Hepatic Outcomes in Lean Versus Nonlean Metabolic Dysfunction-Associated Steatotic Liver Disease: Propensity-Matched...

Area of Science:

• Hepatology
• Internal Medicine
• Public Health

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent.
• The long-term hepatic risks associated with lean MASLD remain understudied compared to obese MASLD.
• Understanding differential risks is crucial for effective patient management and screening.

Purpose of the Study:

• To evaluate the differential risk of progressive hepatic outcomes in lean MASLD versus nonlean MASLD.
• To identify predictors of adverse outcomes specifically within the lean MASLD phenotype.
• To inform screening and surveillance strategies for MASLD across different body mass index categories.

Main Methods:

• A large, multicenter retrospective cohort study utilizing the TriNetX Global Health Research Network.
• Inclusion of adults with noncirrhotic MASLD between 2010 and 2024.
• Lean MASLD defined as BMI < 25 kg/m²; comparison with nonlean (BMI ≥ 25 kg/m²) and obese (BMI ≥ 30 kg/m²) MASLD groups.
• Outcomes assessed included fibrosis, cirrhosis, portal hypertension, HCC, liver transplantation, and mortality over 3, 5, and 10 years.
• Propensity score matching and multivariable Cox regression analyses were employed.

Main Results:

• Lean MASLD was associated with significantly higher odds of fibrosis, cirrhosis, portal hypertensive complications, HCC, liver transplantation, and mortality compared to nonlean, overweight, and obese MASLD.
• These associations remained consistent across all assessed time horizons (p < 0.001).
• Within the lean MASLD cohort, older age, diabetes, hypoalbuminemia, thrombocytopenia, and elevated AST independently predicted adverse hepatic outcomes.

Conclusions:

• Lean MASLD is linked to significant long-term hepatic morbidity and mortality.
• Current MASLD screening and risk stratification paradigms are primarily obesity-centered.
• There is a critical need to ensure lean individuals with MASLD are not under-screened or under-surveilled due to their higher risk profile.