Impact of Immunosuppression On Executive Functioning After Pediatric Liver Transplantation: An Observational Cohort Study

OBJECTIVES: Children after liver transplantation show increased rates of impaired cognitive functioning. We aimed to assess the potential effects of immunosuppressive therapy on executive functioning measured by the Children's Color Trail Test and the cognitive functioning module of the PedsQL (cogPedsQL) in liver transplanted children to explore potential targets for intervention to improve executive functioning. METHODS: We performed a cross-sectional study in 155 children (78 girls) aged 10.4 (2-18) years at 5.0 (0.1-17) years after liver transplantation, with follow-up at 6 months in n = 114. Executive functioning was assessed by Children's Color Trail Test (ages 8-16) and by patients and parent-proxy cogPedsQL (ages 5-18/2-18, respectively). Results were correlated with clinical parameters. Stability of results over time was compared between n = 23 patients who for clinical reasons switched from twice daily calcineurin inhibitor (CNI) to once-daily slow-release tacrolimus (Tac) during the study period, and patients with unchanged CNI. RESULTS: Worse executive functioning was associated with longer stay in the intensive care unit and longer time elapsed since transplantation. No difference was found between users of cyclosporine and Tac. Children on once-daily slow-release Tac performed better than children on twice-daily Tac. In children who switched from twice-daily CNI to once-daily Tac, parent-proxy cogPedsQL improved significantly compared to stable results in the nonswitch group. CONCLUSIONS: In addition to a strong impact of disease burden around transplantation, executive functioning appears to deteriorate over time. Although there is no clear-cut advantage of any CNI, once-daily Tac appears to be advantageous compared to twice-daily Tac.