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Clonal evolution of multidrug resistant hepatitis B virus during entecavir rescue therapy

DC FieldValueLanguage
dc.contributor.author김도영-
dc.contributor.author김승택-
dc.contributor.author남정모-
dc.contributor.author박전한-
dc.contributor.author박준용-
dc.contributor.author안상훈-
dc.contributor.author전영은-
dc.contributor.author한광협-
dc.date.accessioned2018-03-26T16:49:43Z-
dc.date.available2018-03-26T16:49:43Z-
dc.date.issued2015-
dc.identifier.issn1478-3223-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/156858-
dc.description.abstractBACKGROUND & AIMS: Analysing the mutation pattern of multidrug resistance (MDR) is important in the treatment of chronic hepatitis B (CHB). In this study, the evolutionary pattern of MDR mutations was investigated in patients receiving entecavir (ETV) rescue therapy. METHODS: Eight CHB patients with lamivudine (LAM)- and adefovir (ADV)-resistant mutations showing suboptimal response to ETV and to subsequent ETV-plus-ADV therapy were enrolled. The clonal evolution of the mutation pattern was investigated through direct sequencing, multiplex restriction fragment mass polymorphism (RFMP), and clonal analysis and the utility of these methods was compared. RESULTS: Among 160 clones at baseline, wild-type hepatitis B virus (HBV) was present in 62 (38.8%), LAM-resistant mutations in 92 (57.6%) and ADV-resistant mutations in 55 (34.4%). LAM-resistant mutations increased to 70.6% at the end of ETV therapy and increased to 74.4% at the 12th month of ETV-plus-ADV therapy. During the same time periods, ETV-resistant mutations were present in 46.3% and 38.8%, and ADV-resistant 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 RFMP detected 73 mutations (28.5%). The sensitivity (73.1%, 95% CI; 64.1-82.1%) and specificity (96.9%, 95% CI; 94.4-99.4%) of RFMP 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 RFMP. CONCLUSIONS: The clonal evolution of the mutation pattern in MDR HBV showed the selection of LAM-resistant (±ETV-resistant) HBV during ETV rescue therapy, which may be the primary reason for patients' suboptimal response. Multiplex RFMP is a useful method for detecting MDR mutations in clinical practice.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherWiley-Blackwell-
dc.relation.isPartOfLiver International-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdenine/analogs & derivatives-
dc.subject.MESHAdenine/therapeutic use-
dc.subject.MESHAdult-
dc.subject.MESHAntiviral Agents/therapeutic use*-
dc.subject.MESHClonal Evolution/genetics*-
dc.subject.MESHDNA, Viral/genetics-
dc.subject.MESHDrug Resistance, Viral/genetics*-
dc.subject.MESHDrug Therapy, Combination-
dc.subject.MESHGenotype-
dc.subject.MESHGuanine/analogs & derivatives*-
dc.subject.MESHGuanine/therapeutic use-
dc.subject.MESHHepatitis B virus/genetics*-
dc.subject.MESHHepatitis B, Chronic/drug therapy*-
dc.subject.MESHHumans-
dc.subject.MESHLamivudine/therapeutic use-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHMutation-
dc.subject.MESHOrganophosphonates/therapeutic use-
dc.subject.MESHViral Load-
dc.titleClonal evolution of multidrug resistant hepatitis B virus during entecavir rescue therapy-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Internal Medicine-
dc.contributor.googleauthorYoung E. Chon-
dc.contributor.googleauthorBora Jin-
dc.contributor.googleauthorSang H. Ahn-
dc.contributor.googleauthorSeungtaek Kim-
dc.contributor.googleauthorNam D. Kim-
dc.contributor.googleauthorJeon H. Park-
dc.contributor.googleauthorChung M. Nam-
dc.contributor.googleauthorKyun-Hwan Kim-
dc.contributor.googleauthorSun P. Hong-
dc.contributor.googleauthorSung H. Choi-
dc.contributor.googleauthorDo Y. Kim-
dc.contributor.googleauthorJun Y. Park-
dc.contributor.googleauthorKwang-Hyub Han-
dc.identifier.doi10.1111/liv.12845-
dc.contributor.localIdA00385-
dc.contributor.localIdA00661-
dc.contributor.localIdA01264-
dc.contributor.localIdA01641-
dc.contributor.localIdA01675-
dc.contributor.localIdA02226-
dc.contributor.localIdA03532-
dc.contributor.localIdA04268-
dc.relation.journalcodeJ02171-
dc.identifier.eissn1478-3231-
dc.identifier.pmid25872678-
dc.identifier.urlhttp://onlinelibrary.wiley.com/doi/10.1111/liv.12845/abstract-
dc.subject.keywordchronic hepatitis B-
dc.subject.keywordclonal analysis-
dc.subject.keywordcolocation-
dc.subject.keyworddrug resistance-
dc.subject.keywordentecavir-
dc.subject.keywordhepatitis B virus-
dc.subject.keywordmultidrug resistance-
dc.contributor.alternativeNameKim, Do Young-
dc.contributor.alternativeNameKim, Seung Taek-
dc.contributor.alternativeNameNam, Jung Mo-
dc.contributor.alternativeNamePark, Jeon Han-
dc.contributor.alternativeNamePark, Jun Yong-
dc.contributor.alternativeNameAhn, Sang Hoon-
dc.contributor.alternativeNameChon, Young Eun-
dc.contributor.alternativeNameHan, Kwang Hyup-
dc.contributor.affiliatedAuthorKim, Do Young-
dc.contributor.affiliatedAuthorKim, Seung Taek-
dc.contributor.affiliatedAuthorNam, Jung Mo-
dc.contributor.affiliatedAuthorPark, Jeon Han-
dc.contributor.affiliatedAuthorPark, Jun Yong-
dc.contributor.affiliatedAuthorAhn, Sang Hoon-
dc.contributor.affiliatedAuthorChon, Young Eun-
dc.contributor.affiliatedAuthorHan, Kwang Hyup-
dc.citation.volume35-
dc.citation.number11-
dc.citation.startPage2370-
dc.citation.endPage2383-
dc.identifier.bibliographicCitationLiver International, Vol.35(11) : 2370-2383, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers

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