Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 14, 2024; 30(10): 1346-1357
Published online Mar 14, 2024. doi: 10.3748/wjg.v30.i10.1346
Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China
Jing-Feng Chen, Zhuo-Qing Wu, Hao-Shuang Liu, Su Yan, You-Xiang Wang, Miao Xing, Xiao-Qin Song, Su-Ying Ding
Jing-Feng Chen, Hao-Shuang Liu, Su Yan, Xiao-Qin Song, Su-Ying Ding, Health Management Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Zhuo-Qing Wu, Institute of Systems Engineering, Dalian University of Technology, Dalian 116024, Liaoning Province, China
You-Xiang Wang, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Miao Xing, School of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
Author contributions: Chen JF and Ding SY designed the study and acquired funding; Chen JF and Wu ZQ were responsible for developing the methodology; Yan S and Wang YX participated in the formal analysis and investigation; Chen JF wrote the original draft; Chen JF, Wu ZQ, Liu HS, Yan S, Wang YX, Xing M, Song XQ, and Ding SY participated in the review and editing.
Supported by National Natural Science Foundation of China, No. 72101236; China Postdoctoral Science Foundation, No. 2022M722900; Collaborative Innovation Project of Zhengzhou City, No. XTCX2023006; and Nursing Team Project of the First Affiliated Hospital of Zhengzhou University, No. HLKY2023005.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University (Approval No. 2020-KY-381).
Informed consent statement: Signed informed consent was obtained from all participants.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Su-Ying Ding, MD, Director, Doctor, Health Management Center, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu Middle Ring Road, Jinshui District, Zhengzhou 450052, Henan Province, China. fccdingsy@zzu.edu.cn
Received: November 7, 2023
Peer-review started: November 7, 2023
First decision: December 27, 2023
Revised: January 12, 2024
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: March 14, 2024
Processing time: 128 Days and 2.7 Hours
ARTICLE HIGHLIGHTS
Research background

Additional evidence is needed regarding the association between repeated high-normal alanine transaminase (ALT) measurements and metabolic dysfunction-associated fatty liver disease (MAFLD), and only a few cross-sectional studies have shown that ALT trajectory is associated with the risk of MAFLD. In light of the public health burden of MAFLD in China, we investigated the association between persistently elevated high-normal ALT levels and new-onset MAFLD using an ambispective cohort from a health examination population.

Research motivation

MAFLD has become a growing public health problem and affects up to one-third of the global population, with a heavy disease burden. MAFLD can occur in the presence of normal ALT levels, and a trajectory within the normal range can increase the risk of MAFLD. However, the link between repeated high-normal ALT measurements and new-onset MAFLD has not been well studied.

Research objectives

We investigated the optimal ALT cut-off points for diagnosing MAFLD and the association between repeated high-normal ALT measurements and the risk of new-onset MAFLD in a health examination population in China.

Research methods

This study used data from an ambispective cohort of individuals from a health examination population in China. Repeated high-normal ALT measurements were assessed by considering equally and unequally weighted cumulative effects of excess high-normal ALT (ehALT), and participants were categorized into quartile groups. We performed multivariable Cox proportional hazards regression analysis to evaluate the association between cumulative ehALT and the risk of new-onset MAFLD and calculated the hazard ratios (HRs) and 95% confidence intervals.

Research results

A total of 83.13% of participants with MAFLD had normal ALT levels. The HRs of new-onset MAFLD in the group of patients with 2 or 3 cumulative episodes of ehALT (Q3 and Q4 for the equally and unequally weighted cumulative effects of ehALT) were greater than those in the group with low-normal ALT levels from 2017 to 2019. Additionally, the dose-response relationship indicated that the equally and unequally weighted cumulative effects of ehALT had positive nonlinear relationships with the risk of new-onset MAFLD.

Research conclusions

A cohort study of the Chinese adult population revealed that persistently elevated high-normal ALT levels were associated with a dose-dependent increase in the risk of new-onset MAFLD in all participants. The identification and management of high-normal ALT levels for several years may play a crucial role in preventing MAFLD.

Research perspectives

Long-term prospective cohort or randomized controlled trials are needed to confirm the relationship between repeated high-normal ALT measurements and new-onset MAFLD. Future studies should focus on whether a healthy lifestyle can improve ALT levels and prevent MAFLD.