LONG-TERM OUTCOMES OF PEDIATRIC LIVER TRANSPLANTATION FOR PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS

Abstract

Introduction: Progressive familial intrahepatic cholestasis (PFIC) is a rare group of heterogenous autosomal recessive disorders characterized by defective bile acid secretion or transportation leading to progressive cholestasis. The different types of PFIC are associated with varying genetic defects leading to different phenotypes and extrahepatic manifestations. We report our experience with liver transplantation (LT) in eighteen PFIC patients. Methods: We performed a retrospective review of all children less than 18 years old who underwent LT with a diagnosis of PFIC at our institution. Genetic mutation analysis and explant histopathology were used to confirm all diagnoses. Patient demographics, clinical and laboratory studies, and perioperative data including impact of LT on growth were analyzed. Results: Eighteen children with PFIC underwent LT between November 2005 and October 2018. (Table 1) Subtype analysis based on genetic testing and pathology included two PFIC type 1 (PFIC1), ten PFIC type 2 (PFIC2), two PFIC type 3 (PFIC3), two PFIC type 4 (PFIC4), and two PFIC type 5 (PFIC5). Median age at time of liver transplant was one year of age with the youngest transplant performed on a three-month-old and the oldest transplant performed on a 17-year-old. Two patients with PFIC1 had prior internal cholecystojejunocolostomies for biliary diversion. Two patients, both with PFIC2, had prior partial external biliary diversion procedures. Follow-up from time of transplant ranged from 2 to 15 years, with a median of 8 years. There was improvement in growth in terms of height and weight across all PFIC subtypes. Overall mean height z-score improved from -1.89 to -0.84. Mean weight z-score improved from -1.15 to 0.16. Overall median total bilirubin before transplantation was 7.5 mg/dL with normalization to 0.5 mg/dL posttransplant. There have been no graft failures or deaths in our population. Conclusion: LT is a safe and effective long-term treatment for PFIC of all subtypes. It is associated with good outcomes in terms of growth and control of cholestasis as measured in total bilirubin. There is little morbidity in our population with 100% graft and patient survival even after fifteen years of follow-up.