Estella M. Alonso

Limbers CA, Neighbors K, Martz K, Bucuvalas JC, Webb T, Varni JW, Alonso EM, on behalf of the Studies of Pediatric Liver Transplantation (SPLIT) Functional Outcomes Group (FOG). Health‐related quality of life in pediatric liver transplant recipients compared with other chronic disease groups. Pediatr Transplantation 2011: 15: 245–253. © 2010 John Wiley & Sons A/S.Abstract:  This cross‐sectional, multicenter cohort study compares the level of HRQOL of pediatric LT recipients to children with other chronic health conditions. LT sample included 873 children who survived at least 12 months following LT. Six chronic disease samples were compiled from numerous studies, including over 800 patients with JRA, type 1 diabetes, cancer in remission, cardiac disease, end‐stage renal disease, and inflammatory bowel disease. Generic HRQOL was measured from both the parental and patient perspective using the PedsQL™ 4.0 Generic Core Scales. Pediatric LT patients reported better physical health than children with JRA. According to parents, pediatric LT recipients had better HRQOL than children on renal dialysis on all domains except school functioning. Across all domains but emotional functioning, pediatric LT recipients reported significantly lower HRQOL than children with type 1 diabetes. Overall, pediatric LT patients reported HRQOL comparable to that of children who had undergone renal transplantation and patients with cancer in remission. Pediatric LT patients manifested impaired HRQOL similar to that of children with chronic diseases and these data suggest that they face ongoing challenges that warrant monitoring and indicate a need for interventions to improve their HRQOL.

This multicenter study compared health-related quality of life (HRQOL) and family function of pediatric liver transplant recipients to those of healthy children to determine if this population differed from a healthy population and to distinguish which pretransplant and posttransplant factors impact HRQOL and family function. HRQOL data from 102 patients achieving 2-year survival were collected with the Infant Toddler Quality of Life Instrument or the Child Health Questionnaire Parent Form 50 parent surveys. Family functioning was assessed with the Family Assessment Device (FAD) completed by each participant's family members. Demographic and clinical information were retrieved from the Studies of Pediatric Liver Transplant database. Recipients 5 years of age and older scored lower than a normative sample in physical health ( P < 0.001), general health ( P < 0.001), parental emotional impact ( P < 0.001), and disruption of family activities ( P < 0.001). Younger children, 2 to 5 years of age, scored lower than controls in global health ( P = 0.004) and general health perceptions ( P < 0.001) but did not differ in subscales measuring physical and psychosocial outcomes. Univariate analysis among the subscales identified demographic but not clinical variables as significant predictors of HRQOL. Mean scores of FAD scales were below published thresholds indicating healthy family functioning. As reported in previous studies, parents of older recipients reported higher levels of stress, although their level of family function appears normal. Significant associations were also observed between FAD scores and demographic variables, suggesting that further investigation of the impact of race, parental marital status, and socio-economic status on the patient rehabilitation process is needed.

Over the past 5 years, we have employed several strategies to increase the donor pool for both the pediatric and adult populations. The innovative expansion of the donor pool with the use living-related donors for children and cadaveric, high-risk donors for adults has increased our ability to serve our recipients and transplant them at an earlier stage in the disease process, thereby improving survival. As Hepatitis C is now the leading indication for liver transplantation in the adult population, the investigation of the natural history of Hepatitis C prior to and after transplantation provides a major challenge and is currently a focus of both laboratory and clinical efforts. For those recipients of Hepatitis C-positive-donor livers, determining the role of recipient and donor genotypes in the progression of recurrent hepatitis should help define the proper utilization of these organs. For patients on CsA-based immunosuppression regimens who experience steroid-resistant rejection, tacrolimus has proved to be extremely effective in reversing the rejection episodes and maintaining normal graft function. The long-term results of this therapy appear to be superior to OKT3 therapy. The recipients of living-related liver transplantation continue to have a survival advantage in comparison to recipients of cadaveric grafts. The donor operation can be routinely performed with minimal risk. Because of the superior results achieved and minimal donor risks, we feel that providing the option of living-donor transplantation is ethically justified, and medically necessary. Despite the encouraging results from living-donor transplantation, unexpected complications including portal vein complications and hepatic artery thrombosis have forced technical modifications of the original technique which may have implications to pediatric liver transplantation in general. As the volume of pediatric liver transplants and the number of immmunosuppressive regimens have increased over the years, posttransplant lymphoproliferative disease has been identified as a problem which requires more inspection. We have determined that the severity of rejection and the subsequent treatment, and primary Epstein-Barr virus are the primary risk factors for developing of PTLD. Identification of the risk factors and early detection may provide some hope for treatment of the disease while allowing long-term graft function. Results of our preliminary data show that, following transplantation, 3/4 of the children or parents report minimal impairment with regard to developmental or physical milestones. Patients and their families, however, continue to report significant levels of stress in their lives and occasional pain. Further research on outcome needs to be performed on our pediatric recipients to ensure the long-term benefit of our efforts.

The concept of graft-reduction surgery in liver transplantation has revolutionized pediatric transplantation and soon may carry over into adult transplantation. Reduced-size liver transplants have virtually eliminated patient deaths while waiting for donor organs to become available by increasing the potential donor pool. This has shifted the distribution of pediatric liver transplant recipients to a younger age which more closely matches the needs of pediatric patients with end-stage liver disease. Split-liver transplants can create new grafts without increasing the donor supply. Living-donor liver transplantation not only increases the supply of organs but also creates uniformly good quality grafts that can be used electively in stable patients. The result is patient and graft survival rates that are better than those seen with cadaveric organs. Orthotopic auxiliary liver transplantation offers children with metabolic disorders the opportunity to correct their diseases without the risks associated with whole-organ replacement.