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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 14, 2016; 22(6): 1943-1952
Published online Feb 14, 2016. doi: 10.3748/wjg.v22.i6.1943
Hepatocellular carcinoma and hepatitis B surface protein
Yong-Wei Li, Feng-Cai Yang, Hui-Qiong Lu, Jiong-Shan Zhang
Yong-Wei Li, Jiong-Shan Zhang, Department of Traditional Chinese Medicine, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Feng-Cai Yang, Department of Medical Record Room, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Hui-Qiong Lu, Medical Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Author contributions: All authors equally contributed to the conception and design of the study, literature review, and analysis, critical revision, and editing of the paper; All authors approved the final version of the manuscript.
Supported by Science and Technology Planning Project of Guangdong Province, China, No. 2014A020212073.
Conflict-of-interest statement: The authors have 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: Dr. Yong-Wei Li, Department of Traditional Chinese Medicine, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. liyongwei22@163.com
Telephone: +86-20-85253028
Received: April 11, 2015
Peer-review started: April 13, 2015
First decision: June 26, 2015
Revised: July 27, 2015
Accepted: November 9, 2015
Article in press: December 1, 2015
Published online: February 14, 2016
Abstract

The tumorigenesis of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) has been widely studied. HBV envelope proteins are important for the structure and life cycle of HBV, and these proteins are useful for judging the natural disease course and guiding treatment. Truncated and mutated preS/S are produced by integrated viral sequences that are defective for replication. The preS/S mutants are considered “precursor lesions” of HCC. Different preS/S mutants induce various mechanisms of tumorigenesis, such as transactivation of transcription factors and an immune inflammatory response, thereby contributing to HCC. The preS2 mutants and type II “Ground Glass” hepatocytes represent novel biomarkers of HBV-associated HCC. The preS mutants may induce the unfolded protein response and endoplasmic reticulum stress-dependent and stress-independent pathways. Treatments to inhibit hepatitis B surface antigen (HBsAg) and damage secondary to HBsAg or the preS/S mutants include antivirals and antioxidants, such as silymarin, resveratrol, and glycyrrhizin acid. Methods for the prevention and treatment of HCC should be comprehensive.

Keywords: Hepatitis B surface protein, Hepatocellular carcinoma, PreS/S mutants, Endoplasmic reticulum stress, “Ground Glass” hepatocytes

Core tip: The tumorigenesis of hepatitis B virus-associated hepatocellular carcinoma (HCC) has been widely studied. The preS/S mutants are considered “precursor lesions” of HCC. Different preS/S mutants induce various mechanisms of tumorigenesis, such as transactivation and an inflammatory response. The preS2 mutants and type II “Ground Glass” hepatocytes represent novel biomarkers of HCC. The preS mutants may induce the unfolded protein response and endoplasmic reticulum stress-dependent and stress-independent pathways. Treatments to inhibit hepatitis B surface antigen (HBsAg) and damage secondary to HBsAg or the preS/S mutants include antivirals and antioxidants. Methods for the prevention and treatment of HCC should be comprehensive.