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Author Notes:

Daniel H. Leung, MD, FAASLD, Associate Professor of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Gastroenterology, Hepatology, and Nutrition, Director of Hepatology and Liver Transplant Medicine, Medical Director, Viral Hepatitis Program; 6621 Fannin St, MWT 1010, Houston, TX 77030 (e-mail: dhleung@texaschildrens.org).

Heather Van Doren, Senior Medical Editor with Arbor Research Collaborative for Health, provided editorial assistance on this manuscript. The authors thank the children and their families whose participation made this study possible.

D.H.L. reports grant/research support from Abbvie, Gilead, and CF Foundation; he also serves on advisory panels for Merck and Gilead. B.M.K. is a consultant for Mirum, Albireo and Audentes; she has unrestricted educational grants from Mirum and Albireo. V.L.N. is a consultant for Albireo. P.R. reports grants from Gilead, Merck, BMS, AbbVie, Travere Therapeutics, Albireo, and Mirum, Arrowhead; and serving as a consultant for Gilead, Mirum, Albireo, Audentes, and Vertex. R.J.S. reports consulting for Albireo, Mirum/Shire, and Retrophin (all <$10,000 per year). K.M.L. reports consulting for Albireo, Mirum and Retrophin (now known as Travere Therapeutics). The remaining authors report no conflicts of interest. The study sponsors did not have a role in study design; collection, analysis, and interpretation of data; writing of the report; or the decision to submit the paper for publication. Dr Heubi passed away on August 4, 2021, prior to publication of this article.

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Research Funding:

This work was supported by funding from the Alpha-1 Foundation (University of Colorado Denver and Saint Louis University School of Medicine) and by U01 grants from the National Institute of Diabetes, Digestive and Kidney Diseases and UL1 grants from the National Center for Advancing Translational Sciences (NCATS): DK062445 [Mt. Sinai School of Medicine], DK062497 and UL1 TR000077 [Cincinnati Children's Hospital Medical Center, University of Cincinnati], DK103149 [Texas Children's Hospital], DK062470 [Children's Healthcare of Atlanta, Emory University], DK062481 and UL1 TR000003 [The Children's Hospital of Philadelphia, University of Pennsylvania], DK062456 [University of Michigan], DK084536 and UL1 TR000006 [Riley Hospital for Children, Indiana University], DK084575 and UL1 TR000423 [Seattle Children's Hospital, University of Washington], DK062500 and UL1 TR000004 [UCSF Children's Hospital, University of California San Francisco], DK062503 and UL1 TR000424 [Johns Hopkins School of Medicine], DK062466 and UL1 TR000005 [Children's Hospital of Pittsburgh, University of Pittsburgh], DK062453 and UL1 TR002535 [University of Colorado Denver, Children's Hospital Colorado], DK062452 and UL1 TR000448 [Washington University School of Medicine, St. Louis, St. Louis Children's Hospital], DK084538 and UL1 TR000130 [Children's Hospital Los Angeles, University of Southern California], DK062436 and UL1 TR000150 [Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University], DK103140 [University of Utah], DK103135 [Hospital for Sick Children (Toronto)].

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Gastroenterology & Hepatology
  • Nutrition & Dietetics
  • Pediatrics
  • Alagille syndrome
  • alpha-1 antitrypsin deficiency
  • intelligence quotient
  • neurocognitive
  • progressive familial intrahepatic cholestasis
  • SIMPLE NONINVASIVE INDEX
  • QUALITY-OF-LIFE
  • SIGNIFICANT FIBROSIS
  • WORKING-MEMORY
  • HEART
  • ADOLESCENTS
  • PREDICT

Neurodevelopmental Outcomes in Children With Inherited Liver Disease and Native Liver

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Journal Title:

JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION

Volume:

Volume 74, Number 1

Publisher:

, Pages 96-103

Type of Work:

Article | Final Publisher PDF

Abstract:

Objective: To evaluate neurodevelopmental status among children with inherited cholestatic liver diseases with native liver and variables predictive of impairment. Methods: Participants with Alagille syndrome (ALGS), progressive familial intrahepatic cholestasis (PFIC), and alpha 1 antitrypsin deficiency (A1AT) enrolled in a longitudinal, multicenter study and completed the Wechsler Preschool and Primary Scale of Intelligence-III or Intelligence Scale for Children-IV. Full Scale Intelligence Quotient (FSIQ) was analyzed continuously and categorically (>100, 85–99, 70–84, <70). Univariate linear regression was performed to study association between FSIQ and risk factors, stratified by disease. Results: Two hundred and fifteen completed testing (ALGS n = 70, PFIC n = 43, A1AT n = 102); median age was 7.6 years (3.0–16.9). Mean FSIQ in ALGS was lower than A1AT (94 vs 101, P = 0.01). Frequency of FSIQ < 85 (>1 standard deviation [SD] below average) was highest in ALGS (29%) versus 18.6% in PFIC and 12.8% in A1AT, and was greater than expected in ALGS based on normal distribution (29% vs 15.9%, P = 0.003). ALGS scored significantly lower than test norms in almost all Wechsler composites; A1AT scored lower on Working Memory and Processing Speed; PFIC was not different from test norms. Total bilirubin, alkaline phosphatase, albumin, hemoglobin, and parental education were significantly associated with FSIQ. Conclusions: Patients with ALGS are at increased risk of lower FSIQ, whereas our data suggest A1AT and PFIC are not. A1AT and ALGS appear vulnerable to working memory and processing speed deficits suggestive of attention/executive function impairment. Malnutrition, liver disease severity, and sociodemographic factors appear related to FSIQ deficits, potentially identifying targets for early interventions.

Copyright information:

© 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
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