Baseline Analysis of a Young α-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension

Jeffrey H. Teckman*, Philip Rosenthal, Robert Abel, Lee M. Bass, Sonia Michail, Karen F. Murray, David A. Rudnick, Daniel W. Thomas, Cathie Spino, Ronen Arnon, Paula M. Hertel, James Heubi, Binita M. Kamath, Wikrom Karnsakul, Kathleen M. Loomes, John C. Magee, Jean P. Molleston, Rene Romero, Benjamin L. Shneider, Averell H. SherkerRonald J. Sokol

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Objectives: α-1-Antitrypsin (A1AT) deficiency is a common genetic disease with an unpredictable and highly variable course. The Childhood Liver Disease Research and Education Network is a National Institutes of Health, multicenter, longitudinal consortium studying pediatric liver diseases, with the objective of prospectively defining natural history and identifying disease modifiers. Methods: Longitudinal, cohort study of A1AT patients' birth through 25 years diagnosed as having liver disease, type PIZZ or PISZ. Medical history, physical examination, laboratory, imaging, and standardized survey tool data were collected during the provision of standard of care. Results: In the present report of the cohort at baseline, 269 subjects were enrolled between November 2008 and October 2012 (208 with their native livers and 61 postliver transplant). Subjects with mild disease (native livers and no portal hypertension [PHT]) compared to severe disease (with PHT or postliver transplant) were not different in age at presentation. A total of 57% of subjects with mild disease and 76% with severe disease were jaundiced at presentation (P = 0.0024). A total of 29% of subjects with native livers had PHT, but age at diagnosis and growth were not different between the no-PHT and PHT groups (P > 0.05). Subjects with native livers and PHT were more likely to have elevated bilirubin, ALT, AST, INR, and GGTP than the no-PHT group (P << 0.001), but overlap was large. Chemistries alone could not identify PHT. Conclusions: Many subjects with A1AT presenting with elevated liver tests and jaundice improve spontaneously. Subjects with PHT have few symptoms and normal growth. Longitudinal cohort follow-up will identify genetic and environmental disease modifiers.

Original languageEnglish (US)
Pages (from-to)94-101
Number of pages8
JournalJournal of pediatric gastroenterology and nutrition
Volume61
Issue number1
DOIs
StatePublished - Jul 23 2015

Keywords

  • cirrhosis
  • jaundice
  • liver enzymes
  • liver transplant
  • metabolic liver disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Gastroenterology

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    Teckman, J. H., Rosenthal, P., Abel, R., Bass, L. M., Michail, S., Murray, K. F., Rudnick, D. A., Thomas, D. W., Spino, C., Arnon, R., Hertel, P. M., Heubi, J., Kamath, B. M., Karnsakul, W., Loomes, K. M., Magee, J. C., Molleston, J. P., Romero, R., Shneider, B. L., ... Sokol, R. J. (2015). Baseline Analysis of a Young α-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension. Journal of pediatric gastroenterology and nutrition, 61(1), 94-101. https://doi.org/10.1097/MPG.0000000000000753