Odevixibat therapy in patients with FIC1-deficient progressive familial intrahepatic cholestasis and severe diarrhoea following liver transplantation: a retrospective case series

Introduction Features of progressive familial intrahepatic cholestasis due to deficiency in FIC1 (encoded by ATP8B1; PFIC1) may include disrupted bile acid handling, pruritus, poor growth, other extrahepatic manifestations, and progressive liver disease that can necessitate liver transplantation (LT). While certain symptoms of PFIC1 may resolve after LT, patients frequently have persistent malabsorption, diarrhoea, and failure to thrive that can impact quality of life. In this case series, we present clinical details of 3 patients with PFIC1 and post-LT diarrhoea that impacted daily activities who received odevixibat, an ileal bile acid transporter inhibitor, in clinical practice. Methods Retrospective patient data were collected by treating physicians using standardised forms and included demographic, clinical, and treatment information. Results Data from 3 male patients with post-LT diarrhoea were collected. Prior to LT, patient symptoms included cholestasis, elevated serum bile acids, pruritus, dystrophy, and/or vitamin deficiencies. Patients experienced symptoms ranging from 1.8 to 4.8 years before LT and had unsatisfactory responses to conventional medical therapies. All patients underwent split LT, and common indications for LT included cholestasis, dystrophy, and intractable pruritus. After LT and prior to odevixibat initiation, patients had steatosis (patients 2 and 3), inflammation (patient 3), and diarrhoea (all patients). Patient 3 underwent surgical biliary diversion at 4 years post-LT, which resolved the steatosis and inflammation. Post-LT diarrhoea impacted the daily life and/or school functioning of all patients. Attempts to treat the diarrhoea with cholestyramine (patients 2 and 3) and Oralpädon (patients 1 and 2) were unsuccessful, with unresolved diarrhoea as the reason physicians cited for initiating odevixibat. After odevixibat initiation, patients had less-frequent and/or firmer stools at last available assessment, as well as improvements in aspects of daily life. Conclusions In patients with FIC1 deficiency, chologenic diarrhoea after LT, which may be due to physiologic bile acid levels in the FIC1-deficient bowel, can be a frequent and severe symptom. The real-world data presented here indicate that odevixibat can improve diarrhoea and quality of life in patients with PFIC1 and severe post-LT diarrhoea.