(A-123) A comparative efficacy of anti-fibrotic drugs on NASH: A systematic review and Network meta-analysis

Background: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with limited treatment options. Many antidiabetic drugs are used to treat NASH but targeted therapies remain limited.

Objectives: This study aims to assess the efficacy of pharmacological interventions in improving fibrosis and NASH resolution, including its components: inflammation, steatosis, ballooning, AST, and ALT.

Methods: This meta-analysis was registered in PROSPERO (CRD42023471965), included nine relevant studies identified through a search of PubMed and Google Scholar as of January 1, 2025. Studies evaluating the efficacy of cenicriviroc, simtuzumab, emricasan, belapectin, and selonsertib were included in the analysis. The primary outcome was improvement in fibrosis stage and NASH resolution, while the secondary outcomes included improvement in fibrosis components such as steatosis, ballooning, and inflammation, as well as the effect on AST and ALT levels. The forest plot, netgraph, and funnel plot were generated using the netmeta package in R.

Results: We ranked pharmacological interventions against the lowest-ranked treatment. Cenicriviroc (CVC) had the highest probability of achieving ≥1 stage fibrosis improvement (RR: 5.68, SUCRA: 0.99), while Simtuzumab (125 mg) was the most effective for NASH resolution (RR: 7.47, SUCRA: 0.86). For ballooning, placebo ranked highest (RR: 3.79, SUCRA: 0.97), followed by CVC (RR: 2.87, SUCRA: 0.67). Emricasan (50 mg and 5 mg) significantly reduced ALT levels (SMD: -0.66 and -0.53, SUCRA: 0.90 and 0.78). However, no significant differences were observed for AST, steatosis, or inflammation. All treatments did not show a significant advantage over placebo.

Conclusions: Our study ranks NASH therapies based on their effectiveness in improving fibrosis and NASH resolution. Combining antifibrotic drugs with those that resolve NASH may improve treatment outcomes, but further research is needed.