{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:52:38Z","timestamp":1780919558503,"version":"3.54.1"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Data on the prevalence of resistance\u2010associated substitutions (RASs) and their implications for treatment with direct\u2010acting antivirals (DAAs) are sparse in European patients with HCV genotype 4. This study investigated RASs before and after DAA failure in different genotype 4 subtypes and evaluated retreatment efficacies. Samples of 195 genotype 4\u2010infected patients were collected in the European Resistance Database and investigated for NS3, NS5A and NS5B RASs. Retreatment efficacies in DAA failure patients were analysed retrospectively. After NS5A inhibitor (NS5Ai) failure, subtype 4r was frequent (30%) compared to DAA\u2010na\u00efve patients (5%) and the number of NS5A RASs was significantly higher in subtype 4r compared to 4a or 4d (median three RASs vs no or one RAS, respectively, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a0.0001). RASsL28V, L30R and M31L pre\u2010existed in subtype 4r and were maintained after NS5Ai failure. Typical subtype 4r RASs were located in subdomain 1a of NS5A, close to membrane interaction and protein\u2010protein interaction sites that are responsible for multimerization and hence viral replication. Retreatment of 37 DAA failure patients was highly effective with 100% SVR in prior SOF\/RBV, PI\/SOF and PI\/NS5Ai failures. Secondary virologic failures were rare (n\u00a0=\u00a02; subtype 4d and 4r) and only observed in prior NS5Ai\/SOF failures (SVR 90%). In conclusion, subtype 4r harboured considerably more RASs compared to other subtypes. A resistance\u2010tailored retreatment using first\u2010 and second\u2010generation DAAs was highly effective with SVR rates \u226590% across all subtypes and first\u2010line treatment regimens.<\/jats:p>","DOI":"10.1111\/jvh.13322","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T21:23:50Z","timestamp":1589318630000},"page":"974-986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Resistance\u2010associated substitutions in patients with chronic hepatitis C virus genotype 4 infection"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6990-3257","authenticated-orcid":false,"given":"Julia","family":"Dietz","sequence":"first","affiliation":[{"name":"Department of Internal 1 University Hospital Goethe University Frankfurt Germany"},{"name":"German Center for Infection Research (DZIF), External Partner Site Frankfurt 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Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Antoni","sequence":"additional","affiliation":[{"name":"Department of Medicine II Heidelberg University Hospital at Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology Charit\u00e9 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-1938","authenticated-orcid":false,"given":"Julian","family":"Schulze zur Wiesch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site, Hamburg-L\u00fcbeck-Borstel-Riems Hamburg 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