海岛地区NA治疗无良好应答CHB患者HBV P区耐药突变分析  

Analysis on drug resistance mutation of HBV P region in CHB patients without good response to NA treatment in island area

作　　者：何剑营[1] 周吉航[1] 竺王玉[1] 陈冬冬[1] 黄燕燕[1] 李世波[2] 

机构地区：[1]浙江省舟山医院细胞分子生物学实验室,舟山316021 [2]浙江省舟山医院感染科,舟山316021

出　　处：《现代医药卫生》2015年第16期2409-2411,共3页Journal of Modern Medicine & Health

基　　金：浙江省科技厅项目(2011C37030;2013C37079;2011C33089)

摘　　要：目的分析舟山地区经核苷类似物(NA)治疗无良好应答的慢性乙型肝炎(CHB)患者乙型肝炎病毒(HBV)P区耐药突变模式。方法收集2011年10月至2013年11月188例于浙江省舟山医院接受NA治疗无良好应答的CHB患者血清,采用直接测序法检测患者HBV P区基因突变状态。结果 188例经NA治疗无良好应答的CHB患者HBV P区基因突变率为71.28%(134/188),主要模式:rt L180M+rt M204V/I/S突变率为26.12%(35/134),rt M204V/I/S突变率为25.37%(34/134),rt M181T/V/S突变率为16.42%(22/134);其中113例服用单种NA无良好应答患者有73例发生耐药变异(73/113,64.60%),多位点(3个及以上耐药位点)突变率为12.33%(9/73);75例服用多种NAs无良好应答患者有61例发生变异(61/75,81.33%),多位点突变率为16.39%(10/61),多药使用者发生耐药突变率明显高于单药使用者,差异有统计学意义(χ2=6.631,P<0.05)。结论在NA治疗无良好应答CHB患者中耐药变异发生率高,且长期服用多种NAs易发生多点突变;监测HBV P区耐药突变可为NA耐药CHB患者用药提供依据。Objective To analyze the drug resistance mutation patterns of the HBV P region in CHB patients without good response to the nucleoside analogues（NA） treatment in Zhoushan area. Methods Sera were collected from the chronic hepatitis B（CHB） patients without good response to the NA treatment in our hospital from October 2011 to November 2013 and de tected the gene mutation status of the HBV P region by using the direct sequencing method. Results In 188 CHB patients without good response to the NA treatment,the gene mutation rate of HBV P region was 71.28%（134/188）,the main patterns included rt L180M＋rt M204V/I/S in 35 cases（35/134,26.12%）,rt M204V/I/S in 34 cases（34/134,25.37%） and rt M181T/V/S in 22 cases（22/134,16.42%）;among 113 CHB patients without good response to single NA treatment,73 cases（73/113,64.60%） developed the drug resistance mutation,the incidence rate of multi-site（three or more sites） mutations was 12.33%（9/73）;in 75 cases of multiple NAs without good response,61 cases（61/75,81.33%） developed the variation,the multiple site mutation rate was 16.39%（10/61）,the drug resistance rate in the cases of multiple NAs was significantly higher than that in the cases of single NA,the differences was statistically sig nificant（χ2=6.631,P0.05）. Conclusion The CHB patients without good response to the NA treatment have higher drug resistance mutation rate,moreover long term taking multiple NAs is easy to generate the multi-site drug resistance mutation;monitoring the drug resistance mutation of HBV P region can provide the basis for the medication in the patients with NA-resistant CHB patients.

关 键 词：肝炎病毒 乙型 肝炎 乙型 慢性 核苷类 DNA突变分析 药物耐受性 

分 类 号：R373.1[医药卫生—病原生物学]