Elevated Serum Bile Acids Predict Poor Liver Outcomes in Children With Alagille Syndrome: Results From the GALA Study Group

Carla Fiorella Murillo Perez; Shannon M Vandriel; Emmanuel M Gonzales; Jian-She Wang; Li-Ting Li; Huiyu She; Irena Jankowska; Piotr Czubkowski; Dorota Gliwicz-Miedzińska; Emmanuel Jacquemin; Jérôme Bouligand; Lorenzo D'Antiga; Emanuele Nicastro; Björn Fischler; Henrik Arnell; Susan M Siew; Michael Stormon; Kathleen M Loomes; David A Piccoli; Elizabeth B Rand; James E Squires; Saul J Karpen; Rene Romero; Mureo Kasahara; Zerrin Önal; Étienne Sokal; Tanguy Demaret; Sabina Wiecek; Florence Lacaille; Dominique Debray; Winita Hardikar; Sahana Shankar; Pamela L Valentino; Shikha S Sundaram; Noelle H Ebel; Jeffrey A Feinstein; Orith Waisbourd-Zinman; Henry C Lin; Nathalie Rock; Henkjan J Verkade; M Kyle Jensen; Catalina Jaramillo; Kyung Mo Kim; Seak Hee Oh; Jernej Brecemiclj; Seema Alam; Giuseppe Indolfi; Niviann Blondet; Rima Fawaz; Silvia Nastasio; Pier Luigi Calvo; Gabriella Nebbia; Cigdem Arikan; Catherine Larson-Nath; Andréanne N Zizzo; Thomas Damgaard Sandahl; Christos Tzivinikos; Nehal M El-Koofy; Mohamed A Elmonem; Amal A Aqul; Wikrom Karnsakul; Pinar Bulut; Nanda Kerkar; Victorien M Wolters; Amin J Roberts; Helen M Evans; Maria Camila Sanchez; Maria Lorena Cavalieri; Deirdre A Kelly; Jane Hartley; Way Seah Lee; Christina Hajinicolaou; Chatmanee Lertudomphonwanit; Ryan T Fischer; Jesus Quintero Bernabeu; Ruben E Quiros-Tejeira; Cristina Targa Ferreira; Elisa Carvalho; John Eshun; Aglaia Zellos; Antal Dezsőfi; Raquel Borges Pinto; Kathleen Schwarz; Maria Rogalidou; Jennifer Garcia; María Legarda Tamara; Marisa Beretta; Quais Mujawar; Ermelinda Santos-Silva; Cristina Molera Busoms; Eberhard Lurz; Cristina Gonçalves; Carolina Jimenez-Rivera; Jesus M Banales; Richard J Thompson; Bettina E Hansen; Binita M Kamath; Global ALagille Alliance (GALA) Study Group

doi:10.1111/liv.70423

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Elevated Serum Bile Acids Predict Poor Liver Outcomes in Children With Alagille Syndrome: Results From the GALA Study Group

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Elevated Serum Bile Acids Predict Poor Liver Outcomes in Children With Alagille Syndrome: Results From the GALA Study Group

Carla Fiorella Murillo Perez, Shannon M Vandriel, Emmanuel M Gonzales, Jian-She Wang, Li-Ting Li, Huiyu She, Irena Jankowska, Piotr Czubkowski, Dorota Gliwicz-Miedzińska, Emmanuel Jacquemin, …

Liver international, Vol.45(12), p.e70423

2025-12

DOI: https://doi.org/10.1111/liv.70423

PMID: 41250932

Appears in Miller School of Medicine - Latest Publications

Abstract

Alagille Syndrome - blood

Alagille Syndrome - complications

Alagille Syndrome - mortality

Bile Acids and Salts - blood

Bilirubin - blood

Child

Child, Preschool

Cholestasis - blood

Cholestasis - etiology

Female

Humans

Infant

Male

Prognosis

Proportional Hazards Models

Alagille syndrome (ALGS) is a rare disorder characterised by cholestasis and extrahepatic manifestations. Given the current era of ileal bile acid transporter (IBAT) inhibitor therapies that reduce serum bile acid (SBA) levels, we evaluated whether SBA predicts liver disease outcomes in ALGS. Patients were ascertained from the Global ALagille Alliance (GALA) cohort. A prognostic threshold of SBA 102 μmol/L was assessed as a time-dependent covariate in Cox regression analyses for native liver survival (NLS) and event-free survival (EFS), while adjusting for total bilirubin (TB) levels. 570 GALA patients were included (348 [61%] male). There was a moderate positive correlation between SBA and TB (Pearson correlation = 0.47, p < 0.001). SBA below 102 μmol/L was a significant predictor of outcomes (NLS: HR = 3.78, 95% CI 2.39-5.99, p < 0.001; EFS: HR = 3.44, 95% CI 2.35-5.04, p < 0.001). SBA remained a significant predictor for improved EFS after adjusting for TB clearance at 1 year (TB < 2 mg/dL; HR = 2.00, 95% CI 1.10-3.65, p = 0.02). Median SBA in the first year of life above 102 μmol/L, predicted lower NLS (67.2% vs. 83.5% at 7 years p = 0.05) and EFS (63.4% vs. 80.9% at 7 years, p = 0.02). Lower SBA in children with ALGS liver disease predicts improved NLS and EFS. SBA is also associated with NLS in children with ALGS who clear their bilirubin, that is, those with anicteric cholestasis. Although the patients studied here did not receive IBAT inhibition, these data suggest that lowering SBA may improve important clinical outcomes.

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Title: Elevated Serum Bile Acids Predict Poor Liver Outcomes in Children With Alagille Syndrome: Results From the GALA Study Group
Creators: Carla Fiorella Murillo Perez - University of Toronto
Shannon M Vandriel - University of Toronto
Emmanuel M Gonzales - Bicêtre Hospital
Jian-She Wang - Children's Hospital of Fudan University
Li-Ting Li - Children's Hospital of Fudan University
Huiyu She - Children's Hospital of Fudan University
Irena Jankowska - Children's Memorial Health Institute
Piotr Czubkowski - Children's Memorial Health Institute
Dorota Gliwicz-Miedzińska - Children's Memorial Health Institute
Emmanuel Jacquemin - Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics, The Children's Memorial Health Institute, Warsaw, Poland
Jérôme Bouligand - Bicêtre Hospital
Lorenzo D'Antiga - Department of Medicine and Surgery, University of Milano, Milan, Italy
Emanuele Nicastro - Ospedale Papa Giovanni XXIII
Björn Fischler - Karolinska University Hospital
Henrik Arnell - Karolinska University Hospital
Susan M Siew - Children's Hospital at Westmead
Michael Stormon - Children's Hospital at Westmead
Kathleen M Loomes - Children's Hospital of Philadelphia
David A Piccoli - Children's Hospital of Philadelphia
Elizabeth B Rand - Children's Hospital of Philadelphia
James E Squires - University of Pittsburgh
Saul J Karpen - Virginia Commonwealth University
Rene Romero - Children's Healthcare of Atlanta
Mureo Kasahara - National Center For Child Health and Development
Zerrin Önal - Istanbul University
Étienne Sokal - Cliniques Universitaires Saint-Luc
Tanguy Demaret - Cliniques Universitaires Saint-Luc
Sabina Wiecek - Medical University of Silesia
Florence Lacaille - Pediatric Gastroenterology-Nutrition and Hepatology Units, Necker-Enfants Malades Hospital, University of Paris, Paris, France
Dominique Debray - Hôpital Necker-Enfants Malades
Winita Hardikar - Royal Children's Hospital
Sahana Shankar - Narayana Health
Pamela L Valentino - Seattle Children's Hospital
Shikha S Sundaram - University of Colorado Denver
Noelle H Ebel - Stanford University
Jeffrey A Feinstein - Lucile Packard Children's Hospital
Orith Waisbourd-Zinman - Schneider Children's Medical Center
Henry C Lin - University of Portland
Nathalie Rock - University of Geneva
Henkjan J Verkade - University Medical Center Groningen
M Kyle Jensen - Primary Children's Hospital
Catalina Jaramillo - Primary Children's Hospital
Kyung Mo Kim - University of Ulsan
Seak Hee Oh - Asan Medical Center
Jernej Brecemiclj - Ljubljana University Medical Centre
Seema Alam - Institute of Liver and Biliary Sciences
Giuseppe Indolfi - Meyer Children's Hospital
Niviann Blondet - Seattle Children's Hospital
Rima Fawaz - Yale University
Silvia Nastasio - Boston Children's Hospital
Pier Luigi Calvo - Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Citta' della Salute e della Scienza, Turin, Italy
Gabriella Nebbia - Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Cigdem Arikan - Koç University
Catherine Larson-Nath - University of Minnesota
Andréanne N Zizzo - Western University
Thomas Damgaard Sandahl - Aarhus University Hospital
Christos Tzivinikos - Mohammed Bin Rashid University of Medicine and Health Sciences
Nehal M El-Koofy - Cairo University
Mohamed A Elmonem - Cairo University
Amal A Aqul - The University of Texas Southwestern Medical Center
Wikrom Karnsakul - Johns Hopkins University School of Medicine
Pinar Bulut - Phoenix Children's Hospital
Nanda Kerkar - University of Rochester Medical Center
Victorien M Wolters - University Medical Center Utrecht
Amin J Roberts - Starship Children's Health
Helen M Evans - Starship Children's Health
Maria Camila Sanchez - Hospital Italiano de Buenos Aires
Maria Lorena Cavalieri - Hospital Italiano de Buenos Aires
Deirdre A Kelly - Birmingham Women’s and Children’s NHS Foundation Trust
Jane Hartley - Birmingham Women’s and Children’s NHS Foundation Trust
Way Seah Lee - University of Malaya
Christina Hajinicolaou - Chris Hani Baragwanath Hospital
Chatmanee Lertudomphonwanit - Ramathibodi Hospital
Ryan T Fischer - Children's Mercy Hospital
Jesus Quintero Bernabeu - Biogipuzkoa Health Research Institute
Ruben E Quiros-Tejeira - Children's Hospital & Medical Center
Cristina Targa Ferreira - Universidade Federal de Ciências da Saúde de Porto Alegre
Elisa Carvalho - Hospital Universitário de Brasília
John Eshun - Le Bonheur Children's Hospital
Aglaia Zellos - Mitera Children's Hospital, Athens, Greece
Antal Dezsőfi - Semmelweis University
Raquel Borges Pinto - Grupo Hospitalar Conceição
Kathleen Schwarz - University of California San Diego
Maria Rogalidou - National and Kapodistrian University of Athens
Jennifer Garcia - Miami Transplant Institute
María Legarda Tamara - Hospital de Cruces
Marisa Beretta - Wits University Donald Gordon Medical Centre
Quais Mujawar - University of Manitoba
Ermelinda Santos-Silva - Universidade do Porto
Cristina Molera Busoms - Hospital Sant Joan de Déu Barcelona
Eberhard Lurz - Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU Munich, Munich, Germany
Cristina Gonçalves - Pediatric Gastroenterology/Hepatology Center Lisbon, Lisbon, Portugal
Carolina Jimenez-Rivera - Children's Hospital of Eastern Ontario
Jesus M Banales - Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Richard J Thompson - King's College London
Bettina E Hansen - Toronto General Hospital
Binita M Kamath - Hospital for Sick Children
Global ALagille Alliance (GALA) Study Group
Publication Details: Liver international, Vol.45(12), p.e70423
Publisher: WILEY; HOBOKEN
Number of pages: 11
Grant note: Ipsen Biopharmaceuticals Alagille Syndrome Alliance 81873543 / National Natural Science Foundation of China 81570468 / National Natural Science Foundation of China Mirum Pharmaceuticals Inc.
Academic Unit: UMMG Dept of Pediatrics - Gastroenterology; Miller School of Medicine; UMMG Department of Pediatrics
Language: English
Resource Type: Journal article
PMID: 41250932
Record Identifier: 991032860511302976