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
Abstract
BACKGROUND

Within the normal range, elevated alanine aminotransferase (ALT) levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD).

AIM

To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD prospectively.

METHODS

A cohort of 3553 participants followed for four consecutive health examinations over 4 years was selected. The incidence rate, cumulative times, and equally and unequally weighted cumulative effects of excess high-normal ALT levels (ehALT) were measured. Cox proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset MAFLD.

RESULTS

A total of 83.13% of participants with MAFLD had normal ALT levels. The incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT group. Compared with those in the low-normal ALT group, the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651 [95% confidence interval (CI): 1.199-2.273] and 1.535 (95%CI: 1.119-2.106) in the third quartile and 1.616 (95%CI: 1.162-2.246) and 1.580 (95%CI: 1.155-2.162) in the fourth quartile, respectively.

CONCLUSION

Most participants with MAFLD had normal ALT levels. Long-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

Keywords: Metabolic dysfunction-associated fatty liver disease, High-normal alanine aminotransferase level, Cumulative effect, Cox proportional hazards regression, Cohort study

Core Tip: Limited evidence exists regarding the association between persistently elevated high-normal alanine transaminase (ALT) levels and the risk of new-onset metabolic dysfunction-associated fatty liver disease (MAFLD). This cohort study analysed 3553 participants followed for four consecutive health examinations between 2017 and 2020 and measured the cumulative effects of excess high-normal ALT (ehALT). Among the participants, the incidence rate of MAFLD showed a linear increasing trend for the cumulative ehALT group. The hazard ratios of new-onset MAFLD were significantly increased in the third and fourth quartiles of the equally and unequally weighted cumulative effects of ehALT. Among Chinese adults, long-term high-normal ALT levels were related to a cumulative increased risk of new-onset MAFLD.