{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:27:52Z","timestamp":1788251272110,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013733","name":"Ipsen Biopharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020416","name":"Alagille Syndrome Alliance","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020416","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK134585"],"award-info":[{"award-number":["R01DK134585"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK140468"],"award-info":[{"award-number":["R01DK140468"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873543"],"award-info":[{"award-number":["81873543"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570468"],"award-info":[{"award-number":["81570468"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background & Aims<\/jats:title>\n \n Alagille syndrome (ALGS) is a rare, autosomal dominant disorder with high phenotypic heterogeneity. Disease\u2010causing variants are primarily identified in Jagged1 (\n JAG1<\/jats:italic>\n ), with fewer reported in\n NOTCH2<\/jats:italic>\n .\n JAG1<\/jats:italic>\n variants cause disease through a mechanism of haploinsufficiency, but the mechanism for\n NOTCH2<\/jats:italic>\n variants is not completely understood, making classification of variants more challenging. Using a large, international patient cohort acquired through the Global ALagille Alliance (GALA) study, we sought to improve classification of\n NOTCH2<\/jats:italic>\n variants and study phenotypic differences between\n NOTCH2\u2010<\/jats:italic>\n and\n JAG1\u2010<\/jats:italic>\n related disease.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Clinical and molecular data from 952 individuals with ALGS in GALA were analysed and disease features compared between those with\n JAG1<\/jats:italic>\n (\n n<\/jats:italic>\n \u2009=\u2009902) and\n NOTCH2<\/jats:italic>\n (\n n<\/jats:italic>\n \u2009=\u200934) variants. Previously reported and newly identified\n NOTCH2<\/jats:italic>\n variants were reinterpreted based on disease\u2010specific modifications to the American College of Medical Genetics and Genomics (ACMG) guidelines. The Kaplan\u2013Meier method was utilised to assess native liver survival (NLS) and overall survival (OS) and gene comparisons were made with the log\u2010rank test.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Thirty\n NOTCH2<\/jats:italic>\n variants, including 18 novel variants, were identified and classified in our GALA cohort. Phenotypic analyses revealed a significantly lower incidence of characteristic facies, posterior embryotoxon, cardiac involvement and butterfly vertebrae in individuals with\n NOTCH2<\/jats:italic>\n variants compared to those with\n JAG1<\/jats:italic>\n variants (\n p<\/jats:italic>\n \u2009<\u20090.001). No differences were identified in NLS or OS. Review of 61 previously reported\n NOTCH2<\/jats:italic>\n variants resulted in the re\u2010classification of 19 likely pathogenic or pathogenic to VOUS (31.1%) with less than half retaining their originally published classification (34.4%;\n n<\/jats:italic>\n \u2009=\u200921).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We report on a large global study on\n NOTCH2<\/jats:italic>\n genetics and phenotype, which increases the number of reported\n NOTCH2<\/jats:italic>\n variants by 30%. All variants were reclassified using current guidelines, and comparison of the\n JAG1<\/jats:italic>\n and\n NOTCH2<\/jats:italic>\n cohorts demonstrates clear phenotypic divergence between these groups. These data suggest that reliance on classical clinical phenotyping may miss patients with\n NOTCH2\u2010<\/jats:italic>\n related disease and supports an inclusive approach to genetic testing.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70251","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T13:14:52Z","timestamp":1753967692000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Phenotypic Divergence of\n JAG1<\/i>\n \u2010 and\n NOTCH2<\/i>\n \u2010Associated Alagille Syndrome & Disease\u2010Specific\n NOTCH2<\/i>\n Variant Classification Guidelines"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7157-2063","authenticated-orcid":false,"given":"Shannon M.","family":"Vandriel","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition The Hospital for Sick Children and the University of Toronto Toronto Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1165-4360","authenticated-orcid":false,"given":"Li\u2010Ting","family":"Li","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"She","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-586X","authenticated-orcid":false,"given":"Jian\u2010She","family":"Wang","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Loomes","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia The University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Piccoli","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia The University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irena","family":"Jankowska","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics The Children's Memorial Health Institute Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Czubkowski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics The Children's Memorial Health Institute Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Gliwicz\u2010Miedzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Nutrition Disturbances and Pediatrics The Children's Memorial Health Institute Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-3148","authenticated-orcid":false,"given":"Lorenzo","family":"D'Antiga","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation Ospedale Papa Giovanni XXIII Bergamo Italy"},{"name":"Department of Medicine and Surgery University of Milano \u2013 Bicocca Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Nicastro","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology, Gastroenterology and Transplantation Ospedale Papa Giovanni XXIII Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lacaille","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology\u2010Nutrition and Hepatology Units, Necker\u2010Enfants Malades Hospital University of Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Debray","sequence":"additional","affiliation":[{"name":"Pediatric Liver Unit, National Reference Centre for Rare Pediatric Liver Diseases (Biliary Atresia and Genetic Cholestasis), FILFOIE, ERN RARE LIVER, Necker\u2010Enfants Malades Hospital University of Paris Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9tienne M.","family":"Sokal","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie & H\u00e9patologie P\u00e9diatrique Cliniques Universitaires Saint\u2010Luc Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7605-9031","authenticated-orcid":false,"given":"Tanguy","family":"Demaret","sequence":"additional","affiliation":[{"name":"Service de Gastroent\u00e9rologie & H\u00e9patologie P\u00e9diatrique Cliniques Universitaires Saint\u2010Luc Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rima L.","family":"Fawaz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yale University School of Medicine New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Nastasio","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, & Nutrition Boston Children's Hospital and Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Mo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9672-8877","authenticated-orcid":false,"given":"Seak Hee","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Fischler","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital Karolinska University Hospital Stockholm Sweden"},{"name":"CLINTEC Karolinska Institutet, ERN Rare Liver Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Arnell","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology, Hepatology and Nutrition, Astrid Lindgren Children's Hospital Karolinska University Hospital Stockholm Sweden"},{"name":"Department of Women's and Children's Health Karolinska Institutet, ERN Rare Liver Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8797-2651","authenticated-orcid":false,"given":"Catherine","family":"Larson\u2010Nath","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology, and Nutrition University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winita","family":"Hardikar","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Clinical Nutrition Royal Children's Hospital Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahana","family":"Shankar","sequence":"additional","affiliation":[{"name":"Mazumdar Shaw Medical Center, Narayana Health Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shikha S.","family":"Sundaram","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children's Hospital of Colorado University of Colorado School of Medicine Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Chaidez","sequence":"additional","affiliation":[{"name":"Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children's Hospital of Colorado University of Colorado School of Medicine Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinar","family":"Bulut","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Hepatology Phoenix Children's Hospital Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pier Luigi","family":"Calvo","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital Azienda Ospedaliera\u2010Universitaria Citta' della Salute e della Scienza Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mureo","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Organ Transplantation Center National Center for Child Health and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niviann","family":"Blondet","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Seattle Children's Hospital Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eberhard","family":"Lurz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, LMU Munich, Dr. von Hauner Children's Hospital University Hospital Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Maria","family":"Kavallar","sequence":"additional","affiliation":[{"name":"Department of Paediatrics I Medical University of Innsbruck Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel M.","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Rare Pediatric Liver Diseases, FILFOIE, ERN RARE LIVER, Bic\u00eatre Hospital, AP\u2010HP University of Paris\u2010Saclay Le Kremlin\u2010Bic\u00eatre France"},{"name":"Inserm U1193, Hepatinov University of Paris\u2010Saclay Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7536-6272","authenticated-orcid":false,"given":"Emmanuel","family":"Jacquemin","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology and Liver Transplantation Unit, National Reference Centre for Rare Pediatric Liver Diseases, FILFOIE, ERN RARE LIVER, Bic\u00eatre Hospital, AP\u2010HP University of Paris\u2010Saclay Le Kremlin\u2010Bic\u00eatre France"},{"name":"Inserm U1193, Hepatinov University of Paris\u2010Saclay Orsay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Bouligand","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique Mol\u00e9culaire, Pharmacog\u00e9n\u00e9tique et Hormonologie, Assistance Publique\u2010H\u00f4pitaux de Paris, Centre Hospitalier Universitaire de Bic\u00eatre H\u00f4pitaux Universitaires Paris\u2010Saclay Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noelle H.","family":"Ebel","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Pediatrics Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Feinstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Cardiology), Lucile Packard Children's Hospital Stanford University School of Medicine Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Siew","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Children's Hospital at Westmead Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael O.","family":"Stormon","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology The Children's Hospital at Westmead Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul J.","family":"Karpen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology & Nutrition Children's Healthcare of Atlanta & Emory University School of Medicine Atlanta Georgia USA"},{"name":"Stravitz\u2010Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Romero","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology & Nutrition Children's Healthcare of Atlanta & Emory University School of Medicine Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Kyle","family":"Jensen","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Primary Children's Hospital University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Jaramillo","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Hepatology and Nutrition, Primary Children's Hospital University of Utah Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Squires","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Bedoyan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics University of Pittsburgh School of Medicine Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre A.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Liver Unit, Birmingham Women's & Children's Hospital NHS Trust University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Hartley","sequence":"additional","affiliation":[{"name":"Liver Unit, Birmingham Women's & Children's Hospital NHS Trust University of Birmingham Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henkjan J.","family":"Verkade","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Way Seah","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Faculty of Medicine University of Malaya Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chatmanee","family":"Lertudomphonwanit","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Pediatrics Ramathibodi Hospital Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan T.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Section of Hepatology, Department of Gastroenterology Children's Mercy Kansas City Kansas City Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry C.","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Department of Pediatrics Oregon Health and Science University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Rock","sequence":"additional","affiliation":[{"name":"Division of Pediatric Specialties, Department of Pediatrics, Gynecology, and Obstetrics, Swiss Pediatric Liver Center, University Hospitals Geneva University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Mozer\u2010Glassberg","sequence":"additional","affiliation":[{"name":"Schneider Children's Medical Center of Israel Institute of Gastroenterology, Nutrition and Liver Diseases Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amin J.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology Starship Child Health Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Paediatric Gastroenterology Starship Child Health Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wikrom","family":"Karnsakul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Nebbia","sequence":"additional","affiliation":[{"name":"Servizio di Epatologia Pediatrica Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victorien M.","family":"Wolters","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology University Medical Centre Utrecht Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L.","family":"Valentino","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Seattle Children's Hospital Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus Quintero","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"Pediatric Hepatology and Liver Transplant Department Hospital Universiatri Vall d'Hebron Barcelona Spain"},{"name":"European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER) Fondazione IRCCS San Gerardo dei Tintori Hospital Monza Italy"},{"name":"European Reference Network on Transplantation in Children (ERN\u2010TransplantChild), La Paz Institute of Biomedical Research Hospital Universitario La Paz Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal A.","family":"Aqul","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Centre in Dallas and Children's Health Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0794-2741","authenticated-orcid":false,"given":"Cigdem","family":"Arikan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Organ Transplant Koc University School of Medicine Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Legarda","family":"Tamara","sequence":"additional","affiliation":[{"name":"Paediatric Gastroenterology Unit Cruces University Hospital Bilbao Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Molera","family":"Busoms","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Hepatology and Nutrition Unit Hospital Sant Joan de D\u00e9u Esplugues de Llobregat Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Damgaard","family":"Sandahl","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3830-9823","authenticated-orcid":false,"given":"Giuseppe","family":"Indolfi","sequence":"additional","affiliation":[{"name":"Meyer Children's Hospital IRCCS Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6350-2057","authenticated-orcid":false,"given":"Andr\u00e9anne N.","family":"Zizzo","sequence":"additional","affiliation":[{"name":"Division of Paediatric Gastroenterology and Hepatology, London Health Sciences Centre, Children's Hospital Western University London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aglaia","family":"Zellos","sequence":"additional","affiliation":[{"name":"Mitera Children's Hospital Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben E.","family":"Quiros\u2010Tejeira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Nebraska and University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0987-341X","authenticated-orcid":false,"given":"Ermelinda","family":"Santos\u2010Silva","sequence":"additional","affiliation":[{"name":"Centro Materno\u2010Infantil do Norte Albino Aroso Centro Hospitalar Universit\u00e1rio de Santo Ant\u00f3nio Porto Portugal"},{"name":"UCIBIO \u2013 Applied Molecular Biosciences Unit, Biochemistry Laboratory, Department of Biological Sciences, Faculdade de Farm\u00e1cia Universidade do Porto Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen B.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Rady Children's Hospital San Diego University of California San Diego San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7871-8325","authenticated-orcid":false,"given":"Jernej","family":"Brecelj","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology, Hepatology and Nutrition University Medical Center Ljubljana Ljubljana Slovenia"},{"name":"Department of Pediatrics, Faculty of Medicine University Medical Center Ljubljana Ljubljana Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Camila","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Hepatology Division Hospital Italiano Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lorena","family":"Cavalieri","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Hepatology Division Hospital Italiano Buenos Aires Buenos Aires 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