Adverse Liver Outcomes, Cardiovascular Events, and Mortality in Steatotic Liver Disease

Importance: Steatotic liver disease is a major cause of advanced liver disease and is associated with increased risks of long-term adverse outcomes. However, estimates in steatotic liver disease subtypes according to the revised nomenclature are limited in population-based cohorts. Objective: To compare the risks of adverse liver outcomes, major adverse cardiovascular events (MACE), and all-cause mortality across steatotic liver disease subtypes. Design, Setting, and Participants: A retrospective cohort study of adults with imaging-confirmed hepatic steatosis receiving outpatient care within the national Veterans Health Administration (2010-2021) was carried out. Data were analyzed from April 2024 to March 2025. Exposures: Steatotic liver disease subtypes, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD), or their intersection (MetALD). Main Outcomes and Measures: The primary outcomes were the incidence of adverse liver outcomes (cirrhosis, decompensation, hepatocellular carcinoma, liver transplant, liver-related death), MACE (myocardial infarction, stroke, heart failure, cardiovascular death), and all-cause mortality. Results: Of 341 601 adults (mean [SD] age, 59.5 (13.2) years; 227 954 non-Hispanic White [66.7%]; 27 606 female [8.1%]), 264 192 had MASLD (77.3%), 61 070 had MetALD (17.9%), and 16 339 had ALD (4.8%). Over a median (IQR) follow-up of 5.5 (3.0-8.4) years, compared with MASLD, MetALD had a higher incidence of adverse liver outcomes (1.12 vs 0.61 per 100 person-years; hazard ratio [HR], 1.56; 95% CI, 1.50-1.62) and all-cause mortality (2.74 vs 2.60 per 100 person-years; HR, 1.08; 95% CI, 1.05-1.10), but similar incidence of MACE. ALD had a higher incidence of adverse liver outcomes (1.78 vs 0.61 per 100 person-years; HR, 2.33; 95% CI, 2.20-2.47) and all-cause mortality (3.42 vs 2.60 per 100 person-years; HR, 1.42; 95% CI, 1.36-1.48) than MASLD, but similar incidence of MACE. The incidence of adverse liver outcomes per 100 person-years increased 10-fold with a higher degree of fibrosis (Fibrosis-4 score <1.30 vs >2.67) across MASLD (0.28 vs 3.02), MetALD (0.39 vs 4.31), and ALD (0.61 vs 5.05). Severe alcohol use, alcohol use disorder, and diabetes were the factors most strongly associated with adverse liver outcomes. Conclusions and Relevance: This cohort study found that patients with MetALD and ALD had modestly higher risks of adverse liver outcomes and all-cause mortality than those with MASLD, with similar risks of MACE. Alcohol and fibrosis assessments may help identify patients at increased risk for long-term adverse outcomes.