Fenofibrate improves GLOBE and UK-PBC scores and histological features in primary biliary cholangitis.

Abstract

Fenofibrate (FF) has been suggested as a second-line therapy for primary biliary cholangitis (PBC) with suboptimal response to ursodeoxycholic acid (UDCA). But its long-term effect is unclear. From a retrospective cohort (N.=838), we enrolled 106 UDCA-refractory PBC patients, among them 62 received UDCA monotherapy (UDCA group) and 44 received FF combined with UDCA (UDCA+FF group). Changes of liver biochemistries and prognosis after treatment were determined. In addition, sequential liver biopsies were used to assess the effect of FF on histological parameters. We found adding FF could significantly reduce serum levels of alkaline phosphatase (ALP), but for patients with pretreatment ALP≥1.67 upper limit of normal (ULN), the significant decline of serum ALP was only observed in the UDCA+FF group after 1 year of therapy. The mean GLOBE Score and the liver transplant-free survival predicted by GLOBE Score were both improved significantly in patients receiving UDCA+FF after 1 year of therapy. The liver-related death or liver transplant calculated using UK-PBC risk score was significantly reduced in patients receiving UDCA+FF after 1 year of therapy. Although there was no marked difference in the final histological analysis after 3 years of therapy, patients receiving UDCA+FF had improvements or stabilization in fibrosis (85.7%), and bile duct loss (78.6%) were more than that of patients receiving UDCA (70.6% and 76.5%, respectively). Adding FF improves GLOBE and UK-PBC scores and is also associated with the improvements or stabilization of disease features, including fibrosis and ductular injury.