Metabolic dysfunction-associated fatty liver disease and risks of incident coronary artery disease and cerebrovascular disease: LIFE Study

Hepatol Res. 2025 Jun;55(6):807-817. doi: 10.1111/hepr.14185. Epub 2025 Mar 27.

Abstract

Aim: To estimate the risks of coronary artery and cerebrovascular diseases in metabolic dysfunction-associated fatty liver disease (MAFLD) using different fatty liver index (FLI) cut-off values in a Japanese population.

Methods: We analyzed insurance claims and health checkup data from public medical insurance enrollees aged ≥40 years in seven Japanese municipalities who had undergone a health checkup between April 2015 and March 2022. The MAFLD cases were identified as hepatic steatosis (defined as FLI ≥60 or ≥37) with overweight/obesity, diabetes, or lean/normal weight with metabolic dysregulation. Cox proportional hazards models estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for MAFLD (reference: non-MAFLD) regarding incident coronary artery and cerebrovascular diseases. Covariates included age, sex, smoking habit, low-density lipoprotein cholesterol level, and statin use.

Results: The study was undertaken using 163 834 individuals. The HRs of MAFLD for coronary artery disease were 1.44 (95% CI, 1.24-1.67) for FLI ≥ 60 and 1.49 (95% CI, 1.32-1.68) for FLI ≥ 37. The HRs of MAFLD for cerebrovascular disease were 1.58 (95% CI, 1.22-2.05) for FLI ≥ 60 and 1.41 (95% CI, 1.15-1.74) for FLI ≥ 37. In women, neither FLI cut-off was associated with coronary artery disease, and only FLI ≥ 60 was associated with cerebrovascular disease.

Conclusions: The MAFLD cases identified using the two FLI cut-off values were at higher risk for coronary artery and cerebrovascular diseases. Asian-specific FLI cut-offs may better identify hepatic steatosis in Japan than Western-specific cut-offs, but there is a need to consider sex differences when determining at-risk subgroups for targeted health interventions.

Keywords: atherosclerotic cardiovascular disease; dyslipidemia; fatty liver index; hepatic steatosis; hypertension; impaired glucose tolerance.