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Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients

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dc.contributor.author조, 진희-
dc.contributor.author정, 재연-
dc.contributor.author강, 준구-
dc.contributor.author박, 진선-
dc.contributor.author이, 명희-
dc.contributor.author임, 남규-
dc.contributor.author홍, 선표-
dc.contributor.author김, 수옥-
dc.contributor.author유, 왕돈-
dc.contributor.author조, 성원-
dc.date.accessioned2014-01-21T01:54:16Z-
dc.date.available2014-01-21T01:54:16Z-
dc.date.issued2008-
dc.identifier.issn1738-222X-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/9018-
dc.description.abstractBackground : Adefovir dipivoxil (adefovir) effectively inhibits both wild-type and lamivudine-resistant hepatitis B virus (HBV) replication. The development of adefovir resistance is both delayed and infrequent compared with lamivudine resistance. The aim of this study was to characterize the serologic, biochemical, and virologic response to adefovir, and to explore the factors affecting initial virologic response (IVR, defined as a decrease in serum HBV below 4 log10copies/mL after 6 month of treatment) and adefovir resistance in lamivudine resistant HBV-infected patients.



Methods : This study population comprised 76 patients with lamivudine-resistance who had received adefovir for more than 12 months between March 2004 and December 2006. The adefovir-resistant mutant was assayed at 6 months and 12 months during adefovir administration. Restriction- fragment mass polymorphism analysis was used for detecting YMDD and adefovir mutants.



Results : After adefovir administration, an IVR was observed in 31% of the patients with lamivudine resistance. Factors associated with an IVR were HBeAg negativity (P=0.04) and the presence of liver cirrhosis (P=0.04). Age, sex, pretreatment levels of alanine aminotransferase and aspartate aminotransferase, pretreatment HBV DNA levels, presence of precore mutation, and type of YMDD mutants were not related to an IVR during adefovir treatment. The prevalence of adefovir resistance was 5% and 13% at 6 months and 12 months after therapy, respectively. Mixed infection of the precore mutant was a risk factors for the emergence of adefovir resistance (P=0.01).



Conclusion : Lamivudine-resistant HBV patients exhibiting HBeAg negativity and liver cirrhosis were more likely to achieve an IVR after adefovir therapy. Adefovir resistance was associated with mixed infection of the precore mutant.
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dc.description.abstract배 경 : 아데포비어는 뉴클레오티드 유사체로 초치료 및 라미부딘 내성 환자에서 효과적으로 HBV 바이러스 증식을 억제한다. 아데포비어는 라미부딘 내성과 비교해 그 빈도가 낮다. 목적: 본 연구에서는 라미부딘 내성 만성 B형간염 환자에서 아데포비어 투여에 따른 혈청학적, 생화학적, 초기 바이러스반응, 그리고 내성 발생을 규명하고자 본 연구를 시행하였다.



방 법 : 2004년 3월부터 2006년 12월까지 라미부던 내성 환자에서 1년 이상 아데포비어 l0mg을 복용한 환자를 대상으로 하였다. 아데포비어 투여 직전 및 투여 후 1년간 3개월 간격으로 HBeAg, anti-HBe, ALT, AST, HBV DNA를 측정하였고, 모든 환자에서 아데포비어 투여 6개월, 12개월에 adefovir 변이종(rtA181 V IT, rtN-236T)을 분석하였다. HBV DNA는 b-DNA법을 YMDD 변이종과 adefovir 변이종은 RFMP법을 이용하였다.



결 과 : 아데포비어 투여 후 초기 바이러스반응은 31%에서 나타났고, HBeAg 음성(p= 0.04), 간경변증(P=0.04)이 있는 경우가 초기 바이러스반응이 흔하였다. 아데포비어 내성률은 6개월에 5%, 127~월에 13% 출현하였고, precore 변이종의 혼합감염(P=0.01)에서 아데포비어 내성률이 높았다.



결 론 : 라미부딘 내성 만성 B형간염 환자에서 HBeAg 음성, 간경변증이 있는 경우가 아데포비어에 대한 초기 바이러스반응이 잘 나타나고, pre-core 변이종의 혼합감염이 아데포비어 내성과 관계가 있었다.
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dc.language.isoko-
dc.titleFactors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients-
dc.title.alternative라미부딘 내성 만성 B형간염 환자에서 아데포비어 투여에 따른 내성 바이러스 출현 및 초기 바이러스반응에 미치는 인자-
dc.typeArticle-
dc.identifier.urlhttp://www.e-cmh.org/journal/view.php?number=2656-
dc.subject.keyword아데포비어-
dc.subject.keywordB형간염-
dc.subject.keyword리미부딘-
dc.subject.keyword약제내성-
dc.subject.keywordAdefovir-
dc.subject.keywordHepatitis B-
dc.subject.keywordLamivudine-
dc.subject.keywordDrug resistance-
dc.contributor.affiliatedAuthor정, 재연-
dc.contributor.affiliatedAuthor박, 진선-
dc.contributor.affiliatedAuthor조, 성원-
dc.type.localJournal Papers-
dc.citation.titleThe Korean journal of hepatology-
dc.citation.volume14-
dc.citation.number1-
dc.citation.date2008-
dc.citation.startPage58-
dc.citation.endPage66-
dc.identifier.bibliographicCitationThe Korean journal of hepatology, 14(1). : 58-66, 2008-
dc.identifier.eissn2093-8047-
dc.relation.journalidJ01738222X-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Gastroenterology
Journal Papers > School of Medicine / Graduate School of Medicine > Cardiology
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