Clinical Features and Outcomes of Lean Metabolic Dysfunction-Associated Steatotic Liver Disease With Increased...

Metabolic dysfunction-associated steatotic liver disease with increased alcohol intake is a distinct clinical entity characterized by hepatic steatosis driven by both metabolic syndrome and alcohol use. This study aimed to characterize the clinical presentation and evaluate major liver outcomes and all-cause mortality in patients with lean vs nonlean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake.

We conducted a retrospective cohort study using data from the Veterans Analysis of Liver Disease (VALID) cohort. Lean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake was defined as metabolic dysfunction-associated steatotic liver disease with increased alcohol intake in individuals with a body mass index <25 kg/m² (<23 kg/m² in Asians). We used a multivariable Fine and Gray competing risk model to assess the association between lean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake and major liver outcomes and all-cause mortality.

A total of 98,076 veterans with metabolic dysfunction-associated steatotic liver disease with increased alcohol intake were included, of whom 12,613 met criteria for lean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake, between January 1, 2011, and December 31, 2022, with follow-up through May 31, 2023. Patients with lean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake had a higher Alcohol Use Disorders Identification Test-Concise score, and higher aspartate aminotransferase to alanine aminotransferase ratio (aspartate aminotransferase > alanine aminotransferase; 42.9 vs 37.9 IU/mL), whereas patients with nonlean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake had more cardiometabolic risk factors and aspartate aminotransferase < alanine aminotransferase (38.1 vs 49.3 IU/mL). Lean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake was independently associated with a 28% higher risk of major liver outcomes (adjusted hazard ratio, 1.28; 95% confidence interval, 1.18-1.38) and a 82% higher risk of all-cause mortality (adjusted hazard ratio, 1.82; 95% confidence interval, 1.74-1.91) compared with nonlean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake.

Patients with lean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake displayed clinical features more consistent with alcohol-associated liver disease, whereas patients with nonlean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake were clinically more similar to metabolic dysfunction-associated steatotic liver disease. Lean metabolic dysfunction-associated steatotic liver disease with increased alcohol intake is associated with significantly increased risks of liver-related complications and mortality, reinforcing the need for tailored management strategies targeting alcohol use disorder for this high-risk subgroup.