Zheng JR, Wang ZL, Jiang SZ, Chen HS, Feng B. Lower alanine aminotransferase levels are associated with increased all-cause and cardiovascular mortality in nonalcoholic fatty liver patients. World J Hepatol 2023; 15(6): 813-825 [PMID: 37397938 DOI: 10.4254/wjh.v15.i6.813]
Corresponding Author of This Article
Bo Feng, MD, PhD, Chief Doctor, Professor, Research Fellow, Peking University Hepatology Institute, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China. fengbo@pkuph.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
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: http://creativecommons.org/licenses/by-nc/4.0/
World J Hepatol. Jun 27, 2023; 15(6): 813-825 Published online Jun 27, 2023. doi: 10.4254/wjh.v15.i6.813
Lower alanine aminotransferase levels are associated with increased all-cause and cardiovascular mortality in nonalcoholic fatty liver patients
Jia-Rui Zheng, Zi-Long Wang, Su-Zhen Jiang, Hong-Song Chen, Bo Feng
Jia-Rui Zheng, Zi-Long Wang, Su-Zhen Jiang, Hong-Song Chen, Bo Feng, Peking University Hepatology Institute, Peking University People's Hospital, Beijing 100044, China
Author contributions: Feng B designed the study; Zheng JR and Wang ZL contributed to the acquisition, analysis and interpretation of data and drafted the manuscript; Jiang SZ contributed to the critical revision of the manuscript for important intellectual content and Chen HS contributed to the study supervision; all authors have made a significant contribution to this study and have approved the final manuscript.
Institutional review board statement: The NHANES protocol was approved by the Ethics Review Committee of the National Center for Health Statistics, which obtained informed consent from all subjects.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: The authors have declared no conflict of interest.
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: Bo Feng, MD, PhD, Chief Doctor, Professor, Research Fellow, Peking University Hepatology Institute, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China. fengbo@pkuph.edu.cn
Received: October 19, 2022 Peer-review started: October 19, 2022 First decision: March 15, 2023 Revised: March 22, 2023 Accepted: May 16, 2023 Article in press: May 16, 2023 Published online: June 27, 2023 Processing time: 140 Days and 2.1 Hours
ARTICLE HIGHLIGHTS
Research background
Serum alanine aminotransferase (ALT) levels are greatly important in the liver disease but the role ALT levels play in the nonalcoholic fatty liver disease (NAFLD) is not clear.
Research motivation
This study aimed to investigate the association between ALT levels and all-cause and cause-specific mortality in patients with NAFLD.
Research objectives
To give the clinicians a hint about the patients with NAFLD who have lower ALT levels.
Research methods
The Third National Health and Nutrition Examination Survey (NHANES-III) from 1988 to 1994 and NHANES-III-related mortality data from 2019 onward were used to obtain the necessary data for the study. NAFLD was defined as hepatic steatosis, as diagnosed by ultrasound, with no other liver diseases. ALT levels were categorized into four groups according to the different recommended upper limits of normal (ULN) in men and women: < 0.5 ULN, 0.5-1 ULN, 1-2 ULN, and ≥ 2 ULN. The hazard ratios for all-cause mortality and cause-specific mortality were analyzed using the Cox proportional hazard model.
Research results
In patients with NAFLD, all-cause mortality and cardiovascular mortality were the highest when ALT was < 0.5 ULN, yet cancer-related mortality was the highest when ALT was ≥ 2 ULN. The same results could be found in both men and women. Univariate analysis showed that severe NAFLD with normal ALT levels had the highest all-cause and cause-specific mortality, but the difference was not statistically significant after adjustment for age and multivariate factors, both the underlying mechanism is unclear and needs further research.
Research conclusions
The risk of NAFLD was positively correlated with ALT level, but all-cause and cardiovascular mortality were the highest when ALT was < 0.5 ULN. Regardless of the severity of NAFLD, normal or lower ALT levels were associated with higher mortality than elevated ALT levels. Clinicians should be aware that high ALT levels indicate liver injury, but low ALT levels are associated with a higher risk of death.
Research perspectives
The underlying mechanism about the lower ALT levels and high mortality death is unclear and needs further research.
