Impact of steatotic liver disease subtypes, sarcopenia, and fibrosis on all-cause and cause-specific mortality: a 15.7-year cohort study

BackgroundSteatotic liver disease (SLD) was a newly proposed disease category derived from metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD and sarcopenia were independent risk factors for mortality. We aimed to evaluate the impacts of SLD subtypes, MAFLD, and sarcopenia on mortality.MethodsA total of 6543 subjects were identified from the National Health and Nutrition Examination Survey 1999-2006 with the latest Linked Mortality file. Hepatic steatosis, advanced fibrosis, and sarcopenia were determined by the laboratory- and anthropometry- based fatty liver index and fibrosis-4 index, and dual-energy X-ray absorptiometry-based appendicular skeletal muscle mass index, respectively. Associations of SLD subtypes, MAFLD, and sarcopenia with mortality were estimated using the weighted Cox proportional hazards model.ResultsDuring a mean follow-up time of 15.7 years, 1567 (16.7%) deaths occurred including 494 (4.9%) deaths from cardiovascular diseases and 372 (4.1%) from cancer. The all-cause mortality rates of MAFLD, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), other aetiology SLD, MASLD without sarcopenia, and MASLD with sarcopenia were 21.0%, 19.8%, 30.2%, 30.9%, 19.2%, and 75.5%, respectively. MAFLD increased the risk of all-cause mortality (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00-1.59). MASLD predicted all-cause mortality (HR 1.17, 95% CI 1.03-1.33) but this prediction became insignificant after adjustment for metabolic risks. In contrast, MetALD and other aetiology SLD were significantly associated with all-cause mortality (HR 1.83, 95% CI 1.21-2.76; HR 2.50, 95% CI 1.82-3.44, respectively), predominantly associated with cancer-specific mortality (HR 2.42, 95% CI 1.23-4.74; HR 2.49, 95% CI 1.05-5.90, respectively). MASLD with sarcopenia increased the risk of all-cause mortality by almost twice (HR 2.19, 95% CI 1.37-3.49) and further coexisting advanced fibrosis additively increased mortality (HR 3.41, 95% CI 1.92-6.05).ConclusionSLD definition identified a more homogeneous group with metabolically hepatic steatosis at higher risks of mortality. MASLD or MASLD-related advanced fibrosis and sarcopenia additively increased mortality.