{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T23:17:33Z","timestamp":1709075853366},"reference-count":25,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A 1-year trial with entecavir plus adefovir resulted in a rate of virological response (VR) higher than that seen with lamivudine plus adefovir in multiple-drug-refractory chronic hepatitis B (CHB) patients. This extension study enrolled 89 of 90 patients who completed a 52-week randomized trial comparing treatment with entecavir plus adefovir (EA) to treatment with lamivudine plus adefovir (LA). At the baseline of the original study, all patients had lamivudine-resistant hepatitis B virus (HBV) and serum HBV DNA &gt; 2,000 IU\/ml despite prior lamivudine plus adefovir therapy. Of the 89 enrolled patients, 45 initially randomized to receive entecavir plus adefovir and the other 44 randomized to receive lamivudine plus adefovir received entecavir plus adefovir for an additional 52 weeks (EA-EA and LA-EA, respectively). The proportions of patients with a VR (serum HBV DNA &lt; 60 IU\/ml) gradually increased in both groups and were comparable at week 104 (42.2% in the EA-EA group and 34.1% in the LA-EA group;<jats:italic>P<\/jats:italic>= 0.51). The mean reductions in serum HBV DNA from baseline in the two groups were similar (\u22122.8 log<jats:sub>10<\/jats:sub>IU\/ml and \u22122.8 log<jats:sub>10<\/jats:sub>IU\/ml, respectively;<jats:italic>P<\/jats:italic>= 0.87). At week 104, the number of patients who retained the preexisting HBV mutants resistant to adefovir or entecavir had decreased from 8 to 2 in the EA-EA group and from 15 to 6 in the LA-EA group (<jats:italic>P<\/jats:italic>= 0.27). Both study groups had favorable safety profiles. In conclusion, up to 104 weeks of entecavir plus adefovir treatment was associated with a progressive VR, a decrease of levels of preexisting drug-resistant mutants, and no selection for additional resistance mutants of HBV in multiple-drug-refractory CHB patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01023217.)<\/jats:p>","DOI":"10.1128\/aac.00587-13","type":"journal-article","created":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T03:58:33Z","timestamp":1367899113000},"page":"3369-3374","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Randomized Trial of the Virologic Response during up to Two Years of Entecavir-Adefovir Combination Therapy in Multiple-Drug-Refractory Chronic Hepatitis B Virus Patients"],"prefix":"10.1128","volume":"57","author":[{"given":"Young-Suk","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danbi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Hyun","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Chu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Jin","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.05.013"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69347-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.1.65"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.016"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23785"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033364"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23061"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840400418"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23327"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24078"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.10.051"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21534"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.08.079"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.03.020"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23145"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.223206"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23246"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00338-12"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1914"},{"key":"e_1_3_2_21_2","first-page":"392A","article-title":"Entecavir+adefovir versus lamivudine+adefovir or entecavir alone in lamivudine-resistant chronic hepatitis B: 96-week data from the DEFINE study","volume":"56","author":"Heo J","year":"2012","unstructured":"HeoJ AhnSH KweonYO KimBH ChanHL-Y HorbanA WongcharatraweeS LlamosoC LeeKS. 2012. 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