Orthotopic liver transplantation for children with Alagille syndrome AGS, syndromatic paucity of intrahepatic bile ducts, is an autosomal dominant, multisystem disorder that primarily affects the liver, heart, eyes, face, and skeleton (1, 2). It occurs in approximately one in 70 000 live births based on the presence of neonatal cholestasis (3). However, this may be an underestimate as molecular testing has demonstrated that many individuals with a disease-causing mutation do not have neonatal liver disease (4). The first reports underestimated the clinical significance of liver disease in children with AGS. It was considered a ‘‘benign’’ syndrome of intrahepatic cholestasis, liver complications were considered responsible for death in 5% of patients and considered to be ‘‘rare’’ indications for LT (5). Over the past 20 yr, there have been reports suggesting that the severity of liver involvement may be higher than originally estimated with liver failure and/or hepatocellular carcinoma occurring in children as young as two to four yr (6). Treatment of AGS depends on the distribution and the severity of the clinical symptoms and the outcome is related to the extent of the hepatic and extrahepatic disease (7). The majority of AGS can be treated conserva- tively with optimization of nutrition, supplemen- tation of fat soluble vitamins, or drugs to relieve the severe pruritus. Biliary diversion and ileal exclusion can be helpful in some patients for refractory pruritus and xanthomas (8–12). It is difficult to establish clear criteria for LT in children with AGS because of the wide variety of clinical symptoms and the multisystem involve- ment. Historically, LT has been performed in patients with AGS for refractory pruritus, xan- thomas, and complications of end stage chole- static liver disease (7, 13). Only small, single- center studies reported the outcomes of LT of patients with AGS (13–15). Arnon R, Annunziato R, Miloh T, Suchy F, Sakworawich A, Hiroshi S, Kishore I, Kerkar N. Orthotopic liver transplantation for children with Alagille syndrome. Pediatr Transplantation 2010: 14: 622–628. Ó 2010 John Wiley & Sons A/S. Abstract: AGS is an inherited disorder involving the liver, heart, eyes, face, and skeleton. Aim: To determine the outcome of LT in children with AGS compared to those with BA. Methods: Children with AGS and BA who had a LT between 10/1987 and 5/2008 were identified from the UNOS database. Results: Of 11 467 children who received a liver transplant, 461 (4.0%) had AGS and 3056 (26.7%) had BA. One- and five-yr patient survival was significantly lower in patients with AGS in comparison with patients with BA (AGS; 82.9%, 78.4%, BA; 89.9%, 84%, respectively). Early death (<30 days from transplant) was sig- nificantly higher in AGS than in BA. One- and five-yr graft survival was significantly lower in AGS than in BA (AGS; 74.7%, 61.5%, BA; 81.6%, 70.0%, respectively). Death from graft failure, neurological, and cardiac complications was significantly higher in patients with AGS than in patients with BA. Serum creatinine at transplant, prior LT, and cold ischemic time >12 h were identified as risk factors for death. Conclu- sion: Children with AGS were older at the time of LT and their one- and five-yr patient and graft survival were significantly lower compared to BA. Risk factors for poor outcome in AGS after LT were identified. Ronen Arnon 1,2 , Rachel Annunziato 3 , Tamir Miloh 1,2 , Frederick Suchy 1 , Arnond Sakworawich 3 , Sogawa Hiroshi 1,2 , Iyer Kishore 1,2 and Nanda Kerkar 1,2 1 Pediatrics and 2 Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY, USA, 3 Fordham University, New York, NY, USA Key words: biliary – cholestasis – end-stage liver disease – liver transplantation – outcome – pediatric Ronen Arnon, Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1104, New York, NY 10029, USA Tel.: +212 659 8060 Fax: +212 241 2064 E-mail: Ronen.Arnon@mountsinai.org Accepted for publication 28 October 2009 Abbreviations: AGS, Alagille syndrome; BA, biliary atre- sia; BMI, body mass index; CLIC, cholestatic liver disease consortium; DCD, donation after cardiac death; INR, in- ternational normalized ratio; LT, liver transplantation; MELD, model end-stage liver disease; PELD, pediatric end- stage liver disease; SPLIT, studies of pediatric liver trans- plantation; UNOS, United Network for Organ Sharing. Pediatr Transplantation 2010: 14: 622–628 Ó 2010 John Wiley & Sons A/S. Pediatric Transplantation DOI: 10.1111/j.1399-3046.2009.01286.x 622