Subtype Differences in Major Adverse Liver Outcomes and Cardiovascular Events and Mortality in Steatotic Liver Disease: A UK Biobank Analysis

BACKGROUND: The natural history of steatotic liver disease (SLD)-including major adverse liver outcomes (MALO), major adverse cardiovascular events (MACE), and all-cause mortality-remains inadequately defined in population-based settings. AIMS: We sought to quantify their incidence and compare risks across SLD subtypes. METHODS: We evaluated 244,760 UK Biobank participants, assessing metabolic dysfunction-associated SLD (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), or alcohol-associated liver disease (ALD), and examined outcomes across these subtypes. RESULTS: Among the cohort, 47,949 (19.6%) had MASLD, 23,000 (9.4%) had MetALD, and 8085 (3.3%) had ALD. Of the 79,034 individuals with SLD (mean age 57.2; 72.4% female; 98.0% White), the incidence rates of MALO (per 1,000 person-years) were 1.91 for MASLD, 2.35 for MetALD, and 5.80 for ALD during a median follow-up of 13.5 years. Corresponding rates for MACE were 14.88, 15.48, and 19.36, and for all-cause mortality were 12.99, 13.59, and 20.93. After adjustment, ALD (hazard ratio [HR], 2.95; 95% CI, 2.64-3.29) and MetALD (HR, 1.23; 95% CI, 1.11-1.36) were associated with higher MALO risk than MASLD. ALD also showed higher risks of MACE and mortality than MetALD (MACE: HR, 1.17; 95% CI, 1.10-1.24; mortality: HR, 1.49; 95% CI, 1.41-1.58) or MASLD (MACE: HR, 1.17; 95% CI, 1.11-1.24; mortality: HR, 1.52; 95% CI, 1.44-1.60), whereas MetALD and MASLD showed no differences. CONCLUSIONS: In the United Kingdom, ALD exhibited the highest liver, cardiovascular, and mortality risks, while MASLD and MetALD had similar cardiovascular and survival profiles but differed in liver-related risk.