{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T22:01:33Z","timestamp":1764540093651},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,7,21]],"date-time":"2013-07-21T00:00:00Z","timestamp":1374364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"SNF","award":["32323B_123815"],"award-info":[{"award-number":["32323B_123815"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Nodular regenerative hyperplasia (<jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content>) is a rare liver disease characterized by small regenerative nodules without fibrosis and can cause portal hypertension. Aetiology and pathogenesis of <jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content> remain unclear. We have recently shown that Notch1 knockout induces <jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content> with portal hypertension through vascular remodelling in mice. The aim of this study was to analyse histological and clinical data of <jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content> patients and to explore if the endothelial pathways identified in our <jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content> mouse model are also regulated in human <jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients were identified retrospectively from the pathology database. Clinical and laboratory patient data were retrieved. <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression was measured in liver biopsies from a subset of NRH patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Diagnosis of NRH was confirmed in needle biopsies of 51 patients, including 31 patients with grade 1, 12 patients with grade 2 and 8 patients with grade 3 NRH. Grade 3 nodularity significantly correlated with the presence of portal hypertension: 50% of the patients with grade 3 NRH vs. 6.5% with grade 1 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0105). <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression analysis in liver biopsies from 14 NRH patients and in primary human sinusoidal endothelial cells revealed downregulation of identical genes as in the murine NRH model, which are implicated in vascular differentiation: Notch1, delta\u2010like 4 (Dll4) and ephrinB2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this large <jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content> needle biopsy cohort, we demonstrated that advanced nodularity correlates with presence of portal hypertension. Downregulation of the endothelial signalling pathways Dll4\/Notch1 and ephrinB2\/EphB4 supports the hypothesis that human <jats:styled-content style=\"fixed-case\">NRH<\/jats:styled-content> is caused by a sinusoidal injury providing first insights into the molecular pathogenesis of this liver condition.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12261","type":"journal-article","created":{"date-parts":[[2013,6,24]],"date-time":"2013-06-24T02:05:02Z","timestamp":1372039502000},"page":"594-603","source":"Crossref","is-referenced-by-count":14,"title":["Downregulation of the Endothelial Genes Notch1 and EphrinB2 in Patients with Nodular Regenerative Hyperplasia"],"prefix":"10.1111","volume":"34","author":[{"given":"Sonja","family":"Rothweiler","sequence":"first","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Terracciano","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Tornillo","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Dill","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus H.","family":"Heim","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University Hospital Basel University Basel Basel 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