Ronsin Christophe, Pillet Anne, Bali Corinne, Denoyel Gérard-Antoine
Laboratoire L.C.L., Service de Biologie Moléculaire, 78 Avenue de Verdun, BP 110, 94208 Ivry sur Seine, France.
J Clin Microbiol. 2006 Apr;44(4):1390-9. doi: 10.1128/JCM.44.4.1390-1399.2006.
Quantitative detection of hepatitis B virus (HBV) in serum or plasma has become the most direct and reliable method for monitoring chronic hepatitis B. Here, we report the performance characteristics of a real-time PCR hepatitis B DNA quantitative assay, the COBAS TaqMan (CTM) HBV test (Roche Diagnostics, Meylan, France), in combination with an automated DNA extraction on the COBAS AmpliPrep (CAP) instrument using the total nucleic acid isolation kit (TNAI kit), a generic reagent for nucleic acid isolation (both from Roche Diagnostics). The linearity, accuracy, and specificity of the CAP-TNAI-CTM HBV test were evaluated using various reference panels and standards (HBV panel 2004 from Quality Control for Molecular Diagnostics, OptiQuant HBV panel from AcroMetrix, WHO International Standard for HBV, and Teragenix hepatitis B genotype panel). Quantitative results show that the CAP-TNAI-CTM HBV test performed well with respect to linearity, accuracy, and reproducibility from at least 100 to 500,000 HBV DNA IU/ml. Based on the log(10) IU of HBV DNA/ml measured, the intra-assay variation ranged from 2.49% to 8.46% and the interassay variation ranged from 1.88% to 7.83%. The test was extremely sensitive and could detect samples containing HBV DNA below the reported quantification threshold (<30 IU/ml). All HBV genotypes were correctly amplified, and no cross-contamination occurred during the automated sample preparation. In addition, 402 human serum samples were tested comparatively to the VERSANT HBV DNA 3.0 assay (bDNA; Bayer Diagnostics, Puteaux, France). The viral load results of the CAP-TNAI-CTM test and bDNA were significantly correlated, but the agreement between the two tests was poor, with large differences between results for individual samples. The hands-on time was estimated to be reduced from 2.30 h with bDNA to 45 min with the CAP-TNAI-CTM test, and up to 84 samples were completely processed within a working day. Overall, the performance characteristics of the CAP-TNAI-CTM test demonstrated that it provides a high-throughput sensitive and reliable method for quantitation of HBV DNA levels in the routine molecular laboratory.
血清或血浆中乙型肝炎病毒(HBV)的定量检测已成为监测慢性乙型肝炎最直接、可靠的方法。在此,我们报告一种实时荧光定量聚合酶链反应(PCR)检测HBV DNA定量分析方法,即COBAS TaqMan(CTM)HBV检测法(罗氏诊断公司,法国梅兰),联合使用总核酸分离试剂盒(TNAI试剂盒)在COBAS AmpliPrep(CAP)仪器上进行自动DNA提取,TNAI试剂盒是一种通用的核酸分离试剂(均来自罗氏诊断公司)。使用各种参考品和标准品(分子诊断质量控制的HBV参考品2004、AcroMetrix公司的OptiQuant HBV参考品、世界卫生组织HBV国际标准品以及Teragenix乙型肝炎基因分型参考品)评估CAP-TNAI-CTM HBV检测法的线性、准确性和特异性。定量结果显示,CAP-TNAI-CTM HBV检测法在至少100至500,000 HBV DNA国际单位/毫升范围内,线性、准确性和重复性良好。基于测得的每毫升HBV DNA的对数(10)国际单位,批内变异范围为2.49%至8.46%,批间变异范围为1.88%至7.83%。该检测法极其灵敏,能够检测出HBV DNA含量低于报告定量阈值(<30国际单位/毫升)的样本。所有HBV基因型均能正确扩增,在自动样本制备过程中未发生交叉污染。此外,对402份人血清样本与VERSANT HBV DNA 3.0检测法(分支DNA检测法;拜耳诊断公司,法国皮托)进行了比较检测。CAP-TNAI-CTM检测法和分支DNA检测法的病毒载量结果显著相关,但两种检测法的一致性较差,个别样本的结果差异较大。据估计,手工操作时间从使用分支DNA检测法的2.30小时减少至使用CAP-TNAI-CTM检测法的45分钟,且在一个工作日内最多可完全处理84个样本。总体而言,CAP-TNAI-CTM检测法的性能特点表明,它为常规分子实验室中HBV DNA水平的定量提供了一种高通量、灵敏且可靠的方法。