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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): 145-154
Published online Jan 7, 2016. doi: 10.3748/wjg.v22.i1.145
Overview of hepatitis B virus mutations and their implications in the management of infection
Patrizia Caligiuri, Rita Cerruti, Giancarlo Icardi, Bianca Bruzzone
Patrizia Caligiuri, Giancarlo Icardi, Department of Health Sciences, University of Genoa, 16132 Genoa, Italy
Rita Cerruti, Giancarlo Icardi, Bianca Bruzzone, Hygiene Unit, I.R.C.C.S. A.O.U. San Martino-IST, 16132 Genoa, Italy
Author contributions: Caligiuri P, Cerruti R, Icardi G and Bruzzone B analyzed the literature and wrote this review.
Conflict-of-interest statement: The authors have no conflict of interest regarding this review.
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:
Correspondence to: Dr. Patrizia Caligiuri, Department of Health Sciences, University of Genoa, Largo R. Benzi 10, 16132 Genoa, Italy.
Telephone: +39-10-5600591 Fax: +39-10-5600912
Received: May 29, 2015
Peer-review started: June 3, 2015
First decision: July 14, 2015
Revised: August 19, 2015
Accepted: December 1, 2015
Article in press: December 1, 2015
Published online: January 7, 2016

Hepatitis B virus (HBV) affects approximately two billion people worldwide and more than 240 million people in the world are currently chronic carrier that could develop serious complications in the future, like liver cirrhosis and hepatocellular carcinoma. Although an extended HBV immunization program is being carried out since the early ‘80s, representing effective preventive measure, leading to a dramatic reduction of HBV hepatitis incidence, globally HBV infection still represents a major public health problem. The HBV virus is a DNA virus belongs to the Hepadnaviridae family. The HBV-DNA is a circular, partial double strand genome. All coding information is on the minus DNA strand and it is organized into four open reading frames. Despite hepatitis B virus is a DNA virus, it has a high mutation rate due to its replicative strategy, that leads to the production of many non-identical variants at each cycle of replication. In fact, it contains a polymerase without the proofreading activity, and uses an RNA intermediate (pgRNA) during its replication, so error frequencies are comparable to those seen in retroviruses and other RNA viruses rather than in more stable DNA viruses. Due to the low fidelity of the polymerase, the high replication rate and the overlapping reading frames, mutations occur throughout the genome and they have been identified both in the structural and not structural gene. The arise of mutations being to develop of a whole of viral variants called “quasi-species” and the prevalent population, which favors virus replication, was selected by viral fitness, host’s immune pressure and external pressure, i.e., vaccination or antiviral therapy. Naturally occurring mutations were found both in acute and chronic subjects. In the present review we examine and discuss the most recent available data about HBV genetic variability and its significance.

Keywords: Hepatitis B virus, Mutations, Open reading frames, Molecular biology tools, Liver disease

Core tip: Hepatitis B virus (HBV) is a global health problem, with almost 2 billion infected persons, many of whom deemed to develop chronic carrier state and eventually die from cirrhosis or liver cancer. Unlike in other DNA viruses, its high mutation rate and replicative capability arise considerable genetic variability, recently analyzed by molecular biology tools. HBV mutations occur in all four overlapping open reading frames encoding viral polymerase, surface antigen, core and X protein. Understanding the correlation between mutations and liver disease progression is crucial for an effective clinical management in HBV patients with resistance to antiviral drugs, hepatitis B surface antigen escape mutant, “occult” hepatitis and hepatocellular carcinoma.