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Impact of Immunosuppression on Executive Functioning After Pediatric Liver Transplantation

An Observational Cohort Study

Goldschmidt, Imeke*; van Dick, Rolf; Jacobi, Christoph; Junge, Norman*; Pfister, Eva*; Richter, Nico§; Baumann, Ulrich*

Journal of Pediatric Gastroenterology and Nutrition: April 2019 - Volume 68 - Issue 4 - p 480–487
doi: 10.1097/MPG.0000000000002274
Original Articles: Hepatology

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.

*Department of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Hannover

Institute of Social Psychology, Goethe University Frankfurt, Frankfurt

Department of Paediatric Pneumology and Neonatology

§Department of Abdominal and Transplant Surgery, Hannover Medical School, Hannover, Germany.

Address correspondence and reprint requests to Imeke Goldschmidt, MD, Department of Paediatric Gastroenterology and Hepatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany (e-mail:

Received 12 June, 2018

Accepted 22 December, 2018

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (

The original PedsQL module on cognitive functioning was provided by MAPI research trust for a structured translation. No funds were received for the translation. MAPI research trust did not participate in or influence data analysis or interpretation.

This study was supported by an unrestricted grant by Astellas Pharma. Since an analysis of effect of immunosuppression on cognitive functioning is included in the study, this may be perceived as a conflict of interest. Astellas Pharma did not participate in or influence data analysis or interpretation.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,