Efficacy and safety of the FGF19 analog aldafermin for the treatment of nonalcoholic steatohepatitis: a GRADE assessed systematic review and meta-analysis

Background: Nonalcoholic fatty liver disease (NAFLD) is increasingly concerning due to its rising prevalence. It encompasses conditions from simple steatosis to severe nonalcoholic steatohepatitis (NASH), posing risks such as fibrosis, cirrhosis, or hepatocellular carcinoma if untreated. This systematic review and meta-analysis aims to assess aldafermin, an FGF19 analog, for efficacy and safety in NASH patients.

Methods: Eligible studies were identified by searching PubMed, Cochrane Library, and Google Scholar, resulting in 1115 studies. Three RCTs were included. The risk of bias was assessed using the Cochrane Risk of Bias tool, and data synthesis utilized Review Manager software. The certainty of evidence was evaluated with the GRADE approach.

Results: In the 3 mg dose group, aldafermin significantly improved various parameters. The ELF score decreased notably (pooled MD: -0.46, 95% CI: -0.64 to -0.28; P<0.00001). Additionally, fibrosis improvement without NASH worsening showed a pooled MD of 8.15 (95% CI: -3.62 to 19.93; P<0.17), and fibrosis improvement with NASH resolution displayed a pooled MD of 10.16 (95% CI: 1.68-18.64; P=0.02). Furthermore, significant reductions were noted in absolute AST levels (pooled MD: -13.40, 95% CI: -18.66 to -8.14; P<0.00001) and absolute ALT levels (pooled MD: -19.92, 95% CI: -27.08 to -12.75; P<0.00001), suggesting improved liver function.

Conclusion: The meta-analysis indicates that aldafermin, particularly, the 3 mg dose, shows significant efficacy in improving liver histology and biochemical markers in NASH patients compared to placebo, along with a satisfactory safety profile.