基因芯片检测拉米夫定治疗乙肝病毒感染耐药分析

目的 分析拉米夫定治疗乙肝病毒感染耐药性,旨在为指导慢性乙肝患者临床药物治疗提供新方法.方法 应用基因芯片检测255份51名拉米夫定抗乙肝病毒治疗自愿者不同阶段服药的临床标本及145份HBV DNA阴性血清耐药突变,并对突变进行分析.结果 经一年药物治疗10名患者产生耐药突变,耐药率19.6%（10/51）,产生突变阳性标本病毒载量＞105拷贝/ml.药物治疗后产生突变＞6个月.10例突变病毒株中,552密码子处突变9例,528密码子处突变3例,密码子555中未发现突变.5例血清存在混合感染,其中4例为野生型病毒与突变型的混合,野生型病毒所占比例皆在40%以下.1例血清出现在（4,4）位点的密码子ATT与（3,3）位点密码子TTG两种突变,两种突变类型病毒并行产生同步增长.（3,3）突变类型首次报道.结论 拉米夫定抗乙肝病毒治疗6个月以上易产生耐药,产生耐药病毒载量＞105拷贝/ml.主要发生在YMDD区,且存在两种突变类型病毒的混合感染,以上结果对慢性乙肝患者用药具有指导作用.

Evaluation of detecting resistant mutants in lamivudine treated HBV infected by gene chip

Objective To investigate of drug resistant mutants tend to be induced in the HBV infected patients treated by lamivudine in this paper, which contributes a new way to direct clinical drug administration. Methods 255 clinical samples from 51 patients treated with lamivudine and 145 sera from HBV DNA negative controls were assayed for HBV mutations utilizing gene chip and the mutations were analysed. Results 10 patients drug resistant mutants were detectd in all 51 patients HBV infected treated by lamivudine, and drug fast rate is19.6% ( 10/51 ), and its virus loading ＞ 105 copes/ml. 4 patients HBeAg were changed negative in the HBV infected patients treated by lamivudine. 10 HBV DNA polymerase mutation was detected, Its 9 mutantion in codon 552 ( YMDD convsev district), 3 mutantion in codon 528and none mutantion in codon 555. There are 4 eligible to detecting wild type HBV and HBV mutants in 5patient's sera and the lower 40% relative proportion of wild type HBV. Two mutantion type virus were detected the (4,4) codon ATT and (3,3) codon TTG in one patient's sera, and its emerged and increased synchronization. Previously unreported (3,3) mutants were found in those samples. Conclusion Upper six months were easily formed drug resistant mutants tend to be induced in the HBV infected patients treated by lamivudine, and its virus loading ＞105 copes/ml. The wild type HBV and HBV mutants mixed viruses infection of YMDD convsev district in patient's sera. The above studies has great potential application of administration for lamivudine treatment in HBV patients.