{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T06:30:38Z","timestamp":1759991438260},"reference-count":56,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T00:00:00Z","timestamp":1447718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Hepato Biliary Pancreat"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biliary atresia (BA) includes a sclerosing cholangiopathy whose nature is not fully deciphered. Aiming to evaluate the role of an arteriopathy as an etiologic factor in BA, we investigated hypoxia and the correlated angiogenic response in livers from affected patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene expression of the molecular axis: hypoxia\u2010inducible factor (<jats:italic>HIF<\/jats:italic>)<jats:italic>1a<\/jats:italic>, <jats:italic>HIF2a<\/jats:italic> and vascular endothelial growth factor A (<jats:italic>VEGFA<\/jats:italic>)\/<jats:italic>VEGFR1<\/jats:italic>, <jats:italic>VEGFR2<\/jats:italic>. Liver biopsy specimens collected at exploratory laparotomy of age\u2010matched patients with isolated, cytomegalovirus IgM\u2010negative BA (<jats:italic>n\u00a0=<\/jats:italic>\u00a032) and intrahepatic cholestasis (IHC, <jats:italic>n\u00a0=<\/jats:italic>\u00a09) were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed higher <jats:italic>HIF1a<\/jats:italic> and <jats:italic>HIF2a<\/jats:italic> expression in BA than in IHC. Paradoxically, <jats:italic>VEGFR2<\/jats:italic>, the main target of VEGFA\u2010induced angiogenesis, was underexpressed in BA, and <jats:italic>VEGFA<\/jats:italic> was decreased in most BA patients. Patients with the highest expression of <jats:italic>HIF<\/jats:italic>s and the lowest <jats:italic>VEGFA<\/jats:italic> and <jats:italic>VEGFR2<\/jats:italic> were essentially the same, indicating hypoxia without the necessary angiogenesis. This group included most BA patients and, except for <jats:italic>HIF2a<\/jats:italic>, they were older and presented increased bilirubin serum levels. In the highest <jats:italic>HIF2a<\/jats:italic>\/lowest <jats:italic>VEGFR2<\/jats:italic> subsets, gene expression of the cytokeratin 19, marker of cholangiocyte phenotype, was decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study suggests that hypoxia\u2010ischemia is present in the livers of patients with BA, progresses over time and leads to a decreased cholangiocyte mass.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jhbp.297","type":"journal-article","created":{"date-parts":[[2015,10,29]],"date-time":"2015-10-29T02:57:35Z","timestamp":1446087455000},"page":"846-854","source":"Crossref","is-referenced-by-count":15,"title":["Hypoxic\u2010ischemic gene expression profile in the isolated variant of biliary atresia"],"prefix":"10.1002","volume":"22","author":[{"given":"Leila Xavier Sinigaglia","family":"Fratta","sequence":"first","affiliation":[{"name":"Experimental Laboratory of Hepatology and Gastroenterology Hospital de Cl\u00ednicas de Porto 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