Introduction: Alagille syndrome (AGS) is a multisystem disorder in which complications of chronic liver disease and severe pruritus often lead to liver transplantation (LTx). Extrahepatic manifestations, mainly cardiovascular, are significant burden adding risk to the overall outcomes. The aim of this study was to analyze the clinical characteristics and the outcomes of liver transplantation in children with AGS.

Methods: We retrospectively reviewed clinical data of children with AGS who underwent LTx in our hospital. Pre and post-transplant clinical data was collected, particularly systemic manifestations, indications for LTx, early post-transplant complications and long-term patient and graft survival.

Results: Between 1995 and 2022, twenty patients (15 males) underwent LTx. Major indications were severe pruritus, malnutrition with or without growth retardation, synthetic liver failure, portal hypertension, recurrent bone fractures, disfiguring xanthomata and hepatocellular carcinoma. All transplanted patients developed severe cholestasis in the first months of life, five (25%) had a history of Kasai hepatoportoenterostomy for misdiagnosed biliary atresia, 4 (20%) underwent partial external biliary diversion and one (5%) ileal bypass. Median PELD value was 15,1 (range 10-37). Cardiovascular anomalies were present in 17 (85%) of patients, the most common pulmonary stenosis (65%). Median age at LTx was 6.2 years (range 1.5-11.8). In 14 cases living donor LTx was performed and 6 from deceased donor. Four patients received liver from AB0 incompatible donor. Early post-transplant period was complicated with portal vein stenosis in 3 and hepatic artery thrombosis in 2 patients. One patient was deceased as a result of intra-abdominal hemorrhage. Median post-transplant follow-up was 11.1 years (1.9-15.8) and overall patient survival was 94%. There was significant catch-up growth and weight gain in presented group. Currently all patients present with normal graft function and no significant extrahepatic complications.  No serious cardiovascular events were reported. Protocol biopsies 3-8 years post-transplant were performed in 13 patients and showed normal or mild fibrosis in 77% and moderate fibrosis in 23%. 

Conclusion: Liver transplantation including living-related donors is safe and effective in AGS. Multidisciplinary approach at the time of listing is mandatory, with special focus on cardiovascular disorders, renal function and nutrition.