Long-Term Functional Recovery and Quality of Life

Pediatric Recipient Functional Outcome and Health-Related Quality of Life

Children with end-stage liver disease experience growth restriction, nutritional deficiencies, physical pain, debilitation, and cognitive issues related to chronic hepatic encephalopathy. As a result, functional recovery of pediatric recipients requires assessment of physical growth, cognitive and motor development, emotional maturity, and academic achievement. Evaluation of HRQOL in children remains a distinct challenge, because many are unable to report their experiences or changes in HRQOL in a meaningful way, especially if they were transplanted at a very young age. In many instances, assessment of HRQOL in pediatric recipients relies heavily on parental input and perspective, especially with regard to pretransplant condition.

Early studies in pediatric recipients emphasize that linear growth is augmented following LT, especially if exposure to corticosteroids is limited. Furthermore, about 60% of children experience catch-up growth in height and weight after LT. Anecdotal experience following transplantation of a 9 month-old, 4-kg twin with biliary atresia emphasizes this remarkable growth pattern: within 1 year the recipient, once one third the size of her healthy brother, equaled her sibling in height and weight. However, it should be remembered that most pediatric LT recipients do not achieve normal height when compared with their peers. Children of older age at LT, children with more restricted height at LT, those transplanted for fulminant hepatic failure or hepatoblastoma, and recipients with allograft complications and dysfunction were at greater risk for decreased growth after transplantation.

A more recent report from the Studies of Pediatric Liver Transplantation (SPLIT) research group details long-term outcomes after pediatric LT in 167 10-year survivors. At 10 years after LT, linear height was significantly below that expected in the normal population, and 69% of recipients were below the 50th percentile, and 23% below the 10th percentile. These results emphasize that although linear growth does increase after LT, many patients do not reach their expected, optimal height. Height restriction after pediatric LT was closely correlated with steroid therapy: patients under the 10th percentile in height were more than three times more likely to be receiving steroids than recipients above the 10th percentile. However, in this same group of 167 patients, there was no significant discrepancy in weight when compared to normal controls.

Cognitive development and academic progress are additional issues in the functional recovery of the pediatric LT recipient. In a single-institution study of 20-year survivors, the UCLA group reported that 90% of 20-year LT survivors completed high school, and 50% attended college. In studies with more limited follow-up, up to 77% of pediatric recipients have been shown to study at their appropriate grade level or 1 year behind, and about 10% require special classes for learning disabilities. A more recent study of 144 pediatric LT recipients, all 5 to 7 years of age and at least 2 years recovered from LT, reported that cognitive difficulties and learning disability are more prevalent in recipients than previously published. When tested with a variety of intelligence tests, the pediatric LT recipients performed statistically below test norms in terms of IQ and achievement measures. Mild to moderate IQ delays were found in 26% of patients, and severe delays in 4%. Twenty-five percent of LT recipients had reading or math scores below their IQ level, indicative of learning disabilities. Results from 10-year pediatric LT survivors indicate that 23% of patients had repeated a grade or been held back 1 year, about 10% had missed 20 school days in the preceding year, and 9% were diagnosed with attention-deficit/hyperactivity disorder. These results emphasize that although many pediatric LT recipients perform well in school, about one quarter will have significant obstacles to overcome and will require a coordinated, specialized approach to help these children reach their academic potential.

Additional challenges exist in the long-term care of pediatric LT recipients. In terms of HRQOL, 10-year pediatric LT survivors and their parents reported PedsQL 4.0 Generic Core Scale scores that were significantly lower than those of matched healthy children. The largest HRQOL effects for recipients were found in the Emotional Functioning and School Functioning Scales. Medical issues also were apparent in this cohort, because 47% of EBV seronegative recipients had converted to seropositive, and 5.3% had been diagnosed with posttransplantation lymphoproliferative disorder. Nine percent of 10-year survivors met glomerular filtration rate criteria for stage II chronic kidney disease, 20% had hypercholesterolemia, 26% had hypertriglyceridemia, and 9% were diagnosed with diabetes. A composite scoring system evaluating categories of allograft stability, absence of immunosuppression-induced comorbidities, and absence of need for additional medications revealed that only 32% of 10-year pediatric LT survivors met the ideal profile of stable initial allograft on monotherapy immunosuppression, normal growth, and absence of common comorbid conditions related to immunosuppression. Overall, compared to healthy peers, long-term survivors of pediatric LT have lower physical HRQOL, some physical disability, and less health care utilization. Some of these results stem from the ever-difficult transition from pediatric to adult transplant patient: some groups have facilitated this process with a specific “transition” coordinator, whereas others have used adolescent LT recipient “mentors” to support the recipient. The adolescent transition remains a critical period in the pediatric LT recipient's course and is associated with noncompliance, poor follow-up, and even graft dysfunction and loss. Although survival outcomes for pediatric LT have remained consistently excellent, much progress can be made through further refinements and protocols optimizing posttransplant care and development.