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.