Uncommon Combination of Low Alanine Aminotransferase and High Fatty Liver Index Associated With High Charlson Comorbidity Index: Insights From the K7Ps-Study-7

Abstract

Background: Elevated serum alanine aminotransferase (ALT) often reflects fatty liver, whereas low ALT has been reported as a predictor of frailty and increased mortality. However, the association between ALT and the Charlson Comorbidity Index (CCI), a measure of comorbidity and long-term mortality, is unknown. Therefore, this study aimed to investigate the association, particularly focusing on the fatty liver index (FLI) and physical characteristics, in a community-based cross-sectional study.

Methods: We examined liver enzymes, CCI, and cardiometabolic factors in 6,418,215 individuals without hepatic cirrhosis. Participants were classified into normal FLI (< 30, n = 4,418,623, NFG) and high FLI group (≥ 30, n = 1,999,592, HFG). A generalized linear model (GLM) was used to assess the association between ALT and CCI.

Results: Overall, all variables including CCI, but except for high-density lipoprotein cholesterol and prevalence of women, were higher in HFG than NFG. Age, CCI, and prevalence of cardiovascular disease and stroke increased with rising ALT levels in NFG, whereas they decreased in HFG (all P < 0.0001, linear regression and Cochran–Armitage trend test). Individuals with lower ALT were older, more often women, and those with lower physical capacity in HFG. Results of GLM demonstrated a U-shaped association between ALT and CCI, with the lowest point at ALT 20–29 U/L, after adjusting for covariates in NFG. By contrast, in HFG, lowest ALT of < 10 U/L (n = 17,261, 0.9%) was most associated with CCI than any other categories of ALT, with the lowest point at ALT of 30–49 U/L. Such trends were not observed in aspartate aminotransferase and γ-glutamyl transferase.

Conclusions: The uncommon combination of low ALT and fatty liver may be associated with high CCI, and older and more often women with the aspects of frailty, which was disclosed by the consideration of fatty liver, suggesting a phenomenon related to obesity paradox.