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Longitudinal Outcomes in Young Patients with Alpha-1-Antitrypsin Deficiency with Native Liver Reveal that Neonatal Cholestasis is a Poor Predictor of Future Portal Hypertension

Authors :
Jeffrey Teckman
Philip Rosenthal
Kieran Hawthorne
Cathie Spino
Lee M. Bass
Karen F. Murray
Nanda Kerkar
John C. Magee
Saul Karpen
James E. Heubi
Jean P. Molleston
Robert H. Squires
Binita M. Kamath
Stephen L. Guthery
Kathleen M. Loomes
Averell H. Sherker
Ronald J. Sokol
Estella Alonso
Lee Bass
Susan Kelly
Mary Riordan
Hector Melin-Aldana
Jorge Bezerra
Kevin Bove
James Heubi
Alexander Miethke
Greg Tiao
Julie Denlinger
Erin Chapman
Ronald Sokol
Amy Feldman
Cara Mack
Michael Narkewicz
Frederick Suchy
Shikha Sundaram
Johan Van Hove
Benigno Garcia
Mikaela Kauma
Kendra Kocher
Matthew Steinbeiss
Mark Lovell
Kathleen Loomes
David Piccoli
Elizabeth Rand
Pierre Russo
Nancy Spinner
Jessi Erlichman
Samantha Stalford
Dina Pakstis
Sakya King
Robert Squires
Rakesh Sindhi
Veena Venkat
Kathy Bukauskas
Patrick McKiernan
Lori Haberstroh
James Squires
Laura Bull
Joanna Curry
Camille Langlois
Grace Kim
Jeffery Teckman
Vikki Kociela
Rosemary Nagy
Shraddha Patel
Jacqueline Cerkoski
Molly Bozic
Girish Subbarao
Ann Klipsch
Cindy Sawyers
Oscar Cummings
Simon Horslen
Karen Murray
Evelyn Hsu
Kara Cooper
Melissa Young
Laura Finn
Binita Kamath
Vicky Ng
Claudia Quammie
Juan Putra
Deepika Sharma
Aishwarya Parmar
Stephen Guthery
Kyle Jensen
Ann Rutherford
Amy Lowichik
Linda Book
Rebecka Meyers
Tyler Hall
Kasper Wang
Sonia Michail
Danny Thomas
Catherine Goodhue
Rohit Kohli
Larry Wang
Nisreen Soufi
Daniel Thomas
Nitika Gupta
Rene Romero
Miriam B. Vos
Rita Tory
John-Paul Berauer
Carlos Abramowsky
Jeanette McFall
Benjamin Shneider
Sanjiv Harpavat
Paula Hertel
Daniel Leung
Mary Tessier
Deborah Schady
Laurel Cavallo
Diego Olvera
Christina Banks
Cynthia Tsai
Richard Thompson
Edward Doo
Jay Hoofnagle
Averell Sherker
Rebecca Torrance
Sherry Hall
John Magee
Robert Merion
Wen Ye
Source :
J Pediatr
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

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.

Details

ISSN :
00223476
Volume :
227
Database :
OpenAIRE
Journal :
The Journal of Pediatrics
Accession number :
edsair.doi.dedup.....2cd1fb8e0c5fcfe9176513fd965cc3df
Full Text :
https://doi.org/10.1016/j.jpeds.2020.07.031