Longitudinal risk of cirrhosis by steatotic liver disease subtype among 1.5 million individuals in the US.

BACKGOUND & AIMS: Steatotic liver disease (SLD), which includes metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic- and alcohol-associated liver disease (MetALD), and alcohol-associated liver disease (ALD), is the leading cause of chronic liver disease in the US. However, the risk of disease progression varies by subtype. We aimed to evaluate long-term risks of cirrhosis and mortality across SLD subtypes in a longudinal cohort of US veterans.

METHODS

Adults with MASLD, MetALD, and ALD were identified using the national Veterans Affairs health system database (2010-2023). Incidence of cirrhosis and all-cause mortality was stratified by SLD subtype and analyzed using competing risks and Cox proportional hazards models, adjusted for demographic and clinical covariates.

RESULTS

Overall, 682,274 veterans had MASLD, 517,464 had MetALD, and 305,692 had ALD, with a median follow up of 7.2 years. The highest cirrhosis incidence was observed in ALD (0.66 per 100 person-years vs. 0.43 and 0.39 per 100 person-years in MASLD and MetALD, respectively, p <0.001). Mortality incidence was likewise highest in ALD (0.32 per 100 person-years), compared with MASLD (0.24 per 100 person-years) and MetALD (0.19 per 100 person-years) (p <0.001). Across subtypes, relative to non-Hispanic Whites, Hispanics had higher risk and African Americans lower risk of cirrhosis. The additive effect of concurrent obesity and diabetes was associated with 36% and 22% increased risk of cirrhosis in MASLD and MetALD, respectively, compared to patients without obesity or diabetes.

CONCLUSIONS

Among US veterans with SLD, the long-term risk of cirrhosis was highest in ALD, followed by MASLD and MetALD. Concurrent metabolic dysfunction and alcohol use exert a synergistic effect on cirrhosis risk, underscoring the need to aggressively address metabolic comorbidities and implement early screening and treatment for harmful alcohol use.

IMPACT AND IMPLICATIONS: Given the growing burden of steatotic liver disease (SLD) in the US, it is crucial to understand how different causes - namely alcohol use and metabolic dysfunction - contribute to the risk of developing cirrhosis. This large, national study demonstrates that patients with alcohol-related liver disease face the highest risk, with notable variation by race and ethnicity. These findings are especially important for clinicians and healthcare systems caring for diverse populations, as they highlight groups at elevated risk who may benefit from targeted prevention and early intervention strategies. Practically, these results support the need for integrated care approaches that address both harmful alcohol use and metabolic conditions like obesity and diabetes to reduce progression to advanced liver disease.