中文摘要：

目的研究恩替卡韦治疗后乙型肝炎病毒（HBV）多聚酶区基因变异情况。方法收集恩替卡韦治疗后出现HBV病毒学突破患者的血清，采用聚合酶链反应（PCR）产物直接测序，分析HBV—P区基因变异发生情况。结果29例患者中检出恩替卡韦基因型耐药19例，其中16例（84．2％，16／19）既往有拉米夫定治疗失败史；17例（58．6％，17／29）变异类型以rtLl80＋rtM204＋rtTl84为主；7例（24．1％，7／29）为B基因型，22例（75．9％，22／29）为c基因型。7例B基因型中检出恩替卡韦基因型耐药者4例（57．1％），22例C基因型中检出恩替卡韦基因型耐药者15例（68．2％），差异无统计学意义（P=0．665）。结论恩替卡韦基因型耐药多出现于拉米夫定治疗失败后序贯治疗，rtLl80＋rtM204＋rtTl84蛮异类型在B和C慕因型的恩替卡韦耐药中较为常见。

英文摘要：

Objective To investigate the drug-resistant genes at hepatitis B virus （HBV） polymerase region during entecavir （ETV） treatment. Methods Serum samples from chronic hepatitis B patients with viro- logic breakthrough during enticavir therapy were studied. The resistant mutation patterns in the polymerase gene of hepatitis B virus were analyzed using the polymerase chain reaction （PCR） -sequencing method. Results ETV resistance was detected from 19 out of 29 ETV-refractory patients, among whom 16 （84.2%） had a hisotry of lamivudine-refraetory. The mutation patterns were diverse, while rtL180 ＋ rtM204 ＋ rtT184 （58.6% , 17/29） was most common in patients with ETV genotype resistance. Four of 7 patients （7/29, 24. 1% ） with genotype B were detected to have ETV genotype resistance, while 15 of 22 patients （22/29, 75.9% ） with genotype C were detected to have ETV genotype resistance. The rate of ETV genotype resistance was 57. 1% （4/7） and 68.2% （15/22） in patients with genotype B and genotype C, while no statistical difference was found （P = 0. 665 ） . Conclusions ETV genotype resistance is more common in patients who have been refractory to ETV and lamivudine sequential treatment, rtM204 ＋ rtL180 ＋ rtT184 mutation is common in genotype B and C ETV re-sistance patients.