Cause-specific mortality in lean individuals with metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) can occur in both nonlean and lean individuals. This study aimed to compare the risk of cause-specific mortality between lean and nonlean MASLD patients and investigate the impact of advanced fibrosis on mortality. This population-based cohort study included 14,740 adults from the National Health and Nutrition Examination Survey (NHANES). The NAFLD Fibrosis Score (NFS) or Fibrosis-4 score (FIB-4) was employed to identify advanced fibrosis. Cox proportional hazard models were utilized to analyze all-cause mortality, whereas competing risk models were applied to analyze cause-specific mortality. During a median follow-up of 7.3 (4.1–10.7) years, lean MASLD patients presented increased risks for all-cause mortality (HR = 2.50, 95% CI = 1.70–3.66) and diabetes-specific mortality (sHR = 5.00, 95% CI = 1.40–17.8) compared with nonlean MASLD patients. No significant differences were observed in cardiovascular-specific or cancer-specific mortality risk between the two groups. Stratified analyses revealed a significant interaction effect between lean MASLD and advanced fibrosis on all-cause mortality risk. Among lean MASLD patients with advanced fibrosis, the incidence rates per 1,000 person-years were 110.6 (95% CI = 58.5-185.2) for all-cause mortality, 27.7 (5.7–78.7) for cardiovascular-specific mortality, 9.2 (0.2–50.3) for cancer-specific mortality and 9.2 (0.2–50.3) for diabetes-specific mortality. An FIB-4 score > 2.67 and NFS > 0.676 could indicate an increased risk of all-cause mortality in lean MASLD patients, with no significant difference in performance. Lean MASLD patients had greater risks of all-cause and diabetes-specific mortality than nonlean MASLD patients, and regular noninvasive fibrosis evaluation is recommended for lean MASLD patients.