{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:54:05Z","timestamp":1787507645195,"version":"build-2736575974"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T00:00:00Z","timestamp":1448409600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T00:00:00Z","timestamp":1448409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,1]]},"abstract":"\n Single\u2010nucleotide polymorphisms (SNPs) in the interferon lambda 4 (\n IFNL4<\/jats:italic>\n ) gene are predictors for treatment success in patients with hepatitis C virus (HCV) infection. For direct\u2010acting antiviral combinations only weak association with\n IFNL4<\/jats:italic>\n SNPs was observed. Little is known about potential selections of resistance\u2010associated variants (RAVs) by the\n IFNL4<\/jats:italic>\n genotype. This study analyzed the prevalence of RAVs to currently approved direct\u2010acting antivirals in a large European population in correlation to SNPs in\n IFNL4<\/jats:italic>\n . Samples of 633 patients chronically infected with HCV genotypes 1a (n = 259), 1b (n = 323), and 3 (n = 51) were genotyped for rs12979860 (formerly known as\n IL28B<\/jats:italic>\n ) and rs368234815. RAVs in\n NS3<\/jats:italic>\n ,\n NS5A<\/jats:italic>\n , and\n NS5B<\/jats:italic>\n were detected by population\u2010based sequencing. In addition,\n IFNL4<\/jats:italic>\n SNPs and\n NS5A<\/jats:italic>\n RAVs were analyzed including deep sequencing (n = 109) in an independent replication cohort of HCV genotype 1\u2010infected patients (n = 201). No significant correlation was found between\n IFNL4<\/jats:italic>\n SNPs and rare and common RAVs within\n NS3<\/jats:italic>\n and\n NS5B<\/jats:italic>\n . In contrast, the\n NS5A<\/jats:italic>\n RAV Y93H was detected frequently in HCV genotype 1b (14%) and significantly associated with the beneficial\n IFNL4<\/jats:italic>\n SNPs (\n P<\/jats:italic>\n < 0.001 and\n P<\/jats:italic>\n = 0.002, respectively). Moreover, the presence of Y93H in HCV genotype 1b patients was significantly associated with the second site variant T83M (\n P<\/jats:italic>\n < 0.001). Independent factors significantly associated with the presence of Y93H were\n IFNL4<\/jats:italic>\n genotype and high baseline viral load.\n Conclusion:<\/jats:italic>\n The\n NS5A<\/jats:italic>\n RAV Y93H is significantly associated with the presence of beneficial\n IFNL4<\/jats:italic>\n SNPs and a high baseline viral load in HCV genotype 1\u2010infected patients, which may explain a lack of correlation or even an inverse correlation of treatment response with\n IFNL4<\/jats:italic>\n genotype in some NS5A inhibitor containing IFN\u2010free regimens. (H\n epatology<\/jats:sc>\n 2016;63:63\u201373)\n <\/jats:p>","DOI":"10.1002\/hep.28255","type":"journal-article","created":{"date-parts":[[2015,9,25]],"date-time":"2015-09-25T19:28:42Z","timestamp":1443209322000},"page":"63-73","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":38,"title":["Interferon lambda 4 genotypes and resistance\u2010associated variants in patients infected with hepatitis C virus genotypes 1 and 3"],"prefix":"10.1097","volume":"63","author":[{"given":"Kai\u2010Henrik","family":"Peiffer","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Sommer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Susser","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Vermehren","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Institute of Biostatistics and Mathematical Modeling,J.W. Goethe University,Frankfurt,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"D\u00f6ring","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Applied Algorithmics,Max Planck Institute for Informatics,Saarbr\u00fccken,Germany"},{"name":"Graduate School of Computer Science,Saarbr\u00fccken,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Dietz","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dany","family":"Perner","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Berkowski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zeuzem","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Sarrazin","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2015,11,25]]},"reference":[{"issue":"Suppl. 1","key":"hep28255-bib-0001-20241017","first-page":"S45","article-title":"Global epidemiology and genotype distribution of the hepatitis C virus infection","volume":"61","year":"2014","journal-title":"J Hepatol"},{"key":"hep28255-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1038\/ng.449","article-title":"Genome\u2010wide association of IL28B with response to pegylated interferon\u2010alpha and ribavirin therapy for chronic 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