Safety and efficacy of pharmacological interventions for hepatic outcomes of metabolic dysfunction-associated steatotic liver disease: protocol for systematic review and network meta-analysis.

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of morbidity and mortality due to chronic liver disease. There is an extensive body of evidence focusing on pharmacotherapy for MASLD. Reviews on the topic have been largely limited to the efficacy of select agents, subgroups or outcomes. The current is a protocol for a comprehensive systematic review and network meta-analysis (NMA) evaluating the efficacy of examined pharmaceutical interventions in improving hepatic outcomes of MASLD.

METHODS AND ANALYSIS: MEDLINE, Scopus, Web of Science, the Cochrane Library database and multiple trial registries will be searched for clinical trials on MASLD pharmacotherapy. Histological, radiological and paraclinical outcomes will be considered along with safety and tolerability. Screening and data extraction will be conducted by pairs of independent reviewers. Risk of bias (RoB) will be assessed using the Cochrane RoB 2 tool. Pairwise random-effects meta-analyses will be conducted followed by random-effects frequentist NMAs-according to the length of intervention-for each outcome in clinically distinct MASLD subgroups. Other effect moderators will be examined in subgroup analyses and meta-regression. Certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation and Confidence in Network Meta-Analysis approaches.

ETHICS AND DISSEMINATION: Ethics approval was waived (Alborz University of Medical Sciences; approval ID: IR.ABZUMS.REC.1404.121) as no new data will be generated. Information from published records will be used in compliance with their Copyright agreements. Results will be submitted for peer review and publication in a scientific journal.

PROSPERO REGISTRATION NUMBER: CRD420251125615.