Cholestasis-reducing effects of bezafibrate on survivors of biliary atresia with native livers: A prospective phase II trial

BACKGROUND: Long-term survivors of biliary atresia (BA) require liver transplantation owing to cholestasis-associated complications. Bezafibrate (BZF), an antihyperlipidemic agent, can improve cholestasis-induced liver damage. Herein, we evaluated the cholestasis-reducing effect of BZF on survivors of BA with native livers, a condition that has not been previously assessed in any study. METHODS: In this single-center, single-arm, open-label, uncontrolled, prospective phase II trial, patients were enrolled from a central registry system at the Chiba University Data Center. Postoperative patients (n=10) aged older than 18 years (median age, 29 y) with BA and increased serum ALP levels were enrolled between July 2021 and March 2022. Patients with high total bilirubin or alanine aminotransferase levels, recent changes in BA medication, cholangitis within 3 months, renal dysfunction, or liver transplantation were excluded. Participants were administered 400 mg BZF orally in 2 daily doses for 12 weeks and subsequently underwent a 12-week observation. Other drugs were continued. The primary endpoint was the change in ALP levels after 12 weeks of oral BZF administration. The secondary and exploratory endpoints were changes in gamma-glutamyl transpeptidase and triglyceride levels, fecal microbiota, and bile acids. RESULTS: The mean change in the ALP level was -67 U/L (±20 U/L; p=0.0042). Changes in ALP and gamma-glutamyl transpeptidase levels differed between week 0 and week 6. Adverse events occurred in 5 patients. BZF administration increased the number of Fusicatenibacter without affecting microbiome diversity or bacterial phylum abundance while decreasing lithocholic acid levels and increasing chenodeoxycholic acid levels. CONCLUSIONS: BZF decreased cholestasis markers in survivors of BA with native livers, indicating its potential as an alternative to delayed liver transplantation for this population.