Journal Article

P219 Efficacy and safety of peroxisome proliferator-activated receptor agonists in primary biliary cholangitis: a systematic review and meta-analysis

Jawad Zahid, Tagwa Kalool Fadlalla Ahmad, Dhali, Arkadeep, Aimen Waqar Khan, Fabiha Athar, Affan, Muhammad, Ali, Saqib, Haziq Ovais, Tooba Fatima, Samra Ishaq, Rayamajhi, Sushil, Gaur, Aditya, Yusra Muhammad Saleem, Noor ul Ain, Syeda Dua Azhar, Dushyant Singh Dahiya, Rehman, Zuhaa, Bharadwaj, Hareesha Rishab, Marrium Sultan Dar, Muhtasim Fuad

2025

Overview

BackgroundPrimary Biliary Cholangitis (PBC) is a rare autoimmune liver disease that causes liver inflammation and damage, potentially leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the standard treatment, but up to 40% of patients are non-responders. Due to the limited treatment options, there is a need to explore alternative therapies. This study evaluates the efficacy and safety of PPAR agonists for PBC management.MethodsA systematic review and meta-analysis were performed, including eight randomized controlled trials (RCTs) evaluating selective PPAR agonists (fenofibrate, seladelpar) and multi-subtype PPAR agonists (bezafibrate, saroglitazar, elafibranor). The primary outcome was alkaline phosphatase (ALP), while secondary outcomes included GGT, ALT, AST, total bilirubin (TBil), triglycerides (Tg), and pruritus. Subgroup analyses were conducted based on the type of PPAR agonists used in the trials.ResultsThe analysis revealed that PPAR agonists significantly reduced ALP levels compared to placebo (SMD = -0.66, p = 0.0005), indicating a notable improvement in liver function. Similarly, there was a significant reduction in GGT levels (SMD = -0.45, p = 0.02), which is a marker of liver injury and cholestasis. The overall reduction in total bilirubin (TBil) was also significant (SMD = -0.77, p = 0.006), suggesting improved biliary function. Triglyceride levels showed a significant decrease with PPAR agonists (MD = -0.99, p = 0.003), consistent with the lipid-regulating effects of PPAR activation. However, no significant changes were found for ALT (p = 0.07) or AST (p = 0.99), indicating that PPAR agonists may not significantly impact these liver enzymes in PBC. Subgroup analysis demonstrated that both selective PPAR agonists (such as fenofibrate and seladelpar) and multi-subtype PPAR agonists (like bezafibrate and elafibranor) led to significant reductions in ALP and GGT compared to placebo. Interestingly, selective PPAR agonists exhibited minimal heterogeneity for TBil levels (I² = 0%), while multi-subtype agonists maintained high heterogeneity. The analysis of pruritus found no significant difference between PPAR agonists and placebo (p = 0.6), despite some trials reporting variable effects on pruritus severity.Abstract P219 Figure 1Forest plot of change in ALP levels from baseline[Figure omitted. See PDF]ConclusionPPAR agonists are effective in reducing key biochemical markers of liver dysfunction in PBC, particularly ALP, GGT, TBil, and triglycerides. However, their effect on ALT, AST, and pruritus remains limited. Further studies with larger sample sizes and longer durations are required to fully explore the therapeutic potential of PPAR agonists in managing PBC.

• Publisher: BMJ Publishing Group LTD
• Subject: Agonists / Alkaline phosphatase / Bezafibrate / Bilirubin / Biochemical markers / Cholangitis / Cholestasis / Cirrhosis / Clinical trials / Fenofibrate / Liver / Liver diseases / Liver failure / Meta-analysis / Peroxisome proliferator-activated receptors / Placebos / Pruritus / Systematic review / Triglycerides / Ursodeoxycholic acid