Jeffrey Teckman1, Philip Rosenthal2, Kieran Hawthorne3, Cathie Spino4, Lee M Bass5, Karen F Murray6, Nanda Kerkar7, John C Magee8, Saul Karpen9, James E Heubi10, Jean P Molleston11, Robert H Squires12, Binita M Kamath13, Stephen L Guthery14, Kathleen M Loomes15, Averell H Sherker16, Ronald J Sokol17. 1. Pediatrics and Biochemistry, Saint Louis University, Cardinal Glennon Children's Medical Center, Saint Louis, MO. 2. Pediatrics and Surgery, University of California San Francisco, San Francisco, CA. 3. Arbor Research Collaborative for Health, Ann Arbor, MI. 4. Biostatistics, University of Michigan, Ann Arbor, MI. 5. Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL. 6. Pediatric Gastroenterology and Hepatology, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA. 7. Pediatric Gastroenterology, Children's Hospital Los Angeles, Los Angeles, CA. 8. Surgery, University of Michigan School of Medicine, Ann Arbor, MI. 9. Pediatrics, Emory University, Children's Healthcare Atlanta, Atlanta, GA. 10. Pediatric Gastroenterology and Hepatology, Children's Hospital Medical Center, Cincinnati, OH. 11. Pediatric Gastroenterology, Hepatology and Nutrition, James Whitcomb Riley Hospital for Children, Indianapolis, IN. 12. Pediatrics, University of Pittsburgh, Pittsburgh, PA. 13. Pediatric Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada. 14. Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Utah, and Intermountain Primary Children's Hospital, Salt Lake City, UT. 15. Pediatric Gastroenterology, Children's Hospital of Philadelphia, Philadelphia, PA. 16. National Institute of Diabetes, Digestive and Kidney Disease, National Institutes of Health, Baltimore, MD. 17. Pediatric Gastroenterology, Hepatology and Nutrition, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
Abstract
OBJECTIVES: To identify predictors of portal hypertension, liver transplantation, and death in North American youth with alpha-1-antitrypsin (AAT) deficiency, and compare with patients with AAT deficiency elsewhere. STUDY DESIGN: The Childhood Liver Disease Research Network Longitudinal Observational Study of Genetic Causes of Intrahepatic Cholestasis is a prospective, cohort study of pediatric cholestatic liver diseases, including AAT deficiency, enrolling PIZZ and PISZ subjects 0-25 years of age seen since November 2007 at 17 tertiary care centers in the US and Canada. Data from standard-of-care baseline and annual follow-up visits were recorded from medical records, history, physical examination, and laboratory studies. Participants with portal hypertension were identified based on data collected. RESULTS: We enrolled 350 participants (60% male) with a native liver; 278 (79%) entered the cohort without portal hypertension and 18 developed portal hypertension during follow-up. Thirty participants required liver transplantation; 2 patients died during 1077 person-years of follow-up. There was no difference in participants with or without preceding neonatal cholestasis progressing to transplantation or death during the study (12% vs 7%; P = .09), or in experiencing portal hypertension (28% vs 21%; P = .16); the hazard ratio for neonatal cholestasis leading to portal hypertension was P = .04. Development of portal hypertension was associated with a reduced height Z-score. CONCLUSIONS: Portal hypertension in youth with AAT deficiency impacts growth measures. Progression to liver transplantation is slow and death is rare, but the risk of complications and severe liver disease progression persists throughout childhood. A history of neonatal cholestasis is a weak predictor of severe disease.
OBJECTIVES: To identify predictors of portal hypertension, liver transplantation, and death in North American youth with alpha-1-antitrypsin (AAT) deficiency, and compare with patients with AAT deficiency elsewhere. STUDY DESIGN: The Childhood Liver Disease Research Network Longitudinal Observational Study of Genetic Causes of Intrahepatic Cholestasis is a prospective, cohort study of pediatric cholestatic liver diseases, including AAT deficiency, enrolling PIZZ and PISZ subjects 0-25 years of age seen since November 2007 at 17 tertiary care centers in the US and Canada. Data from standard-of-care baseline and annual follow-up visits were recorded from medical records, history, physical examination, and laboratory studies. Participants with portal hypertension were identified based on data collected. RESULTS: We enrolled 350 participants (60% male) with a native liver; 278 (79%) entered the cohort without portal hypertension and 18 developed portal hypertension during follow-up. Thirty participants required liver transplantation; 2 patients died during 1077 person-years of follow-up. There was no difference in participants with or without preceding neonatal cholestasis progressing to transplantation or death during the study (12% vs 7%; P = .09), or in experiencing portal hypertension (28% vs 21%; P = .16); the hazard ratio for neonatal cholestasis leading to portal hypertension was P = .04. Development of portal hypertension was associated with a reduced height Z-score. CONCLUSIONS: Portal hypertension in youth with AAT deficiency impacts growth measures. Progression to liver transplantation is slow and death is rare, but the risk of complications and severe liver disease progression persists throughout childhood. A history of neonatal cholestasis is a weak predictor of severe disease.
Authors: Ludmila Pawlikowska; Sandra Strautnieks; Irena Jankowska; Piotr Czubkowski; Karan Emerick; Anthony Antoniou; Catherine Wanty; Bjorn Fischler; Emmanuel Jacquemin; Sami Wali; Samra Blanchard; Inge-Merete Nielsen; Billy Bourke; Shirley McQuaid; Florence Lacaille; Jane A Byrne; Albertien M van Eerde; Kaija-Leena Kolho; Leo Klomp; Roderick Houwen; Peter Bacchetti; Steven Lobritto; Vera Hupertz; Patricia McClean; Giorgina Mieli-Vergani; Benjamin Shneider; Antal Nemeth; Etienne Sokal; Nelson B Freimer; A S Knisely; Philip Rosenthal; Peter F Whitington; Joanna Pawlowska; Richard J Thompson; Laura N Bull Journal: J Hepatol Date: 2010-04-13 Impact factor: 25.083
Authors: Shujuan Pan; Lu Huang; John McPherson; Donna Muzny; Farshid Rouhani; Mark Brantly; Richard Gibbs; Richard N Sifers Journal: Hepatology Date: 2009-07 Impact factor: 17.425