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

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BACKGROUND: Steatotic 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. METHODS: A 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. RESULTS: During 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). CONCLUSION: SLD 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.

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