{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T15:47:18Z","timestamp":1781279238738,"version":"3.54.1"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,2,7]],"date-time":"2016-02-07T00:00:00Z","timestamp":1454803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Sequential therapy posed a high risk of emergence of multidrug resistance and presented a management issue in chronic hepatitis <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>) treatment. We evaluated the antiviral efficacy and safety of entecavir (<jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>) plus tenofovir (<jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content>) combination therapy in multidrug\u2010resistant (<jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective, multicentre study, <jats:styled-content style=\"fixed-case\">MDR CHB<\/jats:styled-content> patients, defined as measurable serum <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> (\u226560 IU\/ml) while on any rescue treatment regimen for at least 24 weeks and the presence of documented prior genotypic resistance to both nucleoside analogue(s) and nucleotide analogue, were treated with <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content> 1.0 mg and <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> 300 mg combination therapy for 48 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 64 eligible patients who had previously failed to a median three lines of antiviral therapy (range, 2\u20136) were included. At baseline, median age was 47.0 years, 89.1% were <jats:styled-content style=\"fixed-case\">HB<\/jats:styled-content>eAg(+), and median <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> was 4.24 (range, 2.11\u20136.73) log<jats:sub>10<\/jats:sub> IU\/ml. By week 4, 12, 24 and 48, 15\/64 (23.4%), 36\/64 (56.3%), 43\/64 (67.2%) and 55\/64 (85.9%) patients achieved a <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> &lt;60 IU\/ml respectively. The mean reduction of <jats:styled-content style=\"fixed-case\">HBV DNA<\/jats:styled-content> from baseline to 4 and 48 weeks was 1.23 log<jats:sub>10<\/jats:sub> IU\/ml and 2.38 log<jats:sub>10<\/jats:sub> IU\/ml respectively. Although five patients experienced virological breakthrough, all were transient and no resistant mutation to <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> or novel mutation was detected in any patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In difficult\u2010to\u2010treat <jats:styled-content style=\"fixed-case\">MDR CHB<\/jats:styled-content> patients with a high exposure to multiple antiviral drugs, <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content> plus <jats:styled-content style=\"fixed-case\">TDF<\/jats:styled-content> combination therapy can provide a very high rate of viral suppression through 48 weeks of treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.13059","type":"journal-article","created":{"date-parts":[[2016,1,19]],"date-time":"2016-01-19T13:27:08Z","timestamp":1453210028000},"page":"1108-1115","source":"Crossref","is-referenced-by-count":19,"title":["Entecavir plus tenofovir combination therapy in patients with multidrug\u2010resistant chronic hepatitis <scp>B<\/scp>: results of a multicentre, prospective study"],"prefix":"10.1111","volume":"36","author":[{"given":"Jun Yong","family":"Park","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Wook","family":"Kim","sequence":"additional","affiliation":[{"name":"Liver Cirrhosis Clinical Research Center Seoul Korea"},{"name":"Department of Internal Medicine Uijeongbu St. Mary's Hospital The Catholic University of Korea College of Medicine Uijeongbu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Hyun","family":"Bae","sequence":"additional","affiliation":[{"name":"Liver Cirrhosis Clinical Research Center Seoul Korea"},{"name":"Department of Internal Medicine Seoul St. Mary's Hospital The Catholic University of Korea College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Sik","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Liver Cirrhosis Clinical Research Center Seoul Korea"},{"name":"Department of Internal Medicine Uijeongbu St. Mary's Hospital The Catholic University of Korea College of Medicine Uijeongbu Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Kew","family":"Yoon","sequence":"additional","affiliation":[{"name":"Liver Cirrhosis Clinical Research Center Seoul Korea"},{"name":"Department of Internal Medicine Seoul St. Mary's Hospital The Catholic University of Korea College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang\u2010Hyub","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Seoul 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