Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.