Background & Aims: This study aimed to estimate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), with and without multimorbidity, on all-cause mortality. Methods: We analysed data from the UK Biobank. MASLD was identified as a fatty liver index (FLI) ≥ 60 and presence of cardiometabolic risk factors. Multimorbidity was defined as ≥2 of the long-term conditions (LTCs) in a pre-specified 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/behavioural, 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 healthcare burdens.

The authors have declared no competing interest.

This study did not receive any funding

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