirrhosis, HCC and liver-related deaths. It has been reported that antiviral therapy, such as peginterferon and nucleos(t)ide analogues (NUCs), could suppress liver-related death by inhibiting the HBV DNA levels and inducing seroconversion from HBeAg to antibody to HBe antigen. Currently, peginterferon is widely used, but there are also several disadvantages in the use of peginterferon, such as various adverse events, the administration route and duration. It is difficult to predict the effects of treatment and interferon is contraindicated for the patients with advanced fibrosis of the liver and cirrhosis. With respect to NUCs, entecavir and tenofovir disoproxil fumarate are current the first-choice drugs. NUCs can be administered orally, and their anti-viral effects are stronger than that of peginterferon. However, because cessation of NUC administration leads to high levels of viral replication and causes severe hepatitis, they must be administered for a long time. On the other hand, the use of both interferon and NUCs cannot eliminate covalently closed circular DNA of HBV. In this review, we evaluate the natural course of chronic HBV infection and then provide an outline of these representative drugs, such as peginterferon, entecavir and tenofovir disoproxil fumarate.

Keywords: Hepatocellular carcinoma, Peginterferon, Nucleotide analogue, Chronic hepatitis B

Core tip: Chronic hepatitis B virus (HBV) infection is one of the major causes of hepatocellular carcinoma, which is a cancer with poor prognosis. We reviewed the natural course of HBV infection and current standard therapies for chronic HBV infection. Peginterferon and nucleos(t)ide analogues, such as entecavir and tenofovir disoproxil fumarate, have several drug-specific advantages and disadvantages. It is difficult to eliminate covalently closed circular DNA of HBV with these current standard therapies. Further improvements of the therapeutic options for HBV infections should be needed.