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

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.

This study aimed to estimate the impact of MASLD, with and without multimorbidity, on all-cause mortality.

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.

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.

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.