S2711 Efficacy of Peroxisome Proliferator-Activated Receptor (PPAR) Agonists in the Treatment of Primary Biliary Cholangitis: A Meta-Analysis of Randomized Controlled Trials

Introduction: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease marked by progressive bile duct destruction. While ursodeoxycholic acid (UDCA) is first-line therapy, approximately 40% of patients show an incomplete response. Peroxisome proliferator-activated receptor (PPAR) agonists have emerged as promising agents due to their anti-inflammatory and metabolic effects. This meta-analysis evaluates the efficacy of PPAR agonists in improving liver biochemical markers in PBC. Methods: A systematic search of MEDLINE, Embase, and Scopus was performed to identify randomized controlled trials (RCTs) comparing PPAR agonists to placebo in patients with PBC. Eligible studies (1) were placebo-controlled RCTs, (2) included patients with PBC regardless of disease stage or PPAR agonist dose, and (3) reported pre- and post-treatment values for alkaline phosphatase (ALP), bilirubin, and gamma-glutamyl transferase (GGT). Exclusion criteria included studies without a placebo or control group, non-human studies, trials with no relevant outcomes, and trials with incomplete or withdrawn data. Six trials met these criteria. Follow-up durations ranged from 3 to 24 months. To account for variability in treatment effect due to time, we used post-minus-pre-treatment mean differences and a random-effects model. Standard errors were derived using an assumed correlation coefficient (r = 0.7) between paired values. Pooled estimates were weighted by inverse variance and calculated separately for each biomarker. Results: PPAR agonists were associated with significant reductions in liver biomarkers compared to placebo. ALP decreased by –87.14 U/L (95% CI: –90.20, –84.08). Bilirubin declined by –1.04 mg/dL (95% CI: –1.37, –0.71). GGT was reduced by –46.90 U/L (95% CI: –51.64, –42.16). All reductions were statistically significant. Conclusion: In placebo-controlled trials, PPAR agonists significantly improved ALP, bilirubin, and GGT levels in patients with PBC. These findings support their potential role as effective adjunctive therapy, particularly for patients with inadequate response to UDCA.