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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 28, 2015; 7(27): 2729-2739
Published online Nov 28, 2015. doi: 10.4254/wjh.v7.i27.2729
Clinical significance of hepatitis B surface antigen mutants
Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Caterina Sagnelli, Evangelista Sagnelli
Nicola Coppola, Lorenzo Onorato, Carmine Minichini, Giovanni Di Caprio, Mario Starace, Evangelista Sagnelli, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, 80131 Naples, Italy
Caterina Sagnelli, Department of Clinical and Experimental Medicine and Surgery “F. Magrassi e A. Lanzara”, Second University of Naples, 80131 Naples, Italy
Author contributions: Coppola N has contributed to conception of the paper and draft the article; Onorato L has analyzed the role of HBsAg mutants associated with HCC development; Minichini C has analyzed the HBV virology and HBsAg structure; Di Caprio G has analyzed the role of HBsAg mutants associated with immune escape; Starace M has analyzed the HBV virology and HBsAg structure; Sagnelli C has analyzed the role of HBsAg mutants associated with failed HBsAg detection; Sagnelli E has contributed to conception of the paper and draft the article.
Conflict-of-interest statement: The authors declare no conflicts of interest regarding this manuscript.
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: Nicola Coppola, MD, PhD, Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Via: L. Armanni 5, 80131 Naples, Italy. nicola.coppola@unina2.it
Telephone: +39-8-15666719 Fax: +39-8-15666013
Received: June 30, 2015
Peer-review started: June 30, 2015
First decision: September 18, 2015
Revised: September 27, 2015
Accepted: November 13, 2015
Article in press: November 17, 2015
Published online: November 28, 2015
Processing time: 151 Days and 16.7 Hours
Abstract

Hepatitis B virus (HBV) infection is a major public health problem in many countries, with nearly 300 million people worldwide carrying HBV chronic infection and over 1 million deaths per year due to cirrhosis and liver cancer. Several hepatitis B surface antigen (HBsAg) mutations have been described, most frequently due to a single amino acid substitution and seldom to a nucleotide deletion. The majority of mutations are located in the S region, but they have also been found in the pre-S1 and pre-S2 regions. Single amino acid substitutions in the major hydrophilic region of HBsAg, called the “a” determinant, have been associated with immune escape and the consequent failure of HBV vaccination and HBsAg detection, whereas deletions in the pre-S1 or pre-S2 regions have been associated with the development of hepatocellular carcinoma. This review article will focus on the HBsAg mutants and their biological and clinical implications.

Keywords: Hepatitis B virus infection; Vaccine escape; Immune escape hepatocellular carcinoma; Hepatitis B surface antigen mutants

Core tip: Antibodies to the hepatitis B surface antigen (HBsAg) produced in response to hepatitis B virus infection or vaccination and those used in diagnostic assays to detect this antigen in serum are both directed against the ‘‘a’’ determinant region, common to all subtypes of the virus. Mutations occurring on the loops of the “a” determinant may be responsible for the lack of protection in immunized patients and in those individuals receiving hepatitis B immune globulin or for failed detection of HBsAg using commercial diagnostic assays. There is growing evidence in the last decade of the association between HBsAg mutations and the development of hepatocellular carcinoma (HCC), suggesting that the pre-S1 or pre-S2 large deletions are those prevalently associated with the development of HCC. This review article will focus on the clinical impact of the various HBsAg mutants.