{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:04:47Z","timestamp":1785168287381,"version":"3.55.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T00:00:00Z","timestamp":1500336000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T00:00:00Z","timestamp":1500336000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Combination therapy has been recommended for the treatment of patients harboring multiple drug\u2010resistant hepatitis B virus (HBV). However, we recently demonstrated that monotherapy with tenofovir disoproxil fumarate (TDF) for 48 weeks displayed noninferior efficacy to TDF plus entecavir (ETV) combination therapy in patients with HBV resistant to multiple drugs, including ETV and adefovir. Nonetheless, whether prolonged TDF monotherapy would be safe and increase the virologic response rate in these patients was unclear. Among 192 patients with HBV\u2010resistance mutations to ETV and\/or adefovir, who were randomized to receive TDF monotherapy (n = 95) or TDF\/ETV combination therapy (n = 97) for 48 weeks, 189 agreed to continue TDF monotherapy (TDF\u2010TDF group) or to switch to TDF monotherapy (TDF\/ETV\u2010TDF group) and 180 (93.8%) completed the 144\u2010week study. Serum HBV DNA &lt;15 IU\/mL at week 48, the primary efficacy endpoint, was achieved in 66.3% in the TDF\u2010TDF group and 68.0% in the TDF\/ETV\u2010TDF group (<jats:italic toggle=\"yes\">P =<\/jats:italic> 0.80). At week 144, the proportion with HBV DNA &lt;15 IU\/mL increased to 74.5%, which was significantly higher compared with that at week 48 (<jats:italic toggle=\"yes\">P =<\/jats:italic> 0.03), without a significant difference between groups (<jats:italic toggle=\"yes\">P =<\/jats:italic> 0.46). By on\u2010treatment analysis, a total of 79.4% had HBV DNA &lt;15 IU\/mL at week 144. Transient virologic breakthrough occurred in 6 patients, which was due to poor drug adherence. At week 144, 19 patients who had HBV DNA levels &gt;60 IU\/mL qualified for genotypic resistance analysis, and 6 retained some of their baseline resistance mutations of HBV. No patients developed additional resistance mutations throughout the study period. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: TDF monotherapy was efficacious and safe for up to 144 weeks, providing an increasing rate of virologic response in heavily pretreated patients with multidrug\u2010resistant HBV. (H<jats:sc>epatology<\/jats:sc> 2017;66:772\u2013783).<\/jats:p>","DOI":"10.1002\/hep.29187","type":"journal-article","created":{"date-parts":[[2017,3,30]],"date-time":"2017-03-30T10:29:41Z","timestamp":1490869781000},"page":"772-783","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Monotherapy with tenofovir disoproxil fumarate for multiple drug\u2010resistant chronic hepatitis B: 3\u2010year trial"],"prefix":"10.1097","volume":"66","author":[{"given":"Young\u2010Suk","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Gastroenterology,Liver Center, Asan Medical Center, University of Ulsan College of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Liver Center, Asan Medical Center, University of Ulsan College of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geum\u2010Youn","family":"Gwak","sequence":"additional","affiliation":[{"name":"Department of Medicine,Samsung Medical Center, Sungkyunkwan University School of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwan Soo","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Korea University College of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoon Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Liver Research Institute,Seoul National University College of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonggi","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Liver Center, Asan Medical Center, University of Ulsan College of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"An","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Liver Center, Asan Medical Center, University of Ulsan College of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Chu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,Liver Center, Asan Medical Center, University of Ulsan College of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Chul","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Konkuk University School of Medicine,Seoul,Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Konkuk University School of 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