{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:50:29Z","timestamp":1777503029524,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T00:00:00Z","timestamp":1571616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572043"],"award-info":[{"award-number":["81572043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009331","name":"Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support","doi-asserted-by":"publisher","award":["ZYLX201707"],"award-info":[{"award-number":["ZYLX201707"]}],"id":[{"id":"10.13039\/501100009331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tenofovir disoproxil fumarate (TDF) imposes a high genetic barrier to drug resistance and potently inhibits replication of multidrug\u2010resistant hepatitis B virus. Few clinical cases with confirmed TDF\u2010resistance have been reported to date.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>Here, we report viral rebound in a patient with chronic hepatitis B who underwent TDF monotherapy and harboured a quadruple mutant consisting of classic entecavir (ETV)\u2010resistance mutations (rtL180M\/T184L\/M204V) together with an rtA200V mutation in the reverse transcriptase gene. Sequencing analysis revealed that this quadruple mutant emerged as a major viral population. In vitro phenotyping demonstrated that the rtL180M\/T184L\/A200V\/M204V mutant had moderate resistance to TDF treatment, with a 4.52\u2010fold higher half maximal effective concentration than that of wild\u2010type virus. Importantly, this patient with TDF resistance achieved virological suppression after TDF\/ETV combination rescue therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>An rtL180M\/T184L\/A200V\/M204V mutant with moderate resistance to TDF monotherapy was selected during sequential nucleoside analogue (NA) treatment in a stepwise manner. ETV\/TDF combination therapy effectively suppressed replication of this TDF\u2010resistant mutant. Our studies provide novel insights into the treatment of NA\u2010na\u00efve patients as well as patients with TDF resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.14241","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T09:24:51Z","timestamp":1568021091000},"page":"83-91","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Entecavir resistance mutations rtL180M\/T184L\/M204V combined with rtA200V lead to tenofovir resistance"],"prefix":"10.1111","volume":"40","author":[{"given":"Dong","family":"Jiang","sequence":"first","affiliation":[{"name":"Institute of Infectious Diseases Beijing Ditan Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Emerging infectious Diseases Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Peking University People's Hospital Peking University Hepatology Institute Beijing China"},{"name":"Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuesen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases Beijing Ditan Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Emerging infectious Diseases Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-3391","authenticated-orcid":false,"given":"Yuxin","family":"Li","sequence":"additional","affiliation":[{"name":"Center of Integrative Medicine Beijing Ditan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center of Integrative Medicine Beijing Ditan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases Beijing Ditan Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Emerging infectious Diseases Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7456-6061","authenticated-orcid":false,"given":"Hui","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Infectious Diseases Beijing Ditan Hospital Capital Medical University Beijing China"},{"name":"Beijing Key Laboratory of Emerging infectious Diseases Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3593-5741","authenticated-orcid":false,"given":"Xianbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Integrative Medicine Beijing Ditan Hospital Capital Medical University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2010.05.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033364"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.8559"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2893.2008.00966.x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00939-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.06.055"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22323"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22841"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2015.09.038"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12842"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1270-5"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2732"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.13331"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.05.024"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP3169"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.24153"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13294"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26686"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12613"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.027"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2007.02.001"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.02.006"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2294"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.23982"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2014.20.3.261"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308353"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2012.12.007"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22790"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29187"},{"key":"e_1_2_9_31_1","first-page":"497","article-title":"Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance","volume":"3","author":"Kim DY","year":"2017","journal-title":"J Med Virol"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2014.03.018"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12343"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2775"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20723"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02395-06"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867322666150904144802"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1159\/000360940"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14241","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.14241","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14241","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T06:32:02Z","timestamp":1694241122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.14241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,21]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/liv.14241"],"URL":"https:\/\/doi.org\/10.1111\/liv.14241","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/632984","asserted-by":"object"}]},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,21]]},"assertion":[{"value":"2019-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}