Meta-analysis of clinically available pharmacotherapy of biopsy confirmed metabolic dysfunction associated steatohepatitis (MASH).

AIMS: Pharmacotherapy for metabolic associated steatotic liver disease (MASLD) is reserved for steatohepatitis (MASH) with moderate Fibrosis Grades 2-3. Randomised controlled trials (RCT) of clinically available medications with biopsy data were evaluated for treatment benefits in steatohepatitis. MATERIALS AND METHODS: PUBMED, Cochrane, and Scopus databases were searched for 'MASH/NASH/NAFLD/randomised-controlled trials/liver biopsy' (N = 848 publications) which provided 14 publications with biopsy data. Outcomes were changes in biopsy MASLD Activity Scores (MAS), Fibrosis Grades, resolution of MASH with no worsening of liver fibrosis (RSw/oF) or reduction ≥1 fibrosis stage with no worsening of steatohepatitis (RFw/oS). Meta-analyses and meta-regression analyses were performed. RESULTS: There were 3173 subjects (age 53.1 ± 5.8 SD years). Steatohepatitis scores (MAS) improved with treatment versus placebo by mean difference (md) = -1.27 ± 0.16 SD Units, p < 0.001. MAS sub scores improved for steatosis, lobar inflammation, and ballooning for dapagliflozin, semaglutide, and pioglitazone (all p < 0.002). Fibrosis Grades improved compared to placebo (md = -0.352 ± 0.03 Units, p < 0.001). Relative rates (rr) of RSw/oF and RFw/oS were found with resmetirom, semaglutide, tirzepatide, and dapagliflozin (all p < 0.015). Changes in RSw/oF and RFw/oS inversely correlated with the baseline levels of Fibrosis Grades (p = 0.025, and p = 0.076 respectively), with greater improvements of both at lower Fibrosis Grades. CONCLUSIONS: Clinically available medications are beneficial in reversing MASH. Improvements in RSw/oF and RFw/oS were greater at earlier stages of fibrosis. Future analyses of drug effects should include assessments adjusted for baseline study characteristics of Fibrosis Grades and may evaluate whether preventive therapy will have long term benefits if started at earlier stages of MASLD.