Associations of Coexisting Metabolic Dysfunction‐Associated Steatotic Liver Disease and Sarcopenia‐Related Abnormalities With Adverse Clinical Outcomes Across Obesity States

ABSTRACT

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is associated with adverse liver and non‐liver outcomes, but the impact of coexisting sarcopenia‐related abnormalities (e.g., low muscle strength [MS], muscle mass, and physical performance) remains unclear. In a prospective UK Biobank cohort ( n = 438,748), we evaluated their joint associations with incidence and risks of all‐cause mortality, cirrhosis, hepatocellular carcinoma (HCC), cardiovascular disease (CVD), chronic kidney disease (CKD), non‐liver cancers, and obesity‐related cancers across MASLD and sarcopenia‐related abnormality status. Over a median follow‐up of 13.8 years, 401 HCC, 1714 cirrhosis, 39,534 CVD, 19,637 CKD, 38,240 non‐liver cancers, 12,536 obesity‐related cancers, and 34,801 deaths occurred. A stepwise increase in both incidence and adjusted risk of liver and non‐liver outcomes was observed across MASLD and sarcopenia strata. Within the coexistence group, the obesity (vs. non‐obesity) subgroup generally had higher risks. For example, for cirrhosis, adjusted hazard ratios increased from 3.93 to 7.36 then 8.48 with MASLD alone, coexisting MASLD with low MS overall and coexisting MASLD, low MS and obesity, respectively. Similar findings were observed in external validation analyses using the 2011–2018 US National Health and Nutrition Examination Survey cohort. Together, these observations inform risk stratification strategy and management of MASLD to include sarcopenia assessment.