Additional fibrate treatment in UDCA‐refractory PBC patients

• Published in: Liver international Vol. 39; no. 9; pp. 1776 - 1785
• Main Authors: Chung, Sung Won, Lee, Jeong‐Hoon, Kim, Minseok Albert, Leem, Galam, Kim, Sun Woong, Chang, Young, Lee, Hyo Young, Yoon, Jun Sik, Park, Jun Yong, Lee, Yun Bin, Cho, Eun Ju, Yu, Su Jong, Kim, Yoon Jun, Yoon, Jung‐Hwan
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.09.2019
• Subjects: Alkaline phosphatase; ALP normalization; Bezafibrate; Cholangitis; Cirrhosis; Confidence intervals; Deterioration; Fenofibrate; Liver cirrhosis; Long-term effects; Patients; primary biliary cholangitis; Statistical analysis; Ursodeoxycholic acid; bezafibrate; fenofibrate; ALP normalization; cirrhosis; primary biliary cholangitis
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.14165

Background & Aims There is no proven treatment for ursodeoxycholic acid (UDCA)‐refractory primary biliary cholangitis (PBC) other than obeticholic acid. Although fibrates have been reported to improve biochemical parameters, the long‐term effects remain unclear. This study evaluated the effect of fibrate on clinical outcomes of UDCA‐refractory PBC. Methods Patients whose alkaline phosphatase (ALP) was not normalized with at least 13 mg/kg of UDCA treatment for >1 year were included from two tertiary referral centres. The primary outcome was ALP normalization. Secondary outcomes included the development of cirrhosis and hepatic deterioration. Immortal time bias was adjusted using the Mantel‐Byar method. Results A total of 100 UDCA‐refractory PBC patients were included: 71 patients received UDCA alone (the UDCA group) and 29 patients received UDCA plus additional fibrate treatment of 160 mg/d fenofibrate or 400 mg/d bezafibrate (the fibrate/UDCA group). During the follow‐up period, the probability of ALP normalization was significantly higher in the fibrate/UDCA group (hazard ratio [HR] = 5.00, 95% confidence interval = 2.87‐8.27, P < 0.001). Among 58 non‐cirrhotic patients (43 in the UDCA group and 15 in the fibrate/UDCA group), 19 patients (44.1%) in the UDCA group and none in the fibrate/UDCA group developed cirrhosis (HR = 0.12, P = 0.04). Hepatic deterioration (Child‐Pugh score increase or signs of decompensated cirrhosis) occurred in 17 patients (23.9%) of the UDCA group and none in the fibrate/UDCA group in which the difference was significant (HR = 0.12, P = 0.04). Conclusions In patients with UDCA‐refractory PBC, additional fibrate treatment is associated with a higher probability of ALP normalization and a lower risk of cirrhosis development and hepatic deterioration.