{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:49:20Z","timestamp":1780584560031,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,25]],"date-time":"2020-11-25T00:00:00Z","timestamp":1606262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012774","name":"Innovationsfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012774","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>Direct\u2010acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance\u2010associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment\u2010failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral\u2010titre data were compared between the two patient groups, and HCV full\u2010length open reading frame deep\u2010sequencing was performed. The proportion of HCV NS5A\u2010RASs at baseline was higher in treatment\u2010failure (82%) than matched SVR patients (25%) (<jats:italic>p<\/jats:italic>\u00a0= .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment\u2010failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B\u2010substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3\u2010helicase and NS5A\u2010domain\u2010III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.<\/jats:p>","DOI":"10.1111\/jvh.13430","type":"journal-article","created":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T03:29:15Z","timestamp":1604201355000},"page":"302-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non\u2010target sites, for DAA\u2010based treatment and retreatment outcome"],"prefix":"10.1111","volume":"28","author":[{"given":"Ulrik","family":"Fahn\u00f8e","sequence":"first","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases Copenhagen University Hospital Hvidovre Denmark"},{"name":"Department of Immunology and Microbiology, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases Copenhagen University Hospital Hvidovre Denmark"},{"name":"Department of Immunology and Microbiology, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Microbiology Copenhagen University Hospital Hvidovre Denmark"},{"name":"Department of Science and Environment Roskilde University Roskilde Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"S\u00f8lund","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases Copenhagen University Hospital Hvidovre Denmark"},{"name":"Department of Infectious Diseases Copenhagen University Hospital Hvidovre 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Diseases Odense University Hospital Odense Denmark"},{"name":"Department of Clinical Research, Faculty of Health Sciences University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex L.","family":"Laursen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Aarhus University Hospital Skejby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Gerstoft","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Copenhagen University Hospital, Rigshospitalet Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Thielsen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Copenhagen University Hospital Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lone G.","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"},{"name":"Department of Medical Gastroenterology Zealand University Hospital K\u00f8ge Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders G.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Health Technology, Section for Bioinformatics Technical University of Denmark Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Sch\u00f8nning","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology Copenhagen University Hospital Hvidovre Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"},{"name":"Department of Clinical Microbiology Copenhagen University Hospital Rigshospitalet Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Weis","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Copenhagen University Hospital Hvidovre Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7815-4806","authenticated-orcid":false,"given":"Jens","family":"Bukh","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO\u2010HEP), Department of Infectious Diseases Copenhagen University Hospital Hvidovre Denmark"},{"name":"Department of Immunology and Microbiology, Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark"},{"name":"Department of Infectious Diseases Copenhagen University Hospital Hvidovre 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