替比夫定治疗慢性乙型肝炎患者52周HBV耐药分析  

Analysis of the genotypic resistance of HBV in patients with chronic hepatitis B infection treated with telbivudine for 52 weeks

作　　者：高淑春[1] 崔蕾[1] 耿大影[1] 张立新[1] 陈士俊[1] 

机构地区：[1]山东大学附属济南市传染病医院,山东济南250021

出　　处：《中国病原生物学杂志》2012年第10期774-777,共4页Journal of Pathogen Biology

摘　　要：目的研究替比夫定(LdT)治疗基因C型慢性乙型肝炎(CHB)病人52周HBV耐药情况及变异位点。方法初治的基因C型CHB 40例(治疗前应用核酸扩增荧光定量及测序法进行耐药突变检测,HBV-P区均未测到耐药变异),给予LdT 600mg qd治疗52周。病人在治疗前及治疗后每3个月均做肝功、HBV血清学指标、HBV DNA定量检测(COBAS?TaqMan?,最低检测限300copies/ml)。选择LdT治疗52周HBV DNA>1 000copies/ml者,对其36周及52周血清再次进行HBV-P区耐药突变检测。结果 21例(52.5%)病人HBV DNA<300copies/ml,16例(40.0%)HBV DNA>1 000copies/ml,3例(7.5%)HBeAg阳性病人发生HBeAg血清学转换。10例(25.0%)52周检测到HBV-P区耐药突变,其中2例rtA181T变异,7例rtM204I变异,1例rtM204I+L180M变异。结论初治CHB病人,尤其是基线HBV DNA定量较高者,对LdT治疗有较高的耐药率,HBV基因可发生1个或多个位点耐药变异,rtM204I是LdT耐药的主要突变位点。Objective The aim of this study was to determine the incidence of genotypic resistance（GR） and analyze the amino acid substitutions associated with telbivudine（LdT） resistance in week 52 in patients with genotype C hepatitis B who were treated with LdT.Methods Subjects were 40 nucleos（t）ide analogue（NA）-naive patients with genotype C chronic hepatitis B（CHB）.All patients without GR received LdT 600 mg once a day for 52 weeks.ALT levels and the quantity of hepatitis B surface antigen（HBsAg）,HBeAg,and HBV DNA（COBAS TaqMan,lower limit of detection 300 copies/ml）were determined and analyzed at the baseline and at three-month intervals during therapy.Genotypic resistance was examined in weeks 36 and 52 by direct sequencing in patients with HBV DNA 1 000 copies/ml in week 52.Results Forty patients finished the 52-week treatment.At the end of the study,HBV DNA was not detected（HBV DNA 300 copies/ml） in 21 patients（52.5%）and HBV DNA 1 000 copies/ml in 16（40.0%）.HBeAg seroconversion was achieved in three patients（7.5%）.Ten patients（25%）developed drug resistance.Of these,two had the rtA181T mutation,seven had the rtM204I mutation,and 1 had the rtM204I and rtL180M mutations.Conclusion NA-naive patients with CHB treated with LdT were more likely to develop GR.This was particularly true for patients with higher HBV DNA levels at the baseline.GR to LdT involved one or more mutations,the most prevalent of which was the rtM204I mutation.

关 键 词：肝炎病毒 乙型 耐药分析 变异 替比夫定 

分 类 号：R512.62[医药卫生—内科学]