Shannon M. Vandriel
Li-Ting Li
Huiyu She
Jian-She Wang
Melissa A. Gilbert
Irena Jankowska
Piotr Czubkowski
Dorota Gliwicz-Miedzińska
Emmanuel M. Gonzales
Emmanuel Jacquemin
Jérôme Bouligand
Nancy B. Spinner
Kathleen M. Loomes
David A. Piccoli
Lorenzo D'Antiga
Emanuele Nicastro
Étienne Sokal
Tanguy Demaret
Noelle H. Ebel
Jeffrey A. Feinstein
Rima Fawaz
Silvia Nastasio
Florence Lacaille
Dominique Debray
Henrik Arnell
Björn Fischler
Susan Siew
Michael Stormon
Saul J. Karpen
Rene Romero
Kyung Mo Kim
Woo Yim Baek
Winita Hardikar
Sahana Shankar
Amin J. Roberts
Helen M. Evans
M Kyle Jensen
Marianne Kavan
Shikha S. Sundaram
Alexander Chaidez
Palaniswamy Karthikeyan
Maria Camila Sanchez
Maria Lorena Cavalieri
Henkjan J. Verkade
Way Seah Lee
James E. Squires
Christina Hajinicolaou
Chatmanee Lertudomphonwanit
Ryan T. Fischer, Children's Mercy HospitalFollow
Catherine Larson-Nath
Yael Mozer-Glassberg
Cigdem Arikan
Henry C. Lin
Jesus Quintero Bernabeu
Seema Alam
Deirdre A. Kelly
Elisa Carvalho
Cristina Targa Ferreira
Giuseppe Indolfi
Ruben E. Quiros-Tejeira
Pinar Bulut
Pier Luigi Calvo
Zerrin Önal
Pamela L. Valentino
Dev M. Desai
John Eshun
Maria Rogalidou
Antal Dezsőfi
Sabina Wiecek
Gabriella Nebbia
Raquel Borges Pinto
Victorien M. Wolters
María Legarda Tamara
Andréanne N. Zizzo
Jennifer Garcia
Kathleen Schwarz
Marisa Beretta
Thomas Damgaard Sandahl
Carolina Jimenez-Rivera
Nanda Kerkar
Jernej Brecelj
Quais Mujawar
Nathalie Rock
Cristina Molera Busoms
Wikrom Karnsakul
Eberhard Lurz
Ermelinda Santos-Silva
Niviann Blondet
Luis Bujanda
Uzma Shah
Richard J. Thompson
Bettina E E. Hansen
Binita M. Kamath
Global ALagille Alliance (GALA) Study Group

Document Type


Publication Date



DOI: 10.1002/hep.32761; PMCID: PMC9869940


Background and aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS.

Approach and results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18-year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver-related event (CEPH, transplant, or death). Children ( > 6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and <10.0 mg/dl had a 4.1-fold (95% confidence interval [CI], 1.6-10.8), and those ≥10.0 mg/dl had an 8.0-fold (95% CI, 3.4-18.4) increased risk of developing CEPH compared with those <5.0 mg/dl. Median TB levels between ≥5.0 and <10.0 mg/dl and >10.0 mg/dl were associated with a 4.8 (95% CI, 2.4-9.7) and 15.6 (95% CI, 8.7-28.2) increased risk of transplantation relative to < 5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver ( p < 0.001).

Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB < 5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of therapies.

Journal Title

Hepatology (Baltimore, Md.)





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Last Page


MeSH Keywords

Humans; Child; Male; Female; Alagille Syndrome; Retrospective Studies; Cholestasis; Hypertension, Portal


Alagille Syndrome; Retrospective Studies; Cholestasis; Portal Hypertension


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