Decreasing incidence of symptomatic Epstein-Barr virus disease and posttransplant lymphoproliferative disorder in pediatric liver transplant recipients: report of the studies of pediatric liver transplantation experience.

UNLABELLED: Posttransplant 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 (SEBV) disease in a large multicenter cohort of children who underwent LT with a focus on the risk factors and changes in incidence over time. SEBV and PTLD were prospectively determined in 2283 subjects who had undergone LT for the first time with at least 1 year of follow-up in the Studies of Pediatric Liver Transplantation database. SEBV was defined with specific criteria, and PTLD required tissue confirmation. The incidence of SEBV and PTLD was determined with a Kaplan-Meier analysis. Univariate and multivariate modeling of risk factors was performed with standard methods. SEBV occurred in 199 patients; 174 (87.4%) were EBV-negative at LT. Seventy-five patients developed PTLD, and 64 (85.3%) of these patients were EBV-negative at LT. Among the 2048 patients with at least 2 years of follow-up, 8.3% developed SEBV by the second year after LT, and 2.8% developed PTLD. There were lower rates of SEBV (5.9% versus 11.3%, P < 0.001) and PTLD (1.7% versus 4.2%, P = 0.001) in 2002-2007 versus 1995-2001. In 2002-2007, tacrolimus and cyclosporine trough blood levels in the first year after LT were significantly lower, and fewer children were receiving steroids. Biliary atresia, and recipient EBV status were correlated. In a multivariate analysis, era of LT, recipient EBV status, and frequent rejection episodes were associated with SEBV and PTLD. The incidence of SEBV and PTLD is decreasing in pediatric LT recipients concomitantly with a reduction in immunosuppression. Younger recipients and those with multiple rejections remain at higher risk for SEBV and PTLD.

Health status of children alive 10 years after pediatric liver transplantation performed in the US and Canada: report of the studies of pediatric liver transplantation experience.

OBJECTIVES: To determine clinical and health-related quality of life outcomes, and to derive an "ideal" composite profile of children alive 10 years after pediatric liver transplantation (LT) performed in the US and Canada. STUDY DESIGN: This was a multicenter cross-sectional analysis characterizing patients enrolled in the Studies of Pediatric Liver Transplantation database registry who have survived >10 years from LT. RESULTS: A total of 167 10-year survivors were identified, all of whom received daily immunosuppression therapy. Comorbidities associated with the post-LT course included post-transplantation lymphoproliferative disease (in 5% of patients), renal dysfunction (9%), and impaired linear growth (23%). Health-related quality of life, as assessed by the PedsQL 4.0 Generic Core Scales, revealed lower patient self-reported total scale scores for 10-year survivors compared with matched healthy children (77.2±12.9 vs 84.9±11.7; P<.001). At 10 years post-LT, only 32% of patients achieved an ideal profile of a first allograft stable on immunosuppression monotherapy, normal growth, and absence of common immunosuppression-induced sequelae. CONCLUSION: Success after pediatric LT has moved beyond patient survival. Availability of an ideal composite profile at follow-up provides opportunities for patients, families, and healthcare providers to identify broader sets of outcomes at earlier stages, ultimately contributing to improved outcomes after pediatric LT.

Evaluating non-adherence to immunosuppressant medications in pediatric liver transplant recipients.

Non-adherence with recommended immunosuppressant medications is common post-pediatric liver transplant and is the most important reason for organ rejection in long-term survivors. However, there is currently no validated, standard method to measure adherence, with a well-defined threshold, making it extremely difficult to evaluate interventions to improve adherence. Previous studies have suggested that the degree of fluctuation of medication blood levels over time can provide an idea about how regularly the medication is being taken. The present study, conducted at UCLA medical center, sought to identify a specific threshold value of the s.d. of individual tacrolimus blood levels in pediatric liver transplant recipients which would be associated with rejection episodes in these patients. A threshold of 3.0 has been identified in other studies, and was supported by the analysis of retrospective data from 96 subjects. However, further analysis found that a s.d. of 2.5 appeared to have a better fit with the data. These findings suggest the utility of monitoring the s.d. of routine tacrolimus blood levels in pediatric liver transplant recipients for detecting non-adherence to immunosuppressant medication prior to clinical rejection, allowing earlier interventions.

Biliary atresia: clinical profiles, risk factors, and outcomes of 755 patients listed for liver transplantation.

OBJECTIVES: To test the hypothesis that risk analysis from the time of listing for liver transplantation (LT) focuses attention on areas where outcomes can be improved. STUDY DESIGN: Competing outcomes and multivariate models were used to determine significant risk factors for pretransplantation and posttransplantation mortality and graft failure in patients with biliary atresia (BA) listed for LT and enrolled in the Studies of Pediatric Liver Transplantation (SPLIT) registry. RESULTS: Of 755 patients, most were infants (age < 1 year). Significant waiting list mortality risk factors included infancy and pediatric end-stage liver disease (PELD) score > or = 20, whose components were also continuous risk factors. Survival posttransplantation (n=567) was 88% at 3 years. Most deaths were from infection (37%). Posttransplantation mortality risk factors included infant recipients, height/weight < -2 standard deviations (SD), use of cyclosporine versus tacrolimus and retransplantation. Graft failure risks included height/weight < -2 SD, cadaveric partial donors, donor age < or = 5 months, use of cyclosporine versus tacrolimus, and rejection. CONCLUSIONS: Referral for LT should be anticipatory for infants with BA with failed portoenterostomies. Failing nutrition should prompt aggressive support. Post-LT risk factors are mainly nonsurgical, including nutrition, the relative risk of infection over rejection, and the choice of immunosuppression.