- 2026-05-25
- Frontiers in pharmacology 17
Study Design
- Type
- Systematic Review
- Sample size
- n = 276
- Population
- Patients with primary biliary cholangitis (PBC)
- Methods
- Systematic review of meta-analyses evaluating fibrates, alone or in combination with UDCA; databases searched from inception to 2025
Background
Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by progressive cholestasis. Although ursodeoxycholic acid (UDCA) is the standard therapy, a substantial proportion of patients show inadequate response, highlighting the need for alternative or adjunct treatments. Fibrates have emerged as adjunct agents to UDCA, but evidence remains inconsistent across trials and meta-analyses.Methods
We conducted a systematic review of meta-analyses evaluating fibrates, alone or in combination with UDCA, in PBC patients. Databases were searched from inception to 2025. Primary outcomes included biochemical response (alkaline phosphatase [ALP] and bilirubin), treatment response rates, and adverse events. Overlap among meta-analyses was assessed using the corrected covered area (CCA), and methodological quality was evaluated with AMSTAR 2.Results
Twenty-three meta-analyses were included, encompassing 45 unique randomized controlled trials (RCTs) with a total of 3,276 patients after removing duplicate RCTs across meta-analyses. Combination therapy of fibrates with UDCA significantly improved biochemical outcomes compared with UDCA alone (ALP: MD -85.4 U/L, 95% CI -102.7 to -68.1; bilirubin: MD -0.45 mg/dL, 95% CI -0.62 to -0.28). Biochemical response rates were higher with combination therapy (RR 1.42, 95% CI 1.25-1.61). Fibrate monotherapy showed moderate improvements in ALP (MD -48.7 U/L, 95% CI -67.5 to -29.9) and bilirubin (MD -0.23 mg/dL, 95% CI -0.39 to -0.07). Adverse events occurred in 12%-18%, mostly mild pruritus and gastrointestinal symptoms. Overlap between meta-analyses was high (CCA = 11%), and methodological quality ranged from moderate to high.Conclusion
This umbrella meta-analysis provides the most comprehensive synthesis to date, supporting UDCA-fibrate combination therapy for biochemical response in PBC. However, evidence on survival and transplant-free outcomes remains insufficient.