Lean or diabetic subtypes predict increased all-cause and disease-specific mortality in metabolic-associated fatty liver disease

Background: Metabolic-associated fatty liver disease (MAFLD) encompasses diverse disease groups with potentially heterogeneous clinical outcomes. We investigated the risk of all-cause and disease-specific mortality in MAFLD subgroups. Methods: Using the Korean National Health Insurance Service database, participants were divided into four subgroups: no MAFLD, MAFLD-diabetes, MAFLD-overweight/obese, and MAFLD-lean. Hazard ratios (HRs) and 95% confidence interval (CI) values for all-cause and disease-specific mortality according to MAFLD subgroups were analyzed using Cox proportional hazards models. Results: Among 9,935,314 participants, those with MAFLD-diabetes showed the highest risk of all-cause and disease-specific mortality. The HRs (95% CI) for all-cause mortality were 1.61 (1.59-1.63), 1.36 (1.34-1.38), and 1.19 (1.18-1.20) in the MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obese groups, respectively. The magnitude of cardiovascular disease and cancer-related risk showed the same pattern. The risk of liver-related mortality in the MAFLD-lean group (HR: 2.84, 95% CI: 2.72-2.97) was comparable with that in the MAFLD-diabetes group (HR: 2.85, 95% CI: 2.75-2.95). When stratified by body mass index, liver-related mortality was the highest in MAFLD-lean individuals in the underweight group (HR, 5.03, 95% CI: 4.23-5.97). Conclusions: The MAFLD-lean and MAFLD-diabetes groups had a higher risk of all-cause and disease-specific mortality than did the MAFLD-overweight/obese group. Classifying MAFLD subgroups based on metabolic phenotypes might help risk stratification of patients with MAFLD.