Published online Jun 27, 2023. doi: 10.4254/wjh.v15.i6.813
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
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.
This study aimed to investigate the association between ALT levels and all-cause and cause-specific mortality in patients with NAFLD.
To give the clinicians a hint about the patients with NAFLD who have lower ALT levels.
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.
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.
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.
The underlying mechanism about the lower ALT levels and high mortality death is unclear and needs further research.