Abstract
BackgroundWe examined whether total and regional fat-to-muscle ratio (FMR) predicts incident metabolic dysfunction-associated steatotic liver disease (MASLD) and other chronic liver outcomes.MethodsAmong 356,833 UK Biobank participants (men: 168,784 [47.3%]; women: 188,049 [52.7%]; mean age 56.3 years), body composition was assessed by segmental bioelectrical impedance analysis (BIA), from which whole-body and regional (arm, leg, trunk) FMRs were derived and categorized into sex-specific tertiles. Tertile cutpoints (lower and upper) were: men – whole-body (0.309, 0.396), arm (0.264, 0.333), leg (0.254, 0.325), trunk (0.348, 0.453); women – whole-body (0.526, 0.679), arm (0.500, 0.692), leg (0.640, 0.778), trunk (0.462, 0.621). Cox proportional hazards models were applied. MRI subsets included liver proton density fat fraction (PDFF) (n = 32,191) and hepatic fibro-inflammation (iron-corrected T1 [cT1]) (n = 27,028).ResultsOver a median follow-up of 14.0 years, there were 4,404 MASLD, 1,392 cirrhosis, 947 liver-related mortality, and 147 HCC events. Comparing the highest (T3) versus the lowest (T1) tertile of FMR, MASLD risk increased in both sexes across whole-body and regional FMRs (HR 2.29-2.76), with the strongest associations for leg FMR in women (HR 2.95). For cirrhosis and liver-related mortality, T3 associations were mainly seen in men and were strongest for whole-body and trunk/arm FMR (HR 1.63-2.11), while women showed weak/null associations (HR 1.29-1.54). For HCC, T3 FMR was strongly associated in men (HR 3.03-4.71), while no clear associations were evident in women.ConclusionHigher total and regional FMR predicts MASLD and advanced liver outcomes with clear sex- and region-specific patterns.