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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 18, 2015; 7(8): 1086-1096
Published online May 18, 2015. doi: 10.4254/wjh.v7.i8.1086
Clinical relevance of hepatitis B virus variants
Shan Gao, Zhong-Ping Duan, Carla S Coffin
Shan Gao, Zhong-Ping Duan, Artificial Liver Center, Beijing You’an Hospital, Capital Medical University, Beijing 100000, China
Shan Gao, Carla S Coffin, Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Alberta T2N 4Z6, Canada
Author contributions: Gao S wrote the paper first draft; Duan ZP provided feedback and edited the manuscript; Coffin CS designed the paper, suggested topics for writing and literature to review and provided feedback on manuscript draft.
Supported by The National Science and Technology Key Project of China on “Major Infectious Diseases such as HIV/AIDS, Viral Hepatitis Prevention and Treatment”, No. 2013-ZX10002002-006 (Duan ZP); Speaker, advisory board and/or consulting fees from Boehringer ingelheim, GlaxoSmithKline, Janssen Pharmaceuticals, Bristol Myers Squibb, Roche Pharmaceuticals and Gilead Sciences (Coffin CS); The Canadian Institutes for Health Research (Coffin CS).
Conflict-of-interest: There are no disclosures relating to this body of work.
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: Carla S Coffin, MD, MSc, FRCPC, Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, 2500 University Drive Northwest, Calgary, Alberta T2N 4Z6, Canada. cscoffin@ucalgary.ca
Telephone: +1-403-5925049 Fax: +1-403-5925090
Received: November 28, 2014
Peer-review started: December 2, 2014
First decision: January 8, 2015
Revised: January 28, 2015
Accepted: February 10, 2015
Article in press: February 12, 2015
Published online: May 18, 2015
Abstract

The hepatitis B virus (HBV) is a global public health problem with more than 240 million people chronically infected worldwide, who are at risk for end-stage liver disease and hepatocellular carcinoma. There are an estimated 600000 deaths annually from complications of HBV-related liver disease. Antiviral therapy with nucleos/tide analogs (NA) targeting the HBV polymerase (P) can inhibit disease progression by long-term suppression of HBV replication. However, treatment may fail with first generation NA therapy due to the emergence of drug-resistant mutants, as well as incomplete medication adherence. The HBV replicates via an error-prone reverse transcriptase leading to quasispecies. Due to overlapping open reading frames mutations within the HBV P can cause concomitant changes in the HBV surface gene (S) and vice versa. HBV quasispecies diversity is associated with response to antiviral therapy, disease severity and long-term clinical outcomes. Specific mutants have been associated with antiviral drug resistance, immune escape, liver fibrosis development and tumorgenesis. An understanding of HBV variants and their clinical relevance may be important for monitoring chronic hepatitis B disease progression and treatment response. In this review, we will discuss HBV molecular virology, mechanism of variant development, and their potential clinical impact.

Keywords: Molecular virology, Genetic heterogeneity, Quasispecies, Drug resistance, Immune escape, Viral lymphotropism, Hepatitis B virus

Core tip: The hepatitis B virus (HBV) has significant genomic diversity and some HBV variants are associated with antiviral therapy response, vaccine escape, diagnostic failure, liver fibrosis progression and hepatocellular carcinoma development. Understanding HBV molecular epidemiology as well as the clinical and pathological relevence of HBV variants during different disease phases may enable more accurate risk-stratification of individual patients at risk for serious sequelae of chronic hepatitis B infection.