{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:02:45Z","timestamp":1792587765356,"version":"4.5.0"},"reference-count":36,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>The presence of pre-existing hepatitis C virus (HCV) resistance-associated substitutions (RASs) could attenuate viral susceptibility to direct-acting antiviral agents. The aim of this study was to better understand the differences among HCV RASs over time. We compared the prevalence and characteristics of naturally occurring HCV RASs in the NS3, NS5A, and NS5B genes between 2008 and 2016 in Chinese patients chronically infected with HCV genotypes (GT) 1b, 2a, 3a, 3b, and 6a.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>HCV RNA was extracted after serum samples were collected from 242 patients at treatment baseline, including 120 samples in 2008 and 122 samples in 2016. Reverse transcription and nested PCR were performed, and the PCR products of the NS3, NS5A, and NS5B regions were sequenced using the Sanger sequencing method. Finally, RASs were identified from the different viral strains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In GT1b, the overall frequency of NS5A RASs in 2016 was significantly higher than that in 2008 (42.0% vs. 18.4%;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.002). Among NS5A RASs, the most frequently detected RAS was Y93H (5.3% in 2008 vs. 15.9% in 2016;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.035), which confers medium- to high-level resistance to the NS5A inhibitors: daclatasvir (DCV), ledipasvir (LDV), ombitasvir (OMV), and elbasvir. The frequency of NS5A L28 (low-level resistance to DCV\/LDV\/OMV) in 2016 was also higher than that in 2008 (11.6% vs. 1.3%;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.027). In addition, the highest frequency of clinically relevant NS3 RASs was S122G\/A\/T (69.7% in 2008 and 72.5% in 2016) in HCV GT1b isolates, which had medium-level resistance to simeprevir and asunaprevir, followed by Y56F (7.9% in 2008 and 14.5% in 2016), which confers resistance to paritaprevir. Although NS5B C316N had the highest substitution rate in GT1b (80.2% in 2008 and 91.3% in 2016), it was associated with low-level resistance to sofosbuvir and dasabuvir. However, HCV RASs were rarely detectable at baseline in other genotypes or subtypes except GT1b in this study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The frequency of NS5A RASs in 2016 was significantly higher than that in 2008, especially at the L28 and Y93 substitution positions, which may be due to their better fitness compared with wild-type viruses.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/mdr.2018.0360","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T11:36:43Z","timestamp":1548934603000},"page":"944-950","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Comparison of Naturally Occurring Resistance-Associated Substitutions Between 2008 and 2016 in Chinese Patients with Chronic Hepatitis C Virus Infection"],"prefix":"10.1177","volume":"25","author":[{"given":"Wei","family":"Huang","sequence":"first","affiliation":[{"name":"Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjie","family":"Wang","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiming","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demin","family":"Yu","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peizhan","family":"Chen","sequence":"additional","affiliation":[{"name":"Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Lin","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Han","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Su","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fu Dan University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, East Hospital, Tongji University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Laboratory of Clinical Virology, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China."},{"name":"Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiaotong University, School of Medicine, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,7,11]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jhep.2016.09.001","article-title":"EASL Recommendations on Treatment of Hepatitis C 2016","volume":"66","author":"European Association for the Study of the Liver. 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