{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T12:04:04Z","timestamp":1785499444235,"version":"3.56.0"},"reference-count":14,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JPGN rep."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To elucidate the natural history of liver disease and identify the predictors of native liver survival (NLS) in a Brazilian cohort of children with Alagille syndrome (ALGS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Multicenter retrospective cohort study of children with ALGS. Descriptive statistics summarized clinical data. Overall survival was estimated using Kaplan\u2013Meier curves. NLS was analyzed with competing risk models. Associations between laboratory parameters and NLS were tested using Pearson\u2032s chi\u2010square.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 14 Brazilian reference centers, 120 children (52.5% male) were included, with mean age at diagnosis of 17.8 months and a median follow\u2010up time of 88.5 months. Most presented characteristic facies (89.9%), jaundice (88.2%), pruritus (87.9%), and neonatal cholestasis (79.2%). Thirty percent underwent liver transplantation (LT) and 6.7% died. Jaundice, xanthomas, hepatomegaly, splenomegaly, and presence of excoriations were significantly associated with the need for LT or death. Direct bilirubin (DB)\u2009&gt;\u20096\u2009mg\/dL, cholesterol &gt;300\u2009mg\/dL, increased aspartate aminotransferase (AST)\u2009&gt;\u20095 times the upper limit of normal (ULN), and AST\u2010to\u2010platelet ratio index (APRI)\u2009&gt;\u20091 were associated with a significantly increased risk of LT or death, with hazard ratios of 18.2 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, 95% confidence interval [95% CI]\u2009=\u20095.1\u201364.5), 3.4 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016, 95% CI\u2009=\u20091.3\u20139.2), 3.9 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018, 95% CI\u2009=\u20091.2\u201312.4), and 10.2 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013, 95% CI\u2009=\u20091.3\u201382.2), respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The main clinical manifestations included characteristic facies, jaundice, and pruritus. Higher rates of LT or death were associated with jaundice, xanthomas, hepatomegaly, splenomegaly and presence of excoriations. Higher rates of NLS were associated with DB levels below 6\u2009mg\/dL, cholesterol levels below 300\u2009mg\/dL, AST levels &lt;5x ULN, and an APRI\u2009&lt;\u20091.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jpr3.70224","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:42:27Z","timestamp":1785498147000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Brazilian Alagille syndrome study: New insights from a multicenter national cohort"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5079-5011","authenticated-orcid":false,"given":"Elisa","family":"Carvalho","sequence":"first","affiliation":[{"name":"Hospital da Crian\u00e7a de Bras\u00edlia Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Porta","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas Hospital Menino Jesus Brigadeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene Kazue","family":"Miura","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas Hospital Menino Jesus Brigadeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Helena Targa","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a Santo Antonio \u2010 UFCSPA Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana Rodrigues","family":"Silva","sequence":"additional","affiliation":[{"name":"Universidade Federal da Bahia Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha Silva","family":"Sandy","sequence":"additional","affiliation":[{"name":"Hospital Israelita Albert Einstein Jardim Leonor Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora Druve Tavares","family":"Fagundes","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais (UFMG) Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliene","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas Hospital Menino Jesus Brigadeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Falleiros","family":"Freitas","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas Hospital Menino Jesus Brigadeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Maria Alves","family":"de Tommaso","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas (Unicamp) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Sawamura","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina de Ribeir\u00e3o Preto da Universidade de S\u00e3o Paulo (USP) Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina Utz","family":"Melere","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a Santo Antonio \u2010 UFCSPA Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Maria Goncalves","family":"Vieira","sequence":"additional","affiliation":[{"name":"Hospital das Cl\u00ednicas de Porto Alegre Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Bel\u00e9m Pessoa de Melo","family":"Seixas","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a de Bras\u00edlia Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora de Carvalho","family":"Trevizoli","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a de Bras\u00edlia Bras\u00edlia Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre Rodrigues","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais (UFMG) Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Porta Miche","family":"Hirschfeld","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas Hospital Menino Jesus Brigadeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Pereira Sustovich","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas Hospital Menino Jesus Brigadeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cibele Dantas Ferreira","family":"Marques","sequence":"additional","affiliation":[{"name":"Universidade Federal da Bahia Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Angela Bellomo","family":"Brand\u00e3o","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas (Unicamp) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Borges","family":"Pinto","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a Concei\u00e7\u00e3o Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Helena Caldas","family":"Lopes","sequence":"additional","affiliation":[{"name":"Universidade Federal de S\u00e3o Paulo (UNIFESP) S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussara Melo de Cerqueira","family":"Maia","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio Onofre Lopes (UFRN) Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Vieira de","family":"Melo","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio Onofre Lopes (UFRN) Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Sores","family":"Silva","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a Santo Antonio \u2010 UFCSPA Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza Salgado","family":"Nader","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a Santo Antonio \u2010 UFCSPA Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Tereza","family":"Guiotti","sequence":"additional","affiliation":[{"name":"Universidade de S\u00e3o Paulo (USP) Ribeir\u00e3o Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Vacari","family":"Alc\u00e2ntara","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas (Unicamp) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Resende","sequence":"additional","affiliation":[{"name":"Hospital Universit\u00e1rio Maria Aparecida Pedrossian \u2013 UFMS Campo Grande Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Pereira Ribeiro","family":"Rocha","sequence":"additional","affiliation":[{"name":"Hospital Estadual da Crian\u00e7a do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilza Maria Medeiros","family":"Perin","sequence":"additional","affiliation":[{"name":"Hospital Infantil Joana de Gusm\u00e3o\u2010Florian\u00f3polis\u2010SC Florian\u00f3polis Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Teixeira","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais (UFMG) Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L\u00facia Baggio","family":"Danesi","sequence":"additional","affiliation":[{"name":"Hospital S\u00edrio Liban\u00eas Hospital Menino Jesus Brigadeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Hessel","sequence":"additional","affiliation":[{"name":"Universidade Estadual de Campinas (Unicamp) Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Themis Reverbel","family":"Silveira","sequence":"additional","affiliation":[{"name":"Hospital da Crian\u00e7a Santo Antonio \u2010 UFCSPA Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"12","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1136\/jmg.40.12.891","article-title":"Consequences of JAG1 mutations","volume":"40","author":"Kamath BM","year":"2003","journal-title":"J Med Genet"},{"issue":"11","key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"907","DOI":"10.3390\/diagnostics10110907","article-title":"Alagille syndrome: diagnostic challenges and advances in management","volume":"10","author":"Ayoub MD","year":"2020","journal-title":"Diagnostics"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.2147\/TACG.S86420","article-title":"Alagille syndrome: clinical perspectives","volume":"9","author":"Saleh M","year":"2016","journal-title":"Appl Clin Genet"},{"issue":"1","key":"e_1_2_7_5_1","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1086\/505332","article-title":"NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway","volume":"79","author":"McDaniell R","year":"2006","journal-title":"Am J Hum Genet"},{"issue":"3","key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/ejhg.2013.140","article-title":"Clinical utility gene card for: Alagille syndrome (ALGS)","volume":"22","author":"Leonard LD","year":"2014","journal-title":"Eur J Human Genet"},{"issue":"2","key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1136\/jmedgenet-2011-100544","article-title":"NOTCH2 mutations in Alagille syndrome","volume":"49","author":"Kamath BM","year":"2012","journal-title":"J Med Genet"},{"issue":"12","key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1002\/humu.23879","article-title":"Alagille syndrome mutation update: comprehensive overview of JAG1 and NOTCH2 mutation frequencies and insight into missense variant classification","volume":"40","author":"Gilbert MA","year":"2019","journal-title":"Hum Mutat"},{"issue":"1","key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/1098-1004(2001)17:1<18::AID-HUMU3>3.0.CO;2-T","article-title":"Jagged1 mutations in alagille syndrome","volume":"17","author":"Spinner NB","year":"2001","journal-title":"Hum Mutat"},{"issue":"10","key":"e_1_2_7_10_1","doi-asserted-by":"crossref","first-page":"608","DOI":"10.3390\/biom9100608","article-title":"The roles of notch signaling in liver development and disease","volume":"9","author":"Adams J","year":"2019","journal-title":"Biomolecules"},{"issue":"2","key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/hep.32761","article-title":"Natural history of liver disease in a large international cohort of children with Alagille syndrome: results from the GALA study","volume":"77","author":"Vandriel SM","year":"2023","journal-title":"Hepatology"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbi.2019.103208","article-title":"The REDCap consortium: building an international community of software platform partners","volume":"95","author":"Harris PA","year":"2019","journal-title":"J Biomed Inf"},{"issue":"3","key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/hep4.1468","article-title":"Outcomes of childhood cholestasis in Alagille syndrome: results of a multicenter observational study","volume":"4","author":"Kamath BM","year":"2020","journal-title":"Hepatol Commun"},{"issue":"10311","key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1016\/S0140-6736(21)01256-3","article-title":"Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study","volume":"398","author":"Gonzales E","year":"2021","journal-title":"Lancet"},{"issue":"7","key":"e_1_2_7_15_1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S2468-1253(24)00074-8","article-title":"Efficacy and safety of odevixibat in patients with Alagille syndrome (ASSERT): a phase 3, double\u2010blind, randomised, placebo\u2010controlled trial","volume":"9","author":"Ovchinsky N","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"}],"container-title":["JPGN Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jpr3.70224","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jpr3.70224","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jpr3.70224","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:42:29Z","timestamp":1785498149000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jpr3.70224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":14,"alternative-id":["10.1002\/jpr3.70224"],"URL":"https:\/\/doi.org\/10.1002\/jpr3.70224","archive":["Portico"],"relation":{},"ISSN":["2691-171X","2691-171X"],"issn-type":[{"value":"2691-171X","type":"print"},{"value":"2691-171X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"2025-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jpr3.70224"}}