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目的探讨未经核苷(酸)类似物治疗的乙型肝炎病毒(HBV)感染者HBV P基因逆转录(RT)区准种异质性及预存耐药情况,为临床抗病毒治疗药物选择提供理论依据。方法 2011年10月至2013年4月期间于中国医科大学附属盛京医院感染科住院的60例慢性HBV感染者为研究对象。检测HBV P RT区准种异质性及预存耐药情况;乙型肝炎病毒血清学标志物检测采用化学发光法;乙型肝炎病毒载量测定采用Tag Man实时荧光定量PCR法。HBV P RT准种异质性及预存耐药检测应用克隆测序法。结果 60例患者中32例(53.3%)检测出RT区基因变异,其中乙肝病毒携带者组、慢性乙型肝炎组和乙肝肝硬化组之间相比差异无统计学意义(P>0.05)。对HBV RT区的核苷酸序列分析共发现31种变异模式。拉米夫定预存耐药8例(1.33%)、恩替卡韦预存耐药5例(0.83%),阿德福韦酯预存耐药7例(1.16%)。乙肝肝硬化组准种复杂性(38.3%)明显高于慢性乙型肝炎(2.83%)和乙肝病毒携带者(1.33%)。e抗原(HBe Ag)阳性组RT区变异发生率为52.6%,阴性组为54.5%,两组差异无统计学意义。结论 HBV逆转录酶区核苷(酸)预存耐药天然存在,变异模式多种多样。HBV不同感染阶段RT区各耐药位点变异发生率差异无统计学意义,但乙肝肝硬化组准种复杂性明显高于慢性乙型肝炎和乙型肝炎病毒携带者。HBe Ag阳性和阴性HBV感染者RT区基因变异率差异无统计学意义。
Objective To investigate the quasi-heterogeneity and pre-existing drug resistance of HBV P gene reverse transcription (RT) region in patients with hepatitis B virus (HBV) infection without nucleoside (acid) analogue therapy, and to provide clinical anti-viral drug choice Theoretical basis. Methods From October 2011 to April 2013, 60 cases of chronic HBV infection hospitalized in Department of Infectious Diseases, Shengjing Hospital, China Medical University were studied. HBV P RT region quasispecies heterogeneity and pre-existing drug resistance were detected; the detection of hepatitis B virus serological markers by chemiluminescence; hepatitis B viral load determination using Tag Man real-time PCR method. Heterogeneity of HBV P RT Quasispecies and Precursor Resistance Testing Clone Sequencing. Results The gene mutation in RT region was detected in 32 of 60 patients (53.3%). There was no significant difference between HBV carriers, chronic hepatitis B patients and hepatitis B cirrhosis patients (P> 0.05). A total of 31 mutation patterns were found in the nucleotide sequence of HBV RT region. Lamivudine pre-existing drug resistance in 8 cases (1.33%), entecavir pre-stored resistance in 5 cases (0.83%), adefovir dipivoxil pre-existing resistance in 7 cases (1.16%). The quasispecies complexity (38.3%) of patients with hepatitis B cirrhosis was significantly higher than that of patients with chronic hepatitis B (2.83%) and hepatitis B virus carriers (1.33%). The mutation rate of RT in e antigen (HBe Ag) -positive group was 52.6% and in the negative group was 54.5%, there was no significant difference between the two groups. Conclusion Nucleotide (acid) pre-existing drug resistance in HBV reverse transcriptase region exists naturally, with a variety of variation patterns. There was no significant difference in the incidence of variability of drug-resistant loci in RT at different stages of HBV infection, but the quasispecies complexity of hepatitis B cirrhosis group was significantly higher than that of chronic hepatitis B and hepatitis B virus carriers. There was no significant difference in the gene mutation rate of RT in HBeAg-positive and -negative HBV patients.