{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:30:22Z","timestamp":1790069422404,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T00:00:00Z","timestamp":1542153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003323","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":[[2019,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Nucleoside and nucleotide analogues (<jats:styled-content style=\"fixed-case\">NUC<\/jats:styled-content>s) targeting hepatitis B virus are capable of selecting resistant viruses upon long\u2010term administration as monotherapies. The prevalence of resistance\u2010associated substitutions (RASs) and fitness\u2010associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment\u2010na\u00efve patients chronically infected with hepatitis B virus (<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>) consecutively referred for the first time to one of French reference centres were included. The nearly full\u2010length <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>s were detected in 25% of treatment\u2010na\u00efve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> resistance to currently approved <jats:styled-content style=\"fixed-case\">NUC<\/jats:styled-content>s or with increased fitness of resistant variants were affected, except position 80. <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>s at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with <jats:styled-content style=\"fixed-case\">RAS<\/jats:styled-content>s detectable by next\u2010generation sequencing at baseline who were treatment\u2010eligible and treated with currently recommended drugs achieved a virological response. The presence of pre\u2010existing <jats:styled-content style=\"fixed-case\">HBV RAS<\/jats:styled-content>s has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.<\/jats:p>","DOI":"10.1111\/jvh.13025","type":"journal-article","created":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T15:09:26Z","timestamp":1539961766000},"page":"278-286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6913-9017","authenticated-orcid":false,"given":"St\u00e9phane","family":"Chevaliez","sequence":"first","affiliation":[{"name":"Department of Virology H\u00f4pital Henri Mondor National Reference Center for Viral Hepatitis B, C and D Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"},{"name":"INSERM U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Virology H\u00f4pital Henri Mondor National Reference Center for Viral Hepatitis B, C and D Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"},{"name":"INSERM U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lila","family":"Poiteau","sequence":"additional","affiliation":[{"name":"Department of Virology H\u00f4pital Henri Mondor National Reference Center for Viral Hepatitis B, C and D Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"},{"name":"INSERM U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Soulier","sequence":"additional","affiliation":[{"name":"Department of Virology H\u00f4pital Henri Mondor National Reference Center for Viral Hepatitis B, C and D Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"},{"name":"INSERM U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Donati","sequence":"additional","affiliation":[{"name":"Department of Virology H\u00f4pital Henri Mondor National Reference Center for Viral Hepatitis B, C and D Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"},{"name":"INSERM U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Darty\u2010Mercier","sequence":"additional","affiliation":[{"name":"Department of Virology H\u00f4pital Henri Mondor National Reference Center for Viral Hepatitis B, C and D Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"},{"name":"INSERM U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Pioche","sequence":"additional","affiliation":[{"name":"Sant\u00e9 Publique France  Saint\u2010Maurice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Leroy","sequence":"additional","affiliation":[{"name":"Clinique d'H\u00e9patogastroent\u00e9rologie Centre Hospitalier Universitaire de Grenoble  Grenoble France"},{"name":"INSERM U823  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Brodard","sequence":"additional","affiliation":[{"name":"Laboratoire de Virologie H\u00f4pital Robert Debr\u00e9  Reims France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-0083","authenticated-orcid":false,"given":"Fabien","family":"Zoulim","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9patogastroent\u00e9rologie Hospices Civils de Lyon  Lyon France"},{"name":"INSERM U1052, Cancer Research Center of Lyon (CRCL)  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Brouard","sequence":"additional","affiliation":[{"name":"Sant\u00e9 Publique France  Saint\u2010Maurice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Larsen","sequence":"additional","affiliation":[{"name":"Sant\u00e9 Publique France  Saint\u2010Maurice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Semaille","sequence":"additional","affiliation":[{"name":"Sant\u00e9 Publique France  Saint\u2010Maurice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Roudot\u2010Thoraval","sequence":"additional","affiliation":[{"name":"Department of Public Health H\u00f4pital Henri Mondor Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Michel","family":"Pawlotsky","sequence":"additional","affiliation":[{"name":"Department of Virology H\u00f4pital Henri Mondor National Reference Center for Viral Hepatitis B, C and D Universit\u00e9 Paris\u2010Est  Cr\u00e9teil France"},{"name":"INSERM U955  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Hepatology Reference Centers Laboratories Network for Chronic Hepatitis B Surveillance","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-014-3486-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26686"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12613"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1386-6532(05)80021-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.063"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.2.643-653.2006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26383"},{"key":"e_1_2_8_11_1","first-page":"5","article-title":"Surface gene variation of HBV: scientific and medical relavance","volume":"3","author":"Wallace LA","year":"1997","journal-title":"Vir Hep Rev"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.03.020"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.02.027"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.1897"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.08.020"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2016.10.014"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02229-15"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2403"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2813"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-016-2959-8"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001080"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00128-15"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.13025","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T19:14:56Z","timestamp":1694718896000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,14]]},"references-count":21,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1111\/jvh.13025"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13025","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,14]]},"assertion":[{"value":"2018-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}