Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2019; 25(27): 3527-3537
Published online Jul 21, 2019. doi: 10.3748/wjg.v25.i27.3527
Immune suppression in chronic hepatitis B infection associated liver disease: A review
Tian-Yang Li, Yang Yang, Guo Zhou, Zheng-Kun Tu
Tian-Yang Li, Guo Zhou, Zheng-Kun Tu, Infectious Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, Guangdong Province, China
Yang Yang, Zheng-Kun Tu, Institute of Liver diseases, the First Hospital of Jilin University, Changchun 130061, Jilin Province, China
Author contributions: All authors equally contributed to this paper with the conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Supported by the National Natural Science Foundation of China, No. 81373143 and No. 81571535 to Tu ZK; Key Projects of Basic Research and Applied Basic Research in Universities of Guangdong Province, No. 2018KZDXM055 to Tu ZK.
Conflict-of-interest statement: No potential conflicts of interest. No financial support.
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/
Corresponding author: Zheng-Kun Tu, MD, Professor, Infectious Disease, Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang Middle Road, Guangzhou 510000, Guangdong Province, China. tuzhengkun@hotmail.com
Telephone: +86-20-34152635
Received: March 25, 2019
Peer-review started: March 26, 2019
First decision: April 16, 2019
Revised: April 29, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: July 21, 2019
Abstract

Hepatitis B virus (HBV) infection is one the leading risk factors for chronic hepatitis, liver fibrosis, cirrhosis and hepatocellular cancer (HCC), which are a major global health problem. A large number of clinical studies have shown that chronic HBV persistent infection causes the dysfunction of innate and adaptive immune response involving monocytes/macrophages, dendritic cells, natural killer (NK) cells, T cells. Among these immune cells, cell subsets with suppressive features have been recognized such as myeloid derived suppressive cells(MDSC), NK-reg, T-reg, which represent a critical regulatory system during liver fibrogenesis or tumourigenesis. However, the mechanisms that link HBV-induced immune dysfunction and HBV-related liver diseases are not understood. In this review we summarize the recent studies on innate and adaptive immune cell dysfunction in chronic HBV infection, liver fibrosis, cirrhosis, and HCC, and further discuss the potential mechanism of HBV-induced immunosuppressive cascade in HBV infection and consequences. It is hoped that this article will help ongoing research about the pathogenesis of HBV-related hepatic fibrosis and HBV-related HCC.

Keywords: Hepatitis B virus, Hepatocellular carcinoma, Liver fibrosis, Regulatory T cells, Regulatory natural killer cells, Dendritic cells, Monocytes

Core tip: We review that hepatitis B virus (HBV) induces suppressive function of the innate and adaptive immune cells in chronic HBV infection, and highlight that immune suppressive cascade contributes to the mechanism of HBV persistent infection. Further, we analyze the potential effects of HBV-induced immunosuppression in HBV-related fibrosis and hepatocellular carcinoma, thus providing underlying research directions for future studies into the pathogenesis of HBV-related disease.