The Relationships Between MASLD, Extrahepatic Multimorbidity, and All-Cause Mortality in the UK Biobank Cohort

Abstract

CONTEXT: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one third of the world's population, but its associations with extrahepatic multimorbidity and mortality remain unclear. OBJECTIVE: This study aimed to estimate the impact of MASLD, with and without multimorbidity, on all-cause mortality. METHODS: We analyzed data from the UK Biobank. MASLD was identified as a fatty liver index ≥60 and presence of cardiometabolic risk factors. Multimorbidity was defined as ≥2 of the long-term conditions (LTCs) in a prespecified list of 47 extrahepatic conditions. Hazard ratios (HRs) from adjusted Cox models quantified the association between MASLD, multimorbidity and all-cause mortality. RESULTS: Of the 438 840 participants, 131 020 (29.9%) had MASLD at baseline. The participants with MASLD at baseline had a higher prevalence of multimorbidity than those without (21.3% vs 14.4%). In addition to cardiometabolic risk factors, MASLD was strongly associated with several LTCs, particularly metabolic, cardiovascular, cancers, kidney, mental/behavioral, and respiratory diseases. During a median follow-up of 13 years, MASLD was associated with higher mortality (HR 1.16; 95% CI 1.13, 1.19), with stronger associations in females and in those with low LTC counts (≤3 LTCs). Each additional LTC at baseline was associated with 30% and 38% higher mortality in MASLD (HR 1.30; 1.29, 1.32) and non-MASLD (HR 1.38; 1.37, 1.40) populations, respectively. Among the 47 LTCs, 16 were associated with increased mortality in people with MASLD. CONCLUSION: Those with MASLD exhibited a higher prevalence of extrahepatic multimorbidity and a 16% higher rate of mortality than those without, underscoring the impact of liver steatosis on mortality and highlighting the need to target LTCs to improve outcomes and reduce health care burdens.

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