Bezafibrate therapy in primary biliary cholangitis refractory to ursodeoxycholic acid: a longitudinal study of paired liver biopsies at 5 years of follow up

• Published in: Alimentary pharmacology & therapeutics Vol. 54; no. 9; pp. 1202 - 1212
• Main Authors: Sorda, Juan Antonio, González Ballerga, Esteban, Barreyro, Fernando Javier, Avagnina, Alejandra, Carballo, Pilar, Paes de Lima, Andrea, Daruich, Jorge
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2021
• Subjects: Bezafibrate; Bezafibrate - therapeutic use; Biopsy; Cholagogues and Choleretics - therapeutic use; Cholangitis; Cirrhosis; Clinical trials; Drug Therapy, Combination; Fibrosis; Follow-Up Studies; Humans; Inflammation; Liver; Liver cirrhosis; Liver Cirrhosis, Biliary - drug therapy; Longitudinal Studies; Patients; Ursodeoxycholic acid; Ursodeoxycholic Acid - therapeutic use
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.16618

Summary Background Ursodeoxycholic acid (UDCA) is the first‐line therapy for primary biliary cholangitis (PBC). However, nearly 40% of patients have an incomplete response to UDCA. The addition of bezafibrate has shown biochemical benefit in this group of patients. Aim To evaluate the long‐term effects of UDCA in combination with bezafibrate on histological outcomes in patients with UDCA‐refractory PBC. Methods Fifty‐nine patients refractory to UDCA were included. Clinical parameters were monitored and paired liver biopsy (PLB) was performed after 5 years of follow‐up. Results Of the total cohort, 49 subjects were analysed and 31 had PLB at 5 years. Values for serum ALP, AST, ALT and GGT significantly improved with UDCA‐bezafibrate. This beneficial effect was observed at 12 months where 86% achieved ALP at normal levels. Analyses of PLB showed a significant decrease in liver damage as reflected by Ludwig (baseline 2.29 ± 1.2, to 1.84 ± 1 at year 5, P = 0.0242) and Ishak (baseline 6.19 ± 2.2 to 4.77 ± 2.2 at year 5, P = 0.0008) scores. Overall, regression of fibrosis was attained in 48% of patients. Furthermore, we observed a significant reduction in the proportion with cirrhosis from 19% at baseline to 3% at 5 years (P < 0.001). These beneficial effects were associated with better predictive risk scores using the GLOBE and UK‐PBC prognosis models. Conclusions Adding bezafibrate to UDCA in patients with UDCA‐refractory PBC showed a significant decrease in fibrosis and inflammatory histological scores at 5 years. These beneficial effects warrant further evaluation in long‐term cohort studies and controlled trials. Ranked Assessment of Necroinflammatory Activity and Fibrosis.