S106 Efficacy and Safety of Peroxisome Proliferator-Activated Receptor Agonists in Primary Biliary Cholangitis: Systematic Review and Meta-Analysis

Introduction: Primary biliary cholangitis (PBC), an autoimmune liver disease, has the potential to advance to liver cirrhosis and result in fatality. Ursodeoxycholic acid is the first-line treatment, while obeticholic acid serves as a second-line option due to moderate ursodeoxycholic acid non-responsiveness and cirrhosis-related concerns. Additional therapies are necessary due to recent warnings regarding obeticholic acid usage in cirrhotic patients. This study aimed to evaluate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in PBC. Methods: We searched PubMed, Google Scholar, and the Cochrane Library until July 28, 2023. We included all randomized controlled trials that studied the efficacy and safety of PPAR agonists in treating PBC. The primary outcome of interest was alkaline phosphatase (ALP). In contrast, the secondary outcomes were gamma-glutamyl transferase (GGT), alanine transaminase, aspartate aminotransferase, total bilirubin (Tbili), triglyceride and pruritis. We used a random-effects model to calculate the risk ratio and standardized mean difference (SMD) with 95% CI. Results: A total of 8 randomized controlled trials (n = 515) were eligible for the analysis. Pooled data showed beneficial effects of PPAR agonists compared to placebo for ALP (SMD = -2.81, 95% CI = -4.10 to -1.51; P < 0.0001, I2 = 96%), GGT (SMD = -1.29, 95% CI = -2.09 to -0.48; P = 0.002, I2 = 92%), TBili (SMD = -0.77, 95% CI = -1.32 to -0.22; P = 0.006, I2 = 86%), and Tg (SMD = -0.99, 95% CI = -1.63 to -0.35; P = 0.003, I2 = 83%). There was no significant difference between PPAR agonists and placebo for alanine transaminase (SMD = -0.93, 95% CI = -1.94 to 0.08; P = 0.07, I2 = 95%), aspartate aminotransferase (SMD = -0.01, 95% CI = -0.67 to 0.66; P = 0.99, I2 = 91%), and pruritus (risk ratio = 0.77, 95% CI = 0.29 to 2.06; P = 0.60, I2 = 34%). Conclusion: Our study found a superior efficacy of PPAR agonists compared to placebo for ALP, GGT, Tbili, and Tg, highlighting the potentially beneficial effect of PPAR agonists on liver health.