Liver fibrosis index and mortality in metabolic dysfunction–associated steatotic liver disease: a Korean cohort study

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major public health concern. However, its relationship with the long-term mortality risk remains underexplored in the general population. We aimed to examine the association between liver fibrosis, assessed using the age-adjusted Fibrosis-4 (FIB-4) residual index, and all-cause and cardiovascular mortality in individuals with MASLD. This cohort study included 134,686 adults diagnosed with MASLD via ultrasonography and metabolic abnormalities during health screenings at two Korean centers between 2002 and 2022. The participants were followed up for mortality outcomes using the National Death Registry. The FIB-4 index was calculated from age, AST, ALT, and platelet count adjusted for age using residual modeling. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for all-cause and cardiovascular mortality, adjusting for sociodemographic, behavioral, and clinical covariates. Age-stratified analyses were also performed. During a mean follow-up of 11.2 years, 2,129 all-cause and 348 cardiovascular deaths occurred. A higher age-adjusted FIB-4 index was associated with increased risk of all-cause mortality (HR 1.489, 95% CI 1.353-1.639) and cardiovascular mortality (HR 1.478, 95% CI 1.175-1.860). These associations persisted after adjustment. In stratified analyses, all-cause mortality associations were significant in both age groups, whereas cardiovascular mortality was significant only in those aged > 39 years. The age-adjusted FIB-4 index was independently associated with increased risk of all-cause and cardiovascular mortality in patients with MASLD. Assessing liver fibrosis using FIB-4 may provide prognostic information beyond traditional cardiometabolic risk factors in this population.