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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2018; 24(14): 1507-1520
Published online Apr 14, 2018. doi: 10.3748/wjg.v24.i14.1507
Hepatitis B virus pre-S/S variants in liver diseases
Bing-Fang Chen
Bing-Fang Chen, School of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan
Author contributions: Chen BF wrote the paper.
Supported by the grant from the National Science Council (NSC 96-2320-B-030-004-MY3), Executive Yuan, Taiwan.
Conflict-of-interest statement: No potential conflicts of interest.
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: Bing-Fang Chen, PhD, Professor, School of Medicine, Fu-Jen Catholic University, 510 Chung-Cheng Road, Hsin-Chuang Dist, New Taipei City 24205, Taiwan. nurs1018@mail.fju.edu.tw
Telephone: +886-2-29053428 Fax: +886-2-29052096
Received: March 8, 2018
Peer-review started: March 9, 2018
First decision: March 21, 2018
Revised: March 29, 2018
Accepted: March 31, 2018
Article in press: March 31, 2018
Published online: April 14, 2018
Processing time: 33 Days and 23.1 Hours
Abstract

Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Because of the spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B virus (HBV) genome evolves during the course of infection under the antiviral pressure of host immunity. The clinical significance of pre-S/S variants has become increasingly recognized in patients with chronic HBV infection. Pre-S/S variants are often identified in hepatitis B carriers with CH, LC, and HCC, which suggests that these naturally occurring pre-S/S variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. This paper reviews the function of the pre-S/S region along with recent findings related to the role of pre-S/S variants in liver diseases. According to the mutation type, five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, which results in liver diseases. Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. Additional investigations are required to explore the molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each stage of liver disease.

Keywords: Hepatitis B virus; Pre-S/S mutant; Pre-S deletion; Splice variant; spPS1; Chronic hepatitis; Liver cirrhosis; Hepatocellular carcinoma

Core tip: Naturally occurring hepatitis B virus (HBV) pre-S/S variants have been identified and associated with progressive liver diseases. In this review, the author discusses five pre-S/S variants: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are also discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, resulting in liver diseases. The exact pathogenesis of pre-S/S variants requires further investigation.