Steatotic Liver Disease Subtypes Linked to Distinct Long-Term Risks in Veterans Cohort
A retrospective study of more than 340,000 patients within the Veterans Health Administration has shown that the risks of adverse liver outcomes and mortality vary significantly across steatotic liver disease subtypes, with alcohol-associated liver disease (ALD) and the overlapping MetALD phenotype carrying a greater burden than metabolic dysfunction-associated steatotic liver disease (MASLD).
The findings were published in JAMA Internal Medicine
Among 341,601 adults with imaging-confirmed hepatic steatosis, 77.3% had MASLD, 17.9% had MetALD (both metabolic dysfunction and alcohol-related features), and 4.8% had ALD alone. Over a median follow-up of 5.5 years, MetALD and ALD subtypes demonstrated higher incidence rates of liver complications and all-cause mortality compared to MASLD.
“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 (HR, 1.08; 95% CI, 1.05–1.10),” the authors reported. “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 (HR, 1.42; 95% CI, 1.36–1.48) than MASLD.”
The risk of major adverse cardiovascular events (MACE)—including myocardial infarction, stroke, heart failure, and cardiovascular death—was similar across all 3 groups, suggesting that cardiovascular risk may be less influenced by liver disease subtype and more by shared metabolic risk factors.
Fibrosis severity emerged as a strong predictor of liver-related complications across all subtypes. The incidence of adverse liver outcomes per 100 person-years increased more than 10-fold between the lowest and highest fibrosis strata. For MASLD, the incidence rose from 0.28 to 3.02; for MetALD, from 0.39 to 4.31; and for ALD, from 0.61 to 5.05, according to Fibrosis-4 score stratification.
“Severe alcohol use, alcohol use disorder, and diabetes were the factors most strongly associated with adverse liver outcomes,” the authors concluded, emphasizing the need to assess both alcohol exposure and fibrosis stage in routine clinical care.
These findings highlight the prognostic value of differentiating steatotic liver disease subtypes in clinical practice. Risk stratification using alcohol use history and fibrosis assessment can guide surveillance and intervention strategies to reduce the burden of liver-related and all-cause mortality across a growing population of patients with fatty liver disease.
Reference
Ochoa-Allemant P, Hubbard RA, Kaplan DE, Serper M. Adverse liver outcomes, cardiovascular events, and mortality in steatotic liver disease. JAMA Intern Med. Published online June 16, 2025. doi:10.1001/jamainternmed.2025.1809
