Hepatic Outcomes in Lean Versus Nonlean Metabolic Dysfunction–Associated Steatotic Liver Disease: Propensity‐Matched Cohort Study

ABSTRACT Background and Aims Lean metabolic dysfunction–associated steatotic liver disease (MASLD) is increasingly recognized; however, its long‐term hepatic risk relative to obese MASLD remains elusive. This study evaluated differential risk of progressive hepatic outcomes and identified predictors of adverse outcomes within the lean phenotype. Methods A large, multicenter retrospective cohort study was conducted using the TriNetX Global Health Research Network, including adults with noncirrhotic MASLD between 2010 and 2024. Lean MASLD was defined as the body mass index (BMI) < 25 kg/m 2 . Primary analyses compared lean versus nonlean MASLD (BMI ≥ 25 kg/m 2 ), with a prespecified secondary analysis comparing lean versus obese MASLD (BMI ≥ 30 kg/m 2 ), excluding overweight individuals. Outcomes included incident fibrosis, cirrhosis, portal hypertension and related complications, hepatocellular carcinoma (HCC), liver transplantation, and all‐cause mortality over 3‐year, 5‐year, and 10‐year follow‐up. Propensity score matching and multivariable Cox regression were applied. Results Among 1,130,297 patients with MASLD, 229,084 had lean MASLD. After matching, lean MASLD was associated with consistently higher odds of fibrosis, cirrhosis, portal hypertensive complications, HCC, liver transplantation, and mortality compared with nonlean, overweight, and obese MASLD across all time horizons (all p < 0.001). Within the lean MASLD cohort, those with older age, diabetes, hypoalbuminemia, thrombocytopenia, and elevated aspartate aminotransferase independently predicted adverse hepatic outcomes. Conclusions Lean MASLD is associated with substantial long‐term hepatic morbidity and mortality. Currently, obesity‐centered paradigms guide MASLD screening and risk stratification. Thus, efforts should be made to ensure that lean individuals with MASLD are not systematically under‐screened or under‐surveilled for progressive liver disease as they carry a higher risk of worsening.