The relationships between MASLD, extrahepatic multimorbidity and all-cause mortality in UK Biobank cohort.

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.