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This study investigated VWF release and cleavage and their association with PH and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Levels of VWF-Ag, VWF-N (VWF-propeptide), and VWF-A (VWF processed by the main VWF-cleaving protease ADAMTS13) were assessed in 229 patients with clinically stable ACLD (hepatic venous pressure gradient [HVPG]\u2009\u2265\u20096\u00a0mmHg; absence of bacterial infections or acute decompensation) undergoing HVPG-measurement. Liver-healthy individuals served as controls (n\u2009=\u200924).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>VWF-Ag and VWF-N were similarly accurate for the identification of clinically significant PH (CSPH; HVPG\u2009\u2265\u200910\u00a0mmHg) in compensated ACLD (AUROC: VWF-Ag 0.748; VWF-N 0.728). ADAMTS13 activity was similar between patients with ACLD and controls and did not correlate with PH and disease severity, whereas VWF cleavage decreased in patients with CSPH (i.e., VWF-Ag\/-A-ratio increased). In vitro VWF activity strongly reflected VWF-Ag levels (Spearman\u2019s r\u2009=\u20090.874, p\u2009&lt;\u20090.001), but decreased (vs. controls) in patients with CSPH when normalized to VWF-Ag levels (VWF-activity\/-Ag-ratio). VWF-Act\/-Ag ratio correlated negatively with ADAMTS13 activity (r\u2009=\u2013\u00a00.256, p\u2009&lt;\u20090.001). ADAMTS13 activity was independently predictive for (i) portal vein thrombosis (PVT) and (ii) hepatic decompensation or liver-related death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>VWF-Ag levels and its propeptide are similarly suitable surrogates of PH in patients with compensated ACLD. ADAMTS13-Act was not linked to disease and PH severity, however, when normalized to VWF-Ag, both VWF cleavage and VWF activity were decreased in patients with CSPH, as compared to liver-healthy individuals. Low ADAMTS13-Act was associated with presumably more procoagulant VWF and adverse outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>NCT03267615<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-023-10577-y","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T13:02:00Z","timestamp":1692622920000},"page":"1532-1544","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Von Willebrand factor processing in patients with advanced chronic liver disease and its relation to portal hypertension and clinical outcome"],"prefix":"10.1007","volume":"17","clinical-trial-number":[{"clinical-trial-number":"nct03267615","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8181-9146","authenticated-orcid":false,"given":"Benedikt","family":"Simbrunner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida Falk","family":"Villesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Scheiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Paternostro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Schwabl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert Friedrich","family":"St\u00e4ttermayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrig","family":"Marculescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Pinter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Quehenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Karsdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Lisman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Reiberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Julie","family":"Leeming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2330-0017","authenticated-orcid":false,"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,21]]},"reference":[{"key":"10577_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2021.01.003","author":"M Mandorfer","year":"2021","unstructured":"Mandorfer M, Simbrunner B. 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J Hepatol 2023;79(1):e27\u2013e28. https:\/\/doi.org\/10.1016\/j.jhep.2023.02.011","journal-title":"J Hepatol"}],"container-title":["Hepatology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-023-10577-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12072-023-10577-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-023-10577-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T00:38:16Z","timestamp":1700527096000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12072-023-10577-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,21]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["10577"],"URL":"https:\/\/doi.org\/10.1007\/s12072-023-10577-y","relation":{},"ISSN":["1936-0533","1936-0541"],"issn-type":[{"value":"1936-0533","type":"print"},{"value":"1936-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,21]]},"assertion":[{"value":"5 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 August 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"BeSi has received travel support from AbbVie and Gilead. IFV is a former full-time employee at Nordic Bioscience. BeSc received travel support from Abbvie and Gilead. DB has received travel support from AbbVie and Gilead, as well as speaker fees from AbbVie. PS received speaking honoraria from Bristol-Myers Squibb and Boehringer-Ingelheim, consulting fees from PharmaIN, and travel support from Falk and Phenex Pharmaceuticals. MP served as a speaker and\/or consultant and\/or advisory board member for AstraZeneca Bayer, Bristol-Myers Squibb, Ipsen, Eisai, Lilly, MSD, and Roche, and received travel support from Bayer, Bristol-Myers Squibb, and Roche. MT served as a speaker and\/or consultant and\/or advisory board member for Albireo, BiomX, Falk, Boehringer Ingelheim, Bristol-Myers SquibbGenfit, Gilead, Intercept, Janssen, MSD, Novartis, Phenex, Pliant, Regulus, and Shire and received travel support from AbbVie, Falk, Gilead, and Intercept as well as grants\/research support from Albireo, Alnylam, Cymabay, Falk, Gilead, Intercept, MSD, Takeda, and UltraGenyx. He is also co-inventor of patents on the medical use of 24-norursodeoxycholic acid. MK is a full-time employee at Nordic Bioscience and among the original inventors and patent holders of the Nordic Bioscience biomarkers. TR served as a speaker and\/or consultant and\/or advisory board member speaking honoraria from AbbVie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Roche, Siemens, and W. L. Gore & Associates and received travel support from AbbVie, Boehringer-Ingelheim, Gilead, and Roche as well as grants\/research support from AbbVie, Boehringer-Ingelheim, Gilead, Intercept, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, Siemens, and W. L. Gore & Associates. MM served as a speaker and\/or consultant and\/or advisory board member for AbbVie, Gilead, Collective Acumen, Takeda, and W. L. Gore & Associates and received travel support from AbbVie and Gilead. DJL is a full-time employee at Nordic Bioscience and among the original inventors and patent holders of the Nordic Bioscience biomarkers. TL, RP, RM, PQ and AFS declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}