7622 The Effects of Fibroblast Growth Factor-21 Analogues in Patients with Metabolic Dysfunction Associated Steatohepatitis (MASH): A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Cardoso J C , Sudo R Y Ura , Souza M C , Pessôa F D , Moraes F A , Oliveira N M , Kelly F A , Lopes L M , Lima P G , Barros M S , Bandeira F F 
Published: October 2024

Disclosure: J.C. Cardoso: None. R.Y. Ura Sudo: None. M.C. Souza: None. F.D. Pessôa: None. F.A. Moraes: None. N.M. Oliveira: None. F.A. Kelly: None. L.M. Lopes: None. P.G. Lima: None. M.S. Barros: None. F.F. Bandeira: None.

Fibroblast growth factor 21 (FGF-21), has been proposed to improve liver histologic features, hepatic steatosis and markers of inflammation and fibrosis, thus emerging as a treatment avenue to metabolic dysfunction associated steatohepatitis (MASH). However, the potential treatment effects of FGF-21 analogues remain unclear. Therefore we aimed to perform a meta analysis exploring the effects on the liver of FGF-21 analogues when compared to placebo. We systematically searched different databases for randomized controlled trials (RCT): Pubmed, Web of Science, Cochrane - from inception to January 2024. Statistical analysis was performed in R software 4.3.1. A random-effects model was employed to compute mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) for continuous and binary endpoints, respectively. A p-value of &lt;0.05 was considered statistically significant. Heterogeneity was examined with the Cochran Q test, prediction interval and I² statistics. The results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guideline. The protocol was registered in PROSPERO (CRD42023493083). A total of 12 RCTs with 1235 patients were included, of whom 852 (69%) were randomized to FGF-21 analogues therapy. The mean age was 54 years and the mean body mass index (Kg/m²) was 39.1. Over a mean follow-up time of 31.667 weeks, the analysis showed us that while the ≥ 50% reduction in hepatic fat fraction (HFF) (RR 6.53; 95% CI 3.13 to 13.63; p &lt; 0.001; I² = 0%) and the fibrosis improvement in ≥1 stage without worsening of MASH (RR 1.77; 95% CI 1.12 to 2.79; P=0.0145; I² =29%) were significantly higher in patients treated with FGF-21 analogues compared with placebo, the higher MASH resolution without worsening of fibrosis (RR 2.48; 95% CI 0.87 to 7.08; P=0.090;I²=60%) in FGF-21 group wasn’t statistically significant. The FGF-21 group also presented significantly mean decreases in ELF score (MD -0.45; 95% CI -0.64 to -0.25; p &lt; 0.001; I² =34%), liver stiffness (MD -2.10 KPa; 95% CI -3.53 to -0.68; p = 0.004; I²=94%), GGT (MD -16.33 U/L; 95% CI -29.92 to -2.75; p=0.018; I²=81%), ALP (MD -7.95 U/L; 95% CI -11.53 to -4.37; p&lt;0.001; I²=0%), HFF (MD -40.26%; 95% CI -63.01 to -17.51; p &lt; 0.001; I²=97%), ALT (MD -19.31%; 95% CI -28.84 to -9.77; p&lt;0.001; I²=63%), AST (MD -19.32%; 95% CI -28.53 to -10.11; p&lt;0.001; I² =59%), Pro-C3 (MD -13.65%; 95% CI -21.93 to -5.38; p=0.001; I²=81%). In conclusion, the use of FGF-21 analogues significantly improves liver histologic features, inflammation and fibrosis, however there were nonsignificant improvement in the composite outcome of MASH resolution without worsening of fibrosis.

Presentation: 6/3/2024