SAT-662 GLP-1 And Advanced NASH: Impact On Liver Fibrosis Regression

Abstract Disclosure: A.C. Bocato: None. L.H. Baasch: None. V.L. Pin: None. A.V. Joia: None. L.C. Batista: None. B.S. Ribeiro: None. L.A. Morgado: None. L.L. Morikawa: None. J.P. Rodrigues: None. P.C. Souza: None. V.H. Bernardes: None. S.O. Bezerra: None. Introduction: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), frequently associated with obesity and type 2 diabetes. Its pathophysiology is mainly linked to insulin resistance. NAFLD affects up to 75% of individuals with type 2 diabetes and raises the risk of advanced fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained interest for their beneficial effects on hepatic steatosis, inflammation, and fibrosis. This study aims to assess their impact in patients with advanced NASH (F3/F4), focusing on histological regression, ALT/AST levels, and noninvasive fibrosis scores. Methods: A systematic review was conducted under PRISMA guidelines. The searches were conducted in PubMed, Cochrane Library and VHL using both subject and advanced search options with keywords relating to GLP-1 agonists and advanced NASH. Only clinical and observational studies published within the last decade that included patients with F3/F4 fibrosis staged by liver biopsy or elastography were considered. After screening, six studies were included in the final sample. Results: Semaglutide showed greater efficacy in resolving NASH compared to other agents, although its impact on fibrosis regression was limited. Tirzepatide outperformed dulaglutide in reducing inflammatory and fibrotic markers. Liraglutide had similar effects, notably contributing to fibrosis stage stabilization. The combination of exenatide and dapagliflozin proved more effective in improving FLI, NLFS, FIB-4, liver transaminases, and insulin resistance. Positive outcomes were also observed with exenatide alone in patients with severe obesity. Overall, GLP-1 receptor agonists demonstrated low discontinuation rates and a favorable safety profile, highlighting their potential in managing advanced NASH, particularly in individuals with type 2 diabetes and obesity. Conclusion: Liraglutide and semaglutide showed convincing effects on NASH resolution, regression of fibrosis, and liver bio-markers relating to inflammation in patients suffering from type 2 diabetes and advanced fibrosis while keeping a safe profile. These results highly encourage the use of these medications for advanced NASH. Presentation: Saturday, July 12, 2025