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

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

World J Hepatol. 2023 Jun 27;15(6):813-825. doi: 10.4254/wjh.v15.i6.813.

Authors

Jia-Rui Zheng¹, Zi-Long Wang¹, Su-Zhen Jiang¹, Hong-Song Chen¹, Bo Feng²

Affiliations

¹ Peking University Hepatology Institute, Peking University People's Hospital, Beijing 100044, China.
² Peking University Hepatology Institute, Peking University People's Hospital, Beijing 100044, China. fengbo@pkuph.edu.cn.

Abstract

Background: Serum alanine aminotransferase (ALT) levels are often considered a marker to evaluate liver disease and its severity.

Aim: To investigate the association between ALT levels and all-cause and cause-specific mortality in patients with nonalcoholic fatty liver disease (NAFLD).

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.

Results: Multivariate logistic regression analysis demonstrated that the odds ratio of NAFLD correlated positively with increased serum ALT levels. 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.

Conclusion: 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.

Keywords: Alanine aminotransferase; Mortality; NHANES-III; Non-alcoholic fatty liver disease.