Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2021; 12(11): 1928-1941
Published online Nov 15, 2021. doi: 10.4239/wjd.v12.i11.1928
Role of hepatitis A virus in diabetes mellitus
James Lin, Horng-Yih Ou, Rudruidee Karnchanasorn, Raynald Samoa, Lee-Ming Chuang, Ken C Chiu
James Lin, Department of Gastroenterology, City of Hope National Medical Center, Duarte, CA 91010, United States
Horng-Yih Ou, Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital, Tainan 700, Taiwan
Rudruidee Karnchanasorn, Division of Endocrinology, Metabolism and Genetics, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
Raynald Samoa, Department of Clinical Diabetes, Endocrinology, and Metabolism, Diabetes and Metabolism Research Institute, City of Hope National Medical Center, Duarte, CA 91010, United States
Raynald Samoa, Ken C Chiu, Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502, United States of America
Lee-Ming Chuang, Department of Internal Medicine, National Taiwan University Hospital, Taipei 102, Taiwan
Lee-Ming Chuang, Graduate Institute of Preventive Medicine, School of Public Health, Taipei 102, Taiwan
Author contributions: Chiu KC, Lin J, and Chuang L-M conceived and designed the study; Karnchanasorn R and Ou HY obtained data under the direction of Chiu KC, Lin J, and Chuang LM; Chiu KC, and Samoa R reviewed the integrity of data; All authors had full access to all the data in the study; Karnchanasorn R, Chiu KC, and Chuang LM performed statistical analyses and interpreted data; Chiu KC and Lin J drafted the paper; All authors revised the paper for important intellectual content; Chiu KC, and Samoa R provided administrative, technical, and material support; Chiu KC is the guarantor of this work and takes responsibility for the integrity of the data and accuracy of the data analysis.
Institutional review board statement: The study was reviewed and approved by the NCHS Research Ethics Review Board, Centers for Disease Control and Prevention.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: Data is available at the NHANES website https://wwwn.cdc.gov/nchs/nhanes/Default.aspx.
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: Ken C Chiu, FACE, FCCP, MD, Professor, Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502, United States. kenchiumd@gmail.com
Received: April 28, 2021
Peer-review started: April 28, 2021
First decision: June 16, 2021
Revised: June 23, 2021
Accepted: October 27, 2021
Article in press: October 27, 2021
Published online: November 15, 2021
Processing time: 200 Days and 16 Hours
ARTICLE HIGHLIGHTS
Research background

The liver plays an important role in glucose hemostasis. Hepatitis C infection increases the risk of diabetes. Thus, other liver infection could also play a role in the pathogenesis of diabetes.

Research motivation

This study is to dissect the relationship between hepatitis A and diabetes.

Research objectives

The objective of this study is to investigate the interaction between hepatitis A and diabetes through hypothesis testing in a representative adult cohort of the United States.

Research methods

The information on hepatitis A vaccination history, hepatitis A antibody status, and diabetes status were obtained from the participants in the National Health and Nutrition Examination Survey 2005-2012. Hepatitis A infection was defined as the presence of hepatitis A antibody without hepatitis A vaccination. Hepatitis A vaccination was defined as the presence of hepatitis A vaccination, regardless hepatitis A antibody status. Successful hepatitis A immunization was defined as the presence of both hepatitis A vaccination and hepatitis A antibody. A stepwise hypothesis testing approach was used to dissect the interaction between hepatitis A and diabetes and the sensitivity tests based on the different definitions of diabetes were used to confirm the results.

Research results

Diabetes risk was increased in the participants with hepatitis A infection, suggesting a causal relationship between hepatitis A infection and diabetes. However, hepatitis A vaccination and also successful hepatitis A immunization did not reduce the risk of diabetes, excluding hepatitis A infection as a cause of diabetes. In non-hepatitis A vaccinated participants, diabetes increased the risk of hepatitis A infection by 40%.

Research conclusions

Hepatitis A is not a cause of diabetes. Instead, diabetes increases the risk of hepatitis A infection.

Research perspectives

Since hepatitis A mortality increases in patients with diabetes, hepatitis A vaccination is highly recommended in patients with diabetes.