Zeng Ai-Zhong, Lu Ping, Deng Hui, Cai Su-Fang, Yang Chun, Xin Xiao-Juan, Guo Jin-Jun, Li Qing-Ling, Deng Xiao-Hui, Huang Ai-Long
Department of Infectious Disease, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Zhonghua Gan Zang Bing Za Zhi. 2009 Oct;17(10):730-4.
To explore the mechanism for adefovir dipivoxil (ADV) resistance occurred in chronic hepatitis B patients of a series of phase III clinical trails.
30 resistant HBV strains 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 nucleotide sequence of HBV strains deposited in GeneBank.
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 secondary 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.
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.
探讨一系列Ⅲ期临床试验中慢性乙型肝炎患者出现阿德福韦酯（ADV）耐药的机制。
从177例接受ADV治疗的慢性乙型肝炎患者中筛选出30株耐药HBV毒株。采用巢式PCR扩增HBV聚合酶RT区，并与GeneBank中保存的HBV毒株标准核苷酸序列进行分析。
30株HBV毒株中21株为原发性耐药毒株，其中5株（23.8%，5/21）有rtN118H多态性位点。另外9株HBV毒株表现为继发性耐药，在保守区C（rtM207V）及其他非保守区发现变异。未发现rtN236T和rtA181V/T等经典突变位点。
rtN118H多态性位点可能是HBV对ADV治疗原发性耐药的原因。HBV RT C结构域的rtM207V变异及其他变异位点可能在HBV对ADV治疗的继发性耐药中起作用，天然耐药准种可能是ADV快速耐药的基础。这些结论有待表型试验进一步证实。
