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 characterized. 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 analyzed using random-effects proportional meta-analysis. Revised Cochrane risk of bias tool for randomized trials 2 and Risk of Bias in Nonrandomized Studies of Interventions I were used for assessing risk of bias.

RESULTS

Twenty-six studies with 1,963 participants were included. Proportion attaining complete resolution of MASH without worsening of fibrosis was 0.12 (95% confidence interval [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 affected by body mass index, type 2 diabetes mellitus, 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.