{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:57:01Z","timestamp":1790773021920,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"LFB Laboratory"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>To identify prognostic factors for liver disease in children with alpha\u20101 antitrypsin deficiency, irrespective of phenotype, using the DEFI\u2010ALPHA cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective, then prospective from 2010, multicentre study including children known to have alpha\u20101 antitrypsin blood concentration below 0.8\u00a0g\/L, born in France since 1989. Clinical and biological data were collected. Liver disease was classified as \u201csevere\u201d (portal hypertension, liver failure, liver transplantation or death); \u201cmoderate\u201d (persistent abnormal liver biology without portal hypertension); and \u201cmild\/none\u201d (normal or almost normal liver biology and native liver). Prognostic factors for severe liver disease were evaluated using a Cox semiparametric model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In January 2017, 153 patients from 19 centres had been included; genotypes were PIZZ in 81.9%, PISZ in 8.1%, other in 10.0%. Mean\u00a0\u00b1\u00a0SD follow\u2010up was 4.7\u00a0\u00b1\u00a02.1\u00a0years. Half of patients had moderate liver disease. Twenty\u2010eight children (18.3%) had severe liver disease (mean age 2.5\u00a0years, range: 0\u201011.6): diagnosis of alpha\u20101 antitrypsin deficiency was made before two months of age in 65.4%, genotypes were PIZZ in 25 (89.3%), PISZ in 2, PIM<jats:sub>like<\/jats:sub>Z in 1, 15 children underwent liver transplantation, 1 child died at 3\u00a0years of age. Neonatal cholestasis was significantly associated with severe liver disease (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.007).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Alpha\u20101 antitrypsin\u2010deficient patients presenting with neonatal cholestasis were likely to develop severe liver disease. Some patients with non\u2010homozygous ZZ genotype can develop severe liver disease, such as PISZ and M variants, when associated with predisposing factors. Further genetic studies will help to identify other factors involved in the development of liver complications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14035","type":"journal-article","created":{"date-parts":[[2018,12,27]],"date-time":"2018-12-27T14:50:02Z","timestamp":1545922202000},"page":"1136-1146","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Liver disease related to alpha1\u2010antitrypsin deficiency in French children: The DEFI\u2010ALPHA cohort"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-790X","authenticated-orcid":false,"given":"Mathias","family":"Ruiz","sequence":"first","affiliation":[{"name":"H\u00e9patologie, Gastroent\u00e9rologie et Nutrition p\u00e9diatriques H\u00f4pital Femme M\u00e8re Enfant, Hospices Civils de Lyon Lyon France"},{"name":"Facult\u00e9 de M\u00e9decine Lyon\u2010Est Universit\u00e9 Claude Bernard Lyon 1 Lyon 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mol\u00e9culaire Grand\u2010Est H\u00f4pital Edouard Herriot, Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7824-5396","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Dumortier","sequence":"additional","affiliation":[{"name":"H\u00e9patologie H\u00f4pital Edouard Herriot, Hospices Civils de Lyon Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeleine","family":"Aumar","sequence":"additional","affiliation":[{"name":"Gastroent\u00e9rologie, H\u00e9patologie et Nutrition p\u00e9diatrique, Centre d'investigation clinique CHU Lille University of Lille Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Bridoux\u2010Henno","sequence":"additional","affiliation":[{"name":"Gastroent\u00e9rologie, H\u00e9patologie et Nutrition p\u00e9diatriques CHU Rennes Rennes 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