Retrospective Cohort Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2021; 27(37): 6262-6276
Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6262
Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families
Ai-Ru Hsieh, Cathy S J Fann, Hung-Chun Lin, Jennifer Tai, Sen-Yung Hsieh, Dar-In Tai
Ai-Ru Hsieh, Department of Statistics, Tamkang University, New Taipei City 25137, Taiwan
Cathy S J Fann, Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 11529, Taiwan
Hung-Chun Lin, Jennifer Tai, Sen-Yung Hsieh, Dar-In Tai, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan
Author contributions: Tai DI is the guarantor and designed the study; Hsieh AR and Fann CSJ participated in the statistical analysis and data interpretation; Lin HC, Tai J, Hsieh SY and Tai DI participated in the data acquisition; Fann CSJ revised the manuscript critically for important intellectual content.
Supported by Chang Gung Memorial Hospital, No. CMRPG3C0701; and National Science Council, No. NSC101-2314-B-182A-025-MY3 and No. MOST 107-2314-B-039-059.
Institutional review board statement: The study was approved by the institutional review board of Chang Gung Memorial Hospital, Taiwan (IRB 104-2596).
Informed consent statement: Written informed consent was obtained from all participants before the study. All experiments and data comparisons were carried out in compliance with relevant laws and guidelines, and in accord with the ethical standards of the Declaration of Helsinki.
Conflict-of-interest statement: The authors declare that they have no conflicting interests.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Dar-In Tai, MD, PhD, Professor, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, No. 5 Fuxing Street, Guishan District, Taoyuan 33305, Taiwan. tai48978@cgmh.org.tw
Received: April 8, 2021
Peer-review started: April 8, 2021
First decision: June 26, 2021
Revised: July 6, 2021
Accepted: September 1, 2021
Article in press: September 1, 2021
Published online: October 7, 2021
Processing time: 174 Days and 0.1 Hours
ARTICLE HIGHLIGHTS
Research background

Genome-wide association studies (GWASs) in Asian populations indicate that the HLA-DP and HLA-DQ loci are involved in the persistence of hepatitis B virus (HBV) infections. Persistent viral replication and inflammation are key influencers in HBV-related carcinogenesis.

Research motivation

HBV-related single nucleotide polymorphisms (SNPs) have been identified in east Asian populations but are uncommon in African populations. Different mechanisms may drive persistent infection in those regions.

Research objectives

We examined genetic and nongenetic factors associated with persistent HBV infection and viral load in families with hepatocellular carcinoma (HCC).

Research methods

HCC families were enrolled. Five HBV-related SNPs (rs477515, rs9272105, rs9276370, rs7756516, and rs9277535) were genotyped. Factors associated with persistent HBV infection and viral load were identified with the use of generalized estimating equations.

Research results

In the first-stage persistent HBV study, all SNPs except rs9272105 were associated with persistent infection. A significantly higher contribution of nongenetic than genetic factors (P < 0.001) to persistent HBV infection was found. In the second-stage viral load study, sex, relationship with index case, rs477515, rs9272105, and rs7756516 were associated with viral load. Receiver operating characteristic curve, and genetic and nongenetic factors had equal effects on viral load in the HCC family cohort (P = 0.3117).

Research conclusions

GWAS identified SNPs that have roles in persistent HBV infection and HBV viral loads in an HCC family cohort. Nongenetic factors were more important than genetic factors in persistent HBV infection but had equal contributions to HBV viral load. HBV-related SNPs resulting in high viral loads in parents may drive persistent infection in East Asian populations. The mechanism of persistent HBV infection-related SNPs involves a prolonged viral replication phase in East Asian adults.

Research perspectives

Termination of the HBV replication phase before pregnancy will be a therapeutic goal in East Asian countries.