中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2009年
10期
730-734
,共5页
曾爱中%卢萍%邓蕙%蔡素芳%杨春%辛小娟%郭进军%李青岭%邓小燕%黄爱龙
曾愛中%盧萍%鄧蕙%蔡素芳%楊春%辛小娟%郭進軍%李青嶺%鄧小燕%黃愛龍
증애중%로평%산혜%채소방%양춘%신소연%곽진군%리청령%산소연%황애룡
肝炎%乙型%慢性%阿德福韦酯%耐药%准种
肝炎%乙型%慢性%阿德福韋酯%耐藥%準種
간염%을형%만성%아덕복위지%내약%준충
Hepatitis B%chronic%Adefovir dipivoxil%Resistance%Quasispecies
目的 探讨阿德福韦酯治疗慢性乙型肝炎耐药性产生的原因.方法 从阿德福韦酯Ⅲ期临床试验中筛选出30例原发治疗失败或继发耐药患者,应用巢式逆转录聚合酶链反应扩增HBVRT区,比对RT区核苷酸及氨基酸序列,找出变异位点.结果 30株阿德福韦酯治疗失败者中有21株HBV表现出原发性耐药,其中5株具有多态性位点rtN118H(23.8%,5/21).另外9株发生继发性耐药,继发耐药毒株在RT保守区(C结构域rtM207V)和非保守区多个区域均有变异.没有发现典型的nN236T和rtA181V/T突变.结论 多态性位点rtN118H与阿德福韦酯原发耐药可能有关.HBV RT C结构域rtM207V变异及其他处于非保守区的变异可能与HBV继发性耐药有关,天然耐药准种的存在可能是HBV对阿德福韦酯迅速耐药(继发性)的基础.上述结论 有待进一步表型验证实验加以证实.
目的 探討阿德福韋酯治療慢性乙型肝炎耐藥性產生的原因.方法 從阿德福韋酯Ⅲ期臨床試驗中篩選齣30例原髮治療失敗或繼髮耐藥患者,應用巢式逆轉錄聚閤酶鏈反應擴增HBVRT區,比對RT區覈苷痠及氨基痠序列,找齣變異位點.結果 30株阿德福韋酯治療失敗者中有21株HBV錶現齣原髮性耐藥,其中5株具有多態性位點rtN118H(23.8%,5/21).另外9株髮生繼髮性耐藥,繼髮耐藥毒株在RT保守區(C結構域rtM207V)和非保守區多箇區域均有變異.沒有髮現典型的nN236T和rtA181V/T突變.結論 多態性位點rtN118H與阿德福韋酯原髮耐藥可能有關.HBV RT C結構域rtM207V變異及其他處于非保守區的變異可能與HBV繼髮性耐藥有關,天然耐藥準種的存在可能是HBV對阿德福韋酯迅速耐藥(繼髮性)的基礎.上述結論 有待進一步錶型驗證實驗加以證實.
목적 탐토아덕복위지치료만성을형간염내약성산생적원인.방법 종아덕복위지Ⅲ기림상시험중사선출30례원발치료실패혹계발내약환자,응용소식역전록취합매련반응확증HBVRT구,비대RT구핵감산급안기산서렬,조출변이위점.결과 30주아덕복위지치료실패자중유21주HBV표현출원발성내약,기중5주구유다태성위점rtN118H(23.8%,5/21).령외9주발생계발성내약,계발내약독주재RT보수구(C결구역rtM207V)화비보수구다개구역균유변이.몰유발현전형적nN236T화rtA181V/T돌변.결론 다태성위점rtN118H여아덕복위지원발내약가능유관.HBV RT C결구역rtM207V변이급기타처우비보수구적변이가능여HBV계발성내약유관,천연내약준충적존재가능시HBV대아덕복위지신속내약(계발성)적기출.상술결론 유대진일보표형험증실험가이증실.
Objective To explore the mechanism for adefovir dipivoxil (ADV) resistance occurred in chronic hepatitis B patients of a series of phase Ⅲ clinical trails. Methods 30 resistant HBV swains were selected out from 177 cases of ADV treated chronic hepatitis B patients. HBV polymerase RT region were amplified by nested PCR and analyzed with the standard neucleiotide sequence of HBV strains deposited in GeneBank. Results 21 out of 30 HBV strains were primary resistant strains, among them 5 HBV strains (23.8 %, 5/21) had the polymorphism site of rtN118H. While the other 9 HBV strains showed second-ary resistance, variations in conservative region C (rtM207V) and other non-conservative regions were found. The classic mutation sites such as rtN236T and rtA181V/T were not found. Conclusions Polymorphism site of rtN118H might be responsible for HBV primary resistance to ADV therapy, rtM207V variation in HBV RT C domain and other variation sites might play a role in HBV secondary resistance to ADV treatment, and natural resistant quasispecies may be the basis for the ADV quick resistance. These conclusions await further confirmation by phenotype test.
