乙型肝炎患者P基因变异位点的检测及阿德福韦疗效的观察  

Study on the detection of hepatitis B virus polymerase gene variations and therapeutic effects of adefovir dipivoxil in patients with chronic hepatitis B

作　　者：方文佳[1] 盛吉芳[2] 黄海军[2] 匡逄春[3] 

机构地区：[1]浙江省立同德医院感染科,杭州310012 [2]浙江大学医学院附属第一医院感染科 [3]湖南农业大学湖南省植物激素重点实验室

出　　处：《中华传染病杂志》2008年第2期92-96,共5页Chinese Journal of Infectious Diseases

摘　　要：目的探讨P基因突变发生频率、类型、位点及其与耐药的相互关系，观察阿德福韦的临床疗效。方法PCR扩增和纯化HBV DNA P基因，Mega BACETM500测序，软件分析结果。慢性乙型肝炎患者60例，拉米夫定治疗半年以上并符合临床耐药标准。YMDD变异者采用阿德福韦10mg／d口服，观察治疗前后临床指标的变化。数据行t检验和Х^2检验。结果拉米夫定耐药患者P基因YMDD变异率高达80％，变异位点为P基因C区204位点和B区180位点，变异类型为rtL180M／M204V、rtM204I、rtL180M／M204I，单独变异与联合变异并存；阿德福韦对HBV YMDD变异株有显著抑制作用，HBV DNA由治疗前的（7．26±1．26）log10拷贝／mL降为治疗24周后的（4．05±0．79）log10拷贝／mL，24周ALT复常率为87．5％，HBeAg阴转率达20．8％，抗-HBe阳转率为8．3％（P值均〈0．05）。阿德福韦治疗后血尿常规、肾功能、电解质（包括血磷）、甲胎蛋白等均未出现异常，具有良好的安全性。结论拉米夫定耐药既存在不同类型YMDD变异，也存在不同位点的变异。阿德福韦对有YMDD变异的乙型肝炎患者有一定疗效。Objective To investigate the mutation frequency, type and sites of P gene and their correlations with drug resistance as well as the therapeutic effects of adefovir dipivoxil （ADV） on patients with chronic hepatitis B （CHB）. Methods HBV DNA P gene was amplified by polymerase chain reaction （PCR）. The PCR products were purified and sequenced using Mega BACETM 500 sequenator. The sequencing data were analyzed by sequencing software. Sixty patients with CHB were recruited, who were treated with lamivudine for at least half year and clinically resistant to lamivudine. The patients who developed YMDD mutation were switched to ADV 10 nag daily and the clinical data before and after switch were collected. Results The mutation frequency of YMDD of HBV polymerase gene was up to 80 % in patients with lamivudine resistance and the mutation sites were located ,in C204 and B180. The mutation types were rtL180M/M204V, rtM204I and rtL180M/M204L Single mutation and multi-mutation were found at the same time. ADV could significantly suppress the replication of HBV YMDD mutant strain. HBV DNA level decreased from （7.26 ± 1.26）log10copy/mL before switch to （4.05 ± 0. 79）log10 copy/mL after switch to ADV for 24 weeks. Alanine aminotransferase normalization rate, HBeAg negative rate and HBeAb positive rate were 87.5% , 20. 8% and 8.3% at week 24, respectively （all P 〈 0. 05）. No adverse events were found by detecting blood routine, urine routine, renal function, electrolytes （including blood phosphorus）, fibrosis index and aipha-fetoprotein after treated with ADV. Conclusions There are not only different types of YMDD mutation, but also different sites of iamivudine resistance. ADV is effective on CHB patients with YMDD mutation.

关 键 词：肝炎病毒 乙型 拉米夫定 阿德福韦 DNA 病毒 变异(遗传学) 基因 病毒 

分 类 号：R512.62[医药卫生—内科学] R373.1[医药卫生—临床医学]