Long-Term Outcomes of Fenofibrate for Treatment of Ischemic Cholangiopathy in Donation After Circulatory Death Liver Transplantation.

The incidence of ischemic cholangiopathy (IC) is expected to remain significant due to rising rates of transplants performed with livers donated after circulatory death (DCD), despite the use of machine perfusion. Absent established pharmacologic interventions against this progressive etiology of allograft dysfunction and failure, we describe the use of fenofibrate-a cheap and widely-accessible peroxisome proliferator-activated receptor agonist that downregulates bile acid production-to impede IC progression in 15 DCD liver recipients who were not responding to reactive, standard-of-care management. All patients were undergoing serial endoscopic retrograde cholangiopathy (ERC) to maintain biliary patency but demonstrated progressive cholestasis, with serum alkaline phosphatase (ALP) rising 70.3% over the 90 days preceding fenofibrate. Cholestasis improved in all patients after fenofibrate initiation, with a 63.9% reduction in mean ALP at 90 days, maintained at 270 days (p = 0.02) and 360 days (p = 0.06). ALP improvement was associated with reduced ERC frequency during and after fenofibrate treatment, and this improvement was independent of concurrent ERC or ursodeoxycholic acid use during fenofibrate treatment. In patients who stopped treatment, ALP increased. No fenofibrate-associated adverse events were seen. These preliminary data support the further study of agents that downregulate bile acid production as a means of impeding IC in DCD livers.