Detection of lamivudine- or adefovir-resistant hepatitis B virus mutations by a liquid array

Detection of lamivudine- or adefovir-resistant hepatitis B virus mutations by a liquid array
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通过液体阵列检测拉米夫定或阿德福韦耐药的乙型肝炎病毒突变

DOI:
10.1016/j.jviromet.2011.04.005
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发表时间:
2011-07-01
影响因子:
3.1
通讯作者:
Zhang, Jiming
Zhang, Jiming
中科院分区:
医学4区
文献类型:
--
作者:
Liu, Hongyan;Mao, Richeng;Zhang, Jiming

文献摘要

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建立了一种新的聚合酶链式反应-Luminex方法,用于快速、准确和高通量地检测最重要的乙肝病毒变异,包括逆转录酶结构域L180M、M204I/V、A181T/V/S、I233V和N2361变异与拉米夫定(LAM)或阿德福韦(ADV)耐药相关的变异。使用突变株和野生型的混合病毒,该方法对103个HBVM1(-1)的检测具有足够的敏感性,当它们占总病毒总数的5%时,可以检测到轻微的突变。将两种方法检测患者临床耐LAM或ADV慢性乙肝病毒感染的结果进行比较,结果显示:两种方法检测LAM或ADV耐药变异的符合率分别为97.9%(48/49)和93.3%(14/15)。与直接测序的符合率为70.3%,与的符合率为45%。聚合酶链式反应-Luminex试验或多分析物悬浮阵列可以同时有效地在许多临床样本中检测感染早期的少数群体乙肝病毒变异。它是一种简单、经济有效的方法,用于耐药性监测或选择合适的抗病毒药物,并在出现耐药相关病毒或生化突破之前及时启动救援治疗。(C)2011爱思唯尔B.V.保留所有权利。
A novel polymerase chain reaction (PCR)-Luminex assay was developed for rapid, accurate, and high-throughput detection of the most important hepatitis B virus (HBV) variants, including those with reverse transcriptase (RI) domain L180M, M204I/V, A181T/V/S, I233V and N2361 mutations associated with resistance to lamivudine (LAM) or adefovir (ADV). Using mixtures of mutant and wild-type HBV, this method was sufficiently sensitive for detecting 103 HBV m1(-1) and could detect minor mutants when they comprised 5% of the total viral population. Comparison of the PCR-Luminex assay with INNO-LiPA for detecting clinical LAM- or ADV-resistant chronic hepatitis B virus infection in 64 patients confirmed the following: the 2 methods were 97.9% (48 of 49) and 93.3% (14 of 15) concordant for detecting LAM- or ADV-resistance mutations, respectively. The agreement with direct sequencing was 70.3% (45 of 64). The PCR-Luminex assay or multi-analyte suspension array can detect simultaneously and efficiently minor populations HBV mutants early during infection in many clinical samples. It is a simple, cost-effective method for resistance surveillance or selecting appropriate antiviral agents and initiating timely rescue treatment before the development drug-resistance related virus or biochemical breakthrough. (C) 2011 Elsevier B.V. All rights reserved.