Long-term neuropsychological outcomes after paediatric liver transplantation

Paediatric recipients of liver transplant present with a complicated clinical profile and can experience poorer long-term neuropsychological outcomes than their same-aged peers. However, there is a lack of evidence regarding their specific neuropsychological profile, and the extent to which any deficits relate to medical and transplant-related factors. Furthermore, this population is highly heterogenous. This thesis aimed to better understand the long-term neuropsychological outcomes of paediatric liver transplant recipients. It was hypothesised that the sample would demonstrate poorer outcomes compared to the normative population, but that this would differ according to primary diagnosis, medical and transplant-related factors. A sample of 41 children who had undergone transplantation for chronic liver disease completed neuropsychological testing and a series of self-, parent- and teacher report questionnaires on psychosocial functioning and quality of life. Eight children participated in an additional neuroimaging study to identify the presence of any brain pathology in a medically stable sample, as well as take measure of brain volumetrics to consider whether these were associated with medical and transplant-related factors an/or neuropsychological outcomes. Furthermore, a systematic review and meta-analysis was conducted across all studies reporting on intellectual and academic outcomes of children post-liver transplant (for either chronic disease, acute liver failure, metabolic diseases or a mix of the above). The sample demonstrated poorer neuropsychological outcomes compared to normative data across intellectual and academic outcomes, day-to-day functioning, and quality of life. Medical factors at time of transplant predicted long term neuropsychological outcomes. In particularly, longer time spent on waitlist predicted poorer long-term verbal intellect, working memory, reading ability and mathematical ability in children with biliary atresia. When a measure of disease severity was considered, the effect of waiting time was more pronounced in children with poorer liver function at transplantation. Two medically stable children demonstrated overt brain pathology on neuroimaging. Exploratory analysis of brain volumetrics showed an association with intellectual outcomes, and were predicted by body mass index at transplant. Results from the systematic review with meta-analysis reiterated the poorer long-term intellectual and academic functioning of children with liver transplant, and demonstrated the importance of separating analyses by primary diagnosis type. It also revealed variability in methodological approaches across the literature. To conclude, paediatric liver transplant recipients are a vulnerable population requiring ongoing support. The thesis identified clinical, research and policy areas requiring review in order to give these children the best start to life -- summary.