Long-term add-on fibrate therapy in Primary Sclerosing Cholangitis: Safety, biochemical response, and disease progression.

BACKGROUND AND AIMS: Fibrates may improve cholestasis and pruritus in Primary Sclerosing Cholangitis (PSC), but long-term data is limited. This study assessed the safety and biochemical, radiological, and clinical effects of fibrates in PSC.

METHOD: We retrospectively analysed PSC patients on stable UDCA therapy who received add-on fibrates between 2017 and 2025. Clinical, biochemical, radiological, and elastography data were collected to assess treatment response, safety, and disease progression.

RESULTS

Of 37 PSC patients initiating fibrates, 34 were included, 21% with cirrhosis. Fenofibrate was used in 88% for a median of 34 months. Significant reductions in ALP, GGT, and ALT were observed at 6 months and sustained over follow-up. The proportion of patients with ALP < 1.5 × ULN increased from 22% to 45% at 6 months. The Amsterdam-Oxford score (AOM) decreased significantly at 6 and 12 months (p = 0.02). Responders had lower baseline bilirubin, transaminases, AOM, and Mayo Risk score (p < 0.05). Pruritus improved while fatigue, cholangitis frequence, and liver stiffness remain unchanged. MRI follow-up showed worsening of ANALI score due to bile duct dilatation, with stable DiStrict score. Adverse events occurred in 15%, leading to discontinuation in 4 patients.

CONCLUSION

Fibrates appear to be a safe and potentially effective option in PSC, especially in early-stage disease, pending confirmation from prospective trials.