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Long-Term Effects of Cholestatic Liver Disease in Childhood on Neuropsychological Outcomes and Neurochemistry

Talcott, Joel B.*; Beath, Sue V.; Patel, Tulpesh*; Griffiths, Gareth; Kelly, Deirdre A.

Journal of Pediatric Gastroenterology and Nutrition: May 6, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/MPG.0000000000002380
Original Article: PDF Only

OBJECTIVES: Children with liver disease have increased risk of long-term cognitive deficits. We differentiated between the effects of chronic liver disease from that associated with transplantation by recruiting children with cholestatic liver disease with and without transplantation.

METHODS: Psychometric measures and magnetic resonance spectroscopy were obtained for 3 groups of children: stable liver disease (SLD) without transplantation; cholestatic liver disease (CLD) from birth with transplantation; and individuals healthy to 18 months of age, prior to transplantation for acute liver failure (ALF).

RESULTS: Cognitive outcomes between children with different disease histories were significantly associated with the duration of liver disease but not the effects of transplantation, including that of immune suppression. Lower intellectual ability was most frequently observed in the CLD group, whereas all of the ALF group scored within the normal range. Myo-inositol and glutamate/glutamine concentrations in cortex were significantly associated with disease duration across the cohort. Neuro-metabolite profiles in SLD were consistent with subclinical encephalopathy. Impaired growth in early childhood was associated with later cognitive performance.

CONCLUSION: Children with prolonged liver disease had the poorest cognitive outcomes despite successful transplantation, suggesting that prolonged cholestasis before transplantation adversely impacts neurodevelopment, and reinforces the need for timely interventions.

*Aston Brain Centre, School of Life and Health Sciences, Aston University, Birmingham, UK

The Liver Unit, Birmingham Women's & Children's Hospital, Birmingham, UK

Chemical Engineering and Applied Chemistry, School of Engineering and Applied Sciences, Aston University, Birmingham, UK.

Address correspondence and reprint requests to Joel B. Talcott, PhD, Aston Brain Centre, Aston University, Birmingham UK (e-mail:

Received 16 October, 2018

Accepted 18 April, 2019

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 (

Conflicts of Interest and Source of Funding: None of the authors have any conflict of interest to disclose. This research was financially supported by an EPSRC CASE award to J Talcott and G Griffiths and by The Children's Liver Fund and The Dr. Hadwen Trust.

Disclosures: JT: Participated in research design, collection of primary data, data analysis and manuscript preparation. SB: Participated in research design, submitted proposal for ethical approval; collection of primary data, data analysis and manuscript preparation. GG: Participated in research design and manuscript preparation. TP: Participated in research design, collected primary data and carried out data analysis and manuscript preparation. DK: Participated in research design, data analysis and manuscript preparation

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