The Impact of Body Weight Change on Liver Histology in Metabolic Dysfunction-Associated Steatotic Liver Disease Across Various Histological Endpoints: A Systematic Review and Meta-Analysis

Introduction: Weight loss is the cornerstone of treatment for metabolic dysfunction-associated liver disease (MASLD); however, its impact on liver histology across patient subgroups remains incompletely characterised. This systematic review and meta-analysis aimed to quantify the effects of body weight change across multiple histological endpoints in patients with biopsy-proven MASLD. Methods: PubMed, EMBASE, MEDLINE (Ovid) and Google Scholar were searched from inception for trials reporting percentage change in body weight in MASLD or metabolic dysfunction-associated steatohepatitis (MASH) patients with paired liver biopsies. Proportions of patients achieving the primary outcomes: complete resolution of MASH without worsening of fibrosis, and ≥1-stage fibrosis improvement without worsening of MASH, were analysed using random-effects proportional meta-analysis. RoB-2 and ROBINS-I were used for assessing risk of bias. Results: Twenty-six studies with 1963 participants were included. Proportion attaining complete resolution of MASH without worsening of fibrosis was 0.12 (95% CI: 0.08-016, I 2 =76%) which significantly improved with observed weight loss >3% (0.25, 95% CI: 0.20-0.30, p<0.001). Mean age significantly contributed to heterogeneity (p=0.021, R 2 =43%). Proportion attaining ≥1-stage fibrosis improvement without worsening of MASH was 0.17 (95% CI: 0.13-0.22, I 2 =62%). No significant differences were found based on baseline body mass index, type 2 diabetes mellitus prevalence, or Hispanic/Latino ethnicity. Discussion: Even modest observed weight loss is associated with MASH resolution. MASH resolution and ≥1-stage fibrosis improvement are not impacted by BMI, T2DM or Hispanic/Latino ethnicity, reinforcing the importance of lifestyle interventions across populations. The proportions observed serve as benchmark estimates of histological response for future clinical trial design.