Alagille syndrome (ALGS) is a multisystem disorder that manifests as childhood cholestasis. Reports of liver transplantation (LT) for patients with ALGS have come largely from single centers, which have reported survival rates of 57% to 79%. The aim of this study was to determine LT outcomes for patients with ALGS. We performed a retrospective analysis of the Studies of Pediatric Liver Transplantation database, which contains information about 3153 pediatric LT recipients. Data were available for 91 patients with ALGS and for 236 age-matched patients with biliary atresia (BA). The frequency of complex cardiac anomalies was lower in the LT group with ALGS versus published ALGS series (5% versus 13%). The pretransplant glomerular filtration rate (GFR) was <90 mL/minute/1.73 m 2 in 18% of the LT patients with ALGS and in 5% of the LT patients with BA (P < 0.001). The height deficit at listing was worse for the ALGS patients (66%) versus the BA patients (22%). The 1-year patient survival rates were 87% for the ALGS patients and 96% for the BA patients (P ¼ 0.002). The deaths in the ALGS group mostly occurred within the first 30 days. No pretransplant factors associated with death were identified in the ALGS group. A survival analysis revealed that biliary (P ¼ 0.02), vascular (P < 0.001), central nervous system (CNS; P < 0.001), and renal complications (P < 0.001) after LT were associated with death in the ALGS group. Renal insufficiency in the ALGS patients worsened after LT, and at 1 year, GFR was <90 mL/minute/1.73 m 2 in 22% of the LT patients with ALGS but in only 8% of the patients with BA (P ¼ 0.0014). More LT pediatric patients with ALGS either were currently receiving special education (50% versus 30% for BA patients, P ¼ 0.02) or had received special education in the past (60% versus 36%, P ¼ 0.01). Vascular, CNS, and renal complications were increased in the ALGS patients after LT, and this reflected multisystem involvement. Although the 1-year survival rate was modestly lower for the ALGS patients versus the BA patients, the clustering of deaths within the first 30 days is notable and warrants increased vigilance and further investigation. Liver Transpl 18:940-948, 2012. V C 2012 AASLD.

Post transplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality in pediatric recipients of liver transplantation (LT). Objective Describe the incidence of PTLD and symptomatic Epstein Barr virus disease (SEBV) in a large multicenter cohort of children who have undergone LT focused on the risk factors and changes in incidence over time. Methods Prospective determination of SEBV and PTLD in 2283 subjects who had undergone a first LT with at least 1 year of follow up in the Studies of Pediatric Liver Transplantation database. SEBV was defined by specific criteria and PTLD required tissue confirmation. Incidences of SEBV and PTLD were determined by Kaplan Meier. Univariate and multivariate modeling of risk factors were performed using standard methods. Results SEBV occurred in 199, of whom 174 (87.4%) were EBV negative at LT. 75 patients developed PTLD of whom 64 (85.3%) were EBV negative at LT. Of 2048 patients with at least 2 years of follow-up, 8.3% developed SEBV and 2.8% PTLD by the second year post-LT. There was a lower incidence of SEBV (11.3% vs 5.9, p<0.0001) and PTLD (4.2 vs. 1.7, p=0.0011) in 2002-07 compared to 1995-2001. Tacrolimus and cyclosporine trough blood levels in the first year post transplant were significantly lower and fewer children were receiving steroids in 02-07. Era of LT, EBV negative recipient status, younger age, biliary atresia and frequent rejection episodes were associated with an increased risk for SEBV and PTLD in univariate analysis. Age, biliary atresia and EBV recipient status were correlated. In multivariate analysis era of LT, EBV recipient status and frequent rejection episodes was associated with SEBV and PTLD. Conclusions The incidence of SEBV and PTLD is decreasing in pediatric LT recipients coincident with a reduction in immunosuppression. Younger recipients and those with multiple rejections remain at higher risk for SEBV and PTLD.

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Metabolic diseases are the second largest indication for LT in children after BA. There are limited data on the long-term post-transplant outcome in this unique group of patients. Therefore, our aim was to assess post-liver transplant outcomes and to evaluate risk factors for mortality and graft loss in children with metabolic disorders in comparison to those with non-metabolic diagnoses. We reviewed all patients enrolled in the SPLIT registry. Between 1995 and 2008, 446 of 2997 (14.9%) children enrolled in SPLIT underwent liver transplant for metabolic diseases. One-yr and five-yr patient survival for children with metabolic diseases was 94.6% and 88.9% and for those with other diseases 90.7% and 86.1% (log-rank p = 0.05), respectively. One-yr and five-yr graft survival for children with metabolic disorders was 90.8% and 83.8%, and for those with other diseases 85.4% and 78.0% (log-rank p = 0.005), respectively. Children with metabolic diseases were less likely to experience gastrointestinal complications (5.6% vs. 10.7%, p = 0.001), portal vein thrombosis (2.9% vs. 5.2%, p = 0.04), and reoperations within 30 days post-transplant (33.4% vs. 37.8%, p = 0.05) than those with other indications. In conclusion, children who underwent liver transplant for metabolic disease had similarly excellent patient survival as, and better graft survival than, those who received a liver allograft for other indications.

Pediatrics, Children's Memorial Hospital, Chicago, IL School performance is an important aspect of functional outcomes for pediatric liver transplant (LT) recipients. This longitudinal analysis conducted through the Studies of Pediatric Liver Transplantation (SPLIT) research consortium examines several indicators of school function in these patients. A total of 39 centers participated in data collection using a semistructured questionnaire designed specifically for this study. The survey queried school attendance, performance and educational outcomes including the need for special educational services. Participants included 823 of 1133 (73%) eligible patients, mean age 11.34 6 3.84 years, 53% female, median age at LT 4.6 (range 0.05-17.8) years, and mean interval from transplant was 5.42 6 2.79. Overall, 34% of patients were receiving special educational services and 20% had repeated a grade, with older participants more likely to have been held back (P ¼ 0.0007). Missing more than 10 days of school per year was reported by one-third of the group, with this level of absence being more common in older participants (P ¼ 0.0024) and children with shorter intervals from LT (P < 0.0001). Multivariate analysis revealed the following factors were associated with the need for special educational services; type of immunosuppression at 6 months post-LT, cyclosporine A (odds ratio [OR] ¼ 1.8, confidence interval [CI] ¼ 1.1-3.1), or other (OR ¼ 4.9, 95% CI ¼ 1.4-17.6) versus tacrolimus, symptomatic cytomegalovirus infection within 6 months of liver transplantation (OR ¼ 3.1, CI ¼ 1.6-6.1), and pretransplant special educational services (OR ¼ 22.5, CI ¼ 8.6-58.4).