S2861 Representation of Lean Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease in Randomized Controlled Trials: A Systematic Review of Methodology

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, with 7%-20% of affected individuals presenting with a lean body habitus. Emerging evidence implicates metabolic and distinct polygenic factors in lean individuals that may influence treatment response. We conducted a systematic review to evaluate how pharmacologic trials use body mass index (BMI) eligibility and report BMI-related outcomes in lean individuals with MASLD. Methods: We conducted a systematic review of methods used in randomized controlled trials (RCTs) in accordance with PRISMA guidelines. PubMed, Embase, and Cochrane CENTRAL were searched for RCTs published between January 1, 2019 and April 30, 2025 in the English Language. Eligible studies included RCTs of pharmacologic therapies for MASLD or metabolic dysfunction-associated steatohepatitis based on biopsy- or imaging-confirmed diagnoses in adults. Retrospective studies, studies using herbal therapies or obeticholic acid, and studies lacking liver-related outcomes were excluded. We assessed BMI-based eligibility criteria and BMI-related outcome reporting, with lean individuals defined as having a BMI <25 kg/m² (or <23 kg/m² for Asian populations). Results: From 780 records identified, 738 unique abstracts were screened after de-duplication. Of these, 141 full-text articles were reviewed, and 71 RCTs were included in the final analysis. Our results showed that BMI-based inclusion or exclusion criteria were applied in 34 trials (48%). Of the 34 trials with BMI restrictions, 20 trials (59%) explicitly excluded lean individuals, and 18 trials (53%) excluded participants with class III or IV obesity. The pooled weighted mean BMI across all studies (N = 10,741 participants) was 32.9 kg/m², with a median study-level mean of 31.3 kg/m² (IQR: 29.0-34.9 kg/m²). Only 4 trials explicitly included a lean subgroup; of these, just one trial reported BMI-stratified outcomes, demonstrating hepatic fat reduction with empagliflozin pharmacotherapy in non-diabetic lean patients. A subset of studies adjusted for BMI in statistical models or conducted subgroup analyses based on weight change. Conclusion: Despite emerging interest, lean patients with MASLD remain markedly underrepresented in RCTs. Even when included, outcome reporting is rarely stratified by BMI, and sample sizes are often underpowered, limiting the generalizability of pharmacologic treatment data in this population.