拉米夫定耐药后联合阿德福韦酯治疗发生再耐药的慢性乙型肝炎患者的基因型及耐药位点分析

杨栋强; 陈芳; 康谊; 丁岗强; 肖二辉; 彭真; 尚佳

doi:10.3969/j.issn.1001-5256.2016.03.016

拉米夫定耐药后联合阿德福韦酯治疗发生再耐药的慢性乙型肝炎患者的基因型及耐药位点分析

DOI: 10.3969/j.issn.1001-5256.2016.03.016

1. 河南省人民医院感染病中心
2. 河南中医药大学

基金项目:

河南省基础与前沿技术研究计划项目(132300410470)；河南省医学科技攻关计划项目(201303144)；

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中图分类号: R512.62
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出版历程
- 出版日期: 2016-03-20

Genotypes and resistance loci in patients with chronic hepatitis B achieving virologic breakthrough in treatment with lamivudine combined with adefovir after developing drug resistance in treatment with lamivudine alone

Center of Infectious Diseases, Henan Provincial People′s Hospital

Research funding:

摘要

摘要: 目的研究拉米夫定（LAM）耐药后联合阿德福韦酯（ADV）抗病毒治疗中发生病毒学突破的慢性乙型肝炎（CHB）患者的耐药位点和基因分型。方法收集2010年6月-2013年6月河南省人民医院收治的89例单用LAM耐药后,联合ADV抗病毒治疗的CHB患者的血清,应用实时定量PCR进行HBV拷贝检测,通过测序进行基因分型,并对rt N236T、rt A181V、rt M204V、rt L180M耐药位点进行检测。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果 89例患者单用LAM治疗后均发生LAM rt M204V位点突变,联合ADV治疗后,9例发生ADV rt N236T单位点突变,5例发生ADV rt A181V单位点突变,8例发生rt A181V+rt N236T双位点联合突变,累计ADV耐药率为24.7%（22/89）。89例患者的HBV基因分型中,C基因型82例,其中8例发生rt A181V+rt N236T双位点联合突变;B基因型7例。结论与B基因型相比,C基因型CHB患者单用LAM耐药后,联合ADV治疗中更易发生rt A181V+rt N236T双位点联合突变。
- 肝炎,乙型,慢性 /
- 拉米夫定 /
- 阿德福韦酯 /
- 基因型 /
- 点突变
Abstract: Objective To investigate the genotypes and resistance loci in patients with chronic hepatitis B( CHB) achieving virologic breakthrough in the treatment with lamivudine( LAM) combined with adefovir( ADV) after developing drug resistance in the treatment with LAM alone. Methods A total of 89 CHB patients who were admitted to Henan Provincial People's Hospital and treated with LAM and ADV as the antiviral therapy after developing drug resistance in the treatment with LAM alone from June 2010 to June 2013 were enrolled,and their serum samples were collected. Quantitative real- time PCR was used for hepatitis B virus( HBV) detection,and sequencing was applied to determine the genotype and detect the resistance loci rt N236 T,rt A181 V,rt M204 V,and rt L180 M. The t- test was applied for comparison of continuous data between groups,and the chi- square test was applied for comparison of categorical data between groups. Results LAM rt M204 V mutation was detected in all the 89 patients after treatment with LAM alone. After the combination therapy with LAM and ADV,ADV rt N236 T mutation was detected in 9 patients,ADV rt A181 V mutation in 5 patients,and rt N236 T + rt A181 V mutation in 8 patients,with an overall ADV resistance rate of 24. 7%( 22 /89). As for HBV genotyping,82 patients had genotype C,and rt A181 V + rt N236 T mutation was detected in 8 patients; 7 patients had genotype B. Conclusion Compared with the patients with HBV genotype B,the patients with genotype C are more susceptible to rt A181 V + rt N236 T mutation during the combination therapy with LAM and ADV after developing drug resistance in the treatment with LAM alone.
- hepatitis B,chronic /
- lamivudine /
- adefovir /
- genotype /
- point mutation

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参考文献(22)

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