Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 14, 2018; 24(30): 3347-3360
Published online Aug 14, 2018. doi: 10.3748/wjg.v24.i30.3347
Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies
Izzet Mehmet Akcay, Seyma Katrinli, Kamil Ozdil, Gizem Dinler Doganay, Levent Doganay
Izzet Mehmet Akcay, Seyma Katrinli, Gizem Dinler Doganay, Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul 34469, Turkey
Kamil Ozdil, Levent Doganay, Department of Gastroenterology and Hepatology, Umraniye Teaching and Research Hospital, Istanbul 34764, Turkey
Author contributions: Akcay IM and Katrinli S researched the literature and wrote the article; Akcay IM, Katrinli S, Ozdil K, Doganay GD and Doganay L discussed the content; Akcay IM, Katrinli S, Doganay GD and Doganay L reviewed and edited the manuscript before submission; all authors approved the final version of the manuscript to be published.
Conflict-of-interest statement: We declare no potential conflict of interests.
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: Levent Doganay, MD, Associate Professor, Doctor, Department of Gastroenterology and Hepatology, Umraniye Teaching and Research Hospital, Umraniye, Istanbul 34764, Turkey.
Telephone: +90-216-6321818/1846 Fax: +90-216-6327124
Received: April 9, 2018
Peer-review started: April 10, 2018
First decision: May 16, 2018
Revised: May 29, 2018
Accepted: June 25, 2018
Article in press: June 25, 2018
Published online: August 14, 2018

The clinical outcome of Hepatitis B Virus (HBV) infection depends on the success or failure of the immune responses to HBV, and varies widely among individuals, ranging from asymptomatic self-limited infection, inactive carrier state, chronic hepatitis, cirrhosis, hepatocellular carcinoma, to liver failure. Genome-wide association studies (GWAS) identified key genetic factors influencing the pathogenesis of HBV-related traits. In this review, we discuss GWAS for persistence of HBV infection, antibody response to hepatitis B vaccine, and HBV-related advanced liver diseases. HBV persistence is associated with multiple genes with diverse roles in immune mechanisms. The strongest associations are found within the classical human leukocyte antigen (HLA) genes, highlighting the central role of antigen presentation in the immune response to HBV. Associated variants affect both epitope binding specificities and expression levels of HLA molecules. Several other susceptibility genes regulate the magnitude of adaptive immune responses, determining immunity vs tolerance. HBV persistence and nonresponse to vaccine share the same risk variants, implying overlapping genetic bases. On the other hand, the risk variants for HBV-related advanced liver diseases are largely different, suggesting different host-virus dynamics in acute vs chronic HBV infections. The findings of these GWAS are likely to pave the way for developing more effective preventive and therapeutic interventions by personalizing the management of HBV infection.

Keywords: Genome-wide association studies, Hepatitis B infection, Hepatocellular carcinoma, Cirrhosis, Antigen presentation, Immune response to hepatitis B virus

Core tip: Genome-wide association studies (GWAS) have proven to be very useful in uncovering the host genetic factors that influence the clinical outcomes of hepatitis B virus (HBV) infection. Both class I and class II human leukocyte antigen (HLA) genes were implicated in persistence of HBV infection; associated variants affected antigen-binding specificities and expression levels of HLA molecules. HBV persistence and vaccine nonresponse were associated with the same HLA-DP allotypes, suggesting a critical role for the surface antigen in HBV pathogenesis. These findings might be exploited for development of potent vaccines based on alternative epitopes. GWAS for HBV-related pathologies identified many other immune-related genes, and provided genetic markers to detect the individuals at high risk for HBV-related diseases.