{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T05:48:40Z","timestamp":1695620920174},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T00:00:00Z","timestamp":1431475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Yonsei Liver Blood Bank"},{"name":"sanofiaventis Korea"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Analysing the mutation pattern of multidrug resistance (<jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content>) is important in the treatment of chronic hepatitis <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content>). In this study, the evolutionary pattern of <jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content> mutations was investigated in patients receiving entecavir (<jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>) rescue therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eight <jats:styled-content style=\"fixed-case\">CHB<\/jats:styled-content> patients with lamivudine (<jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content>)\u2010 and adefovir (<jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content>)\u2010resistant mutations showing suboptimal response to <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content> and to subsequent <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>\u2010plus\u2010<jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content> therapy were enrolled. The clonal evolution of the mutation pattern was investigated through direct sequencing, multiplex restriction fragment mass polymorphism (<jats:styled-content style=\"fixed-case\">RFMP<\/jats:styled-content>), and clonal analysis and the utility of these methods was compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 160 clones at baseline, wild\u2010type hepatitis <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content> virus (<jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content>) was present in 62 (38.8%), <jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content>\u2010resistant mutations in 92 (57.6%) and <jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content>\u2010resistant mutations in 55 (34.4%). <jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content>\u2010resistant mutations increased to 70.6% at the end of <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content> therapy and increased to 74.4% at the 12th month of <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>\u2010plus\u2010<jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content> therapy. During the same time periods, <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>\u2010resistant mutations were present in 46.3% and 38.8%, and <jats:styled-content style=\"fixed-case\">ADV<\/jats:styled-content>\u2010resistant mutations were present in 3.1% and 9.4% respectively. When 256 nucleotides from 32 samples were examined for mutations, clonal analysis detected 93 mutations (36.3%), direct sequencing detected 36 mutations (14.1%) and <jats:styled-content style=\"fixed-case\">RFMP<\/jats:styled-content> detected 73 mutations (28.5%). The sensitivity (73.1%, 95% CI; 64.1\u201382.1%) and specificity (96.9%, 95% CI; 94.4\u201399.4%) of <jats:styled-content style=\"fixed-case\">RFMP<\/jats:styled-content> were high, showing a concordance rate of 88.3% with the results from clonal analysis. All mutations exceeding 40% of the total clones detected by clonal analysis were also detected by <jats:styled-content style=\"fixed-case\">RFMP<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The clonal evolution of the mutation pattern in <jats:styled-content style=\"fixed-case\">MDR HBV<\/jats:styled-content> showed the selection of <jats:styled-content style=\"fixed-case\">LAM<\/jats:styled-content>\u2010resistant (\u00b1<jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content>\u2010resistant) <jats:styled-content style=\"fixed-case\">HBV<\/jats:styled-content> during <jats:styled-content style=\"fixed-case\">ETV<\/jats:styled-content> rescue therapy, which may be the primary reason for patients' suboptimal response. Multiplex <jats:styled-content style=\"fixed-case\">RFMP<\/jats:styled-content> is a useful method for detecting <jats:styled-content style=\"fixed-case\">MDR<\/jats:styled-content> mutations in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12845","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T05:02:53Z","timestamp":1429074173000},"page":"2370-2383","source":"Crossref","is-referenced-by-count":2,"title":["Clonal evolution of multidrug resistant hepatitis <scp>B<\/scp> virus during entecavir rescue therapy"],"prefix":"10.1111","volume":"35","author":[{"given":"Young E.","family":"Chon","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Yonsei University Health System Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bora","family":"Jin","sequence":"additional","affiliation":[{"name":"Brain Korea 21 plus Project for Medical Science Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang H.","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Yonsei University Health System Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seungtaek","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Severance Biomedical Science Institute Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nam D.","family":"Kim","sequence":"additional","affiliation":[{"name":"New Drug Development Center Daegu\u2010Gyeongbuk Medical Innovation Foundation Daegu Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeon H.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung M.","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyun\u2010Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Cancer Research and Diagnostic Medicine IBST School of Medicine Konkuk University Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun P.","family":"Hong","sequence":"additional","affiliation":[{"name":"Research and Development Center GeneMatrix Inc. Seongnam Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung H.","family":"Choi","sequence":"additional","affiliation":[{"name":"Brain Korea 21 plus Project for Medical Science Yonsei University College of Medicine Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Do Y.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Yonsei University Health System Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun Y.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Yonsei University College of Medicine Seoul Korea"},{"name":"Liver Cirrhosis Clinical Research Center Yonsei University Health System Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 Yonsei University Health System Seoul Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,5,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199712113372406"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.016"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.295.1.65"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23190"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.010"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21698"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.077099"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.10.018"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.03.020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.23440"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.01.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1702"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1177\/135965350501000306","article-title":"Evaluation of methods for monitoring drug resistance in chronic hepatitis B patients during lamivudine therapy based on mass spectrometry and reverse hybridization","volume":"10","author":"Kim H","year":"2005","journal-title":"Antivir Ther"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61425-1"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.01.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21189"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12069"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)60012-9"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules15095878"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009195"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01061-09"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20723"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21290"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2008.05570.x"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12845","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fliv.12845","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.12845","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T14:50:49Z","timestamp":1695567049000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.12845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,13]]},"references-count":24,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1111\/liv.12845"],"URL":"https:\/\/doi.org\/10.1111\/liv.12845","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,13]]}}}