Fenofibrate in Primary Biliary Cholangitis Patients with Inadequate Response to Ursodeoxycholic Acid (UDCA)

Introduction: Primary biliary cholangitis (PBC), is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been firstline treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. THE AIM: of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor alpha, in PBC patients with incomplete response to UDCA. Methods: Patients with PBC treated with UDCA were methodically identified in the electronic medical record of a large tertiary care hepatology practice in New York City using an automated query function for keywords PBC and Ursodeoxycholic acid. Results: A total of 91 patients with PBC treated with UDCA (13-15 mg/kg/day) for longer than 12 months were identified. Out of 91 patients, 8 did not have adequate response to UDCA. All eight patients with inadequate response were females, and the mean age was 64 years (range from 46 to 89). Only one patient out of eight had cirrhosis. Alkaline phosphatase (ALP) in these patients ranged from 164U/L to 342U/L. In addition to UDCA, all eight patients were started on Fenofibrate at the doses ranging from 48mg to 160mg daily and were followed for 6-12-month period. Five out of eight patients on combination therapy had complete normalization of ALP. Two out of eight patients on combination therapy achieved biochemical response defined as ALP decrease to ≤1.67x ULN according to Toronto criteria. One patient on combination therapy who had significant decrease of ALP from 342U/L to 220U/L, but failed to achieve biochemical response, was later diagnosed with autoimmune hepatitis/PBC overlap syndrome. No significant adverse effects were observed in patients taking fenofibrate. Conclusion: In patients with PBC refractory to UDCA, fenofibrate is a reasonable choice as an adjunct treatment to UDCA. Further, randomized controlled trials are needed to further evaluate the observed benefits of fibrates in the treatment of PBC.