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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): 126-144
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.126
Genetic variation of hepatitis B virus and its significance for pathogenesis
Zhen-Hua Zhang, Chun-Chen Wu, Xin-Wen Chen, Xu Li, Jun Li, Meng-Ji Lu
Zhen-Hua Zhang, Xu Li, Department of Infectious Diseases, the First Affiliated Hospital, Anhui Medical University, Hefei 230022, Anhui Province, China
Zhen-Hua Zhang, Jun Li, School of Pharmacy, Anhui Medical University, Hefei 230022, Anhui Province, China
Chun-Chen Wu, Xin-Wen Chen, State Key Lab of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, Hubei Province, China
Meng-Ji Lu, Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, 45122 Essen, Germany
Author contributions: Zhang ZH contributed to analysis and interpretation of data, and drafting the article; Wu CC contributed to drafting and revising the article for important intellectual content; Chen XW, Li X and Li J contributed to revising the article for important intellectual content; Lu MJ contributed to conception and design, analysis and interpretation of data, drafting and revising the article for important intellectual content.
Conflict-of-interest statement: The authors have declared that no potential conflict of interest exists.
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: Meng-Ji Lu, PhD, Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany. mengji.lu@uni-due.de
Telephone: +49-201-7233530 Fax: +49-201-7235929
Received: April 27, 2015
Peer-review started: May 4, 2015
First decision: August 26, 2015
Revised: September 25, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: January 7, 2016
Abstract

Hepatitis B virus (HBV) has a worldwide distribution and is endemic in many populations. Due to its unique life cycle which requires an error-prone reverse transcriptase for replication, it constantly evolves, resulting in tremendous genetic variation in the form of genotypes, sub-genotypes, and mutations. In recent years, there has been considerable research on the relationship between HBV genetic variation and HBV-related pathogenesis, which has profound implications in the natural history of HBV infection, viral detection, immune prevention, drug treatment and prognosis. In this review, we attempted to provide a brief account of the influence of HBV genotype on the pathogenesis of HBV infection and summarize our current knowledge on the effects of HBV mutations in different regions on HBV-associated pathogenesis, with an emphasis on mutations in the preS/S proteins in immune evasion, occult HBV infection and hepatocellular carcinoma (HCC), mutations in polymerase in relation to drug resistance, mutations in HBV core and e antigen in immune evasion, chronicalization of infection and hepatitis B-related acute-on-chronic liver failure, and finally mutations in HBV x proteins in HCC.

Keywords: Hepatitis B virus, Genotype, Variation, Pathogenesis

Core tip: Due to the unique life cycle of hepatitis B virus (HBV) which requires an error-prone reverse transcriptase for replication, it constantly evolves resulting in significant genetic variation in the form of genotype, sub-genotype, and mutations. A large number of publications on the relationship between HBV genetic variation and HBV-related pathogenesis have appeared in recent years. However, the progress in this field has not been reviewed. We have attempted to provide a brief account of the influence of HBV genotype and mutations in the different viral genome regions on HBV-associated pathogenesis. This review provides an overview for scientists working on HBV and related fields.