{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:35:38Z","timestamp":1771047338224,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,2]],"date-time":"2020-11-02T00:00:00Z","timestamp":1604275200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","award":["#10628"],"award-info":[{"award-number":["#10628"]}],"id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The effect of direct\u2010acting antiviral (DAA) therapy on extracellular matrix (ECM) turnover, a prominent feature of chronic hepatitis C (CHC), is unknown. ECM protein degradation and formation generate fragments reflecting the tissue turnover balance when quantified in the blood. PRO\u2010C3 and PRO\u2010C4 reflect type III and IV collagen formation; C3M and C4M are degradation markers of type III and IV. We aimed to assess the markers\u2019 dynamics with DAA therapy in CHC patients. Plasma PRO\u2010C3, PRO\u2010C4, C3M and C4M were assessed before, during and up till one year after 12\u201024\u00a0weeks of DAA therapy in 77 CHC patients with advanced fibrosis (n\u00a0=\u00a014) or cirrhosis (n\u00a0=\u00a063). Liver stiffness was evaluated using transient elastography. PRO\u2010C3, C3M and C4M levels decreased significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.00001) while PRO\u2010C4 was unchanged (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.20) during the study period. There was a steep decrease in the PRO\u2010C3\/C3M ratio during DAA therapy and follow\u2010up (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.02). The PRO\u2010C4\/C4M ratio was unchanged (<jats:italic>P<\/jats:italic>\u00a0&gt;\u00a0.27). The dynamics of the collagen markers behaved similarly between patients with advanced fibrosis and cirrhosis. However, the cirrhosis patients had &gt;20% higher levels of C3M, PRO\u2010C4 and C4M at all time points (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.05). The collagen markers correlated with liver stiffness at baseline and follow\u2010up.Markers of type III and IV collagen formation and degradation decreased during and after successful DAA therapy in CHC patients with advanced liver disease, and associated with disease severity. These results indicate an altered balance between collagen formation and degradation after viral clearance suggesting favourable effects on liver fibrosis.<\/jats:p>","DOI":"10.1111\/jvh.13416","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T15:32:51Z","timestamp":1602775971000},"page":"236-244","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Altered balance between collagen formation and degradation after successful direct\u2010acting antiviral therapy of chronic hepatitis C"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2494-0526","authenticated-orcid":false,"given":"Tea Lund","family":"Laursen","sequence":"first","affiliation":[{"name":"Department of Hepatology &amp; Gastroenterology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida Falk","family":"Villesen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana Julie","family":"Leeming","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten Asser","family":"Karsdal","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"S\u00f8lund","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Hvidovre Hospital Hvidovre Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Britta","family":"Tarp","sequence":"additional","affiliation":[{"name":"Diagnostic Centre Silkeborg Regional Hospital Silkeborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena Hagelskj\u00e6r","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Medicine Viborg Regional Hospital Viborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte Henneberg","family":"Holmboe","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Aalborg University Hospital Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Leutscher","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research North Denmark Regional Hospital &amp; Department of Clinical Medicine Aalborg University Aalborg Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex Lund","family":"Laursen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasja St\u00e6hr","family":"Gudmann","sequence":"additional","affiliation":[{"name":"Nordic Bioscience Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning","family":"Gr\u00f8nb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Hepatology &amp; Gastroenterology Aarhus University Hospital Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27826"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.05.010"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12578"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13758"},{"issue":"3","key":"e_1_2_6_6_1","first-page":"303","article-title":"The neo\u2010epitope specific PRO\u2010C3 ELISA measures true formation of type III collagen associated with liver and 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