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首页> 外文期刊>Journal of Clinical Microbiology >Ultradeep Pyrosequencing of NS3 To Predict Response to Triple Therapy with Protease Inhibitors in Previously Treated Chronic Hepatitis C Patients
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Ultradeep Pyrosequencing of NS3 To Predict Response to Triple Therapy with Protease Inhibitors in Previously Treated Chronic Hepatitis C Patients

机译:NS3的超深焦测序技术可预测先前治疗的慢性丙型肝炎患者对蛋白酶抑制剂三联疗法的反应

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Despite the gain in sustained virological responses (SVR) provided by protease inhibitors (PIs), failures still occur. The aim of this study was to determine if a baseline analysis of the NS3 region using ultradeep pyrosequencing (UDPS) can help to predict an SVR. Serum samples from 40 patients with previously nonresponding genotype 1 chronic hepatitis C who were retreated with triple therapy, including a PI, were analyzed. Baseline UDPS of the NS3 gene was performed on plasma and peripheral blood mononuclear cells (PBMC). Mutations conferring resistance to PIs were sought. The overall diversity of the quasispecies was evaluated by calculating the Shannon entropy (SE). Resistance mutations were found in plasma and PBMC but were not discriminating enough to predict an SVR. NS3 quasispecies heterogeneity was significantly lower at baseline in patients achieving an SVR than in those not achieving an SVR (SE of 26.98 ± 16.64 × 10?3 versus 44.93 ± 19.58 × 10?3, P = 0.0047). With multivariate analysis, the independent predictors of an SVR were fibrosis of stage F ≤2 (odds ratio [OR], 13.3; 95% confidence interval [CI], 1.25 to 141.096; P < 0.03) and SE below the median (OR, 5.4; 95% CI, 1.22 to 23.87; P < 0.03). More than the presence of minor mutations at the baseline in plasma or in PBMC, the NS3 viral heterogeneity determined by UDPS is an independent factor for an SVR in previously treated patients receiving triple therapy that includes a PI.
机译:尽管蛋白酶抑制剂(PIs)提供的持续病毒学应答(SVR)有所增加,但故障仍然会发生。这项研究的目的是确定使用超深焦磷酸测序(UDPS)对NS3区域进行基线分析是否可以帮助预测SVR。分析了来自40位先前无反应的1型慢性C型慢性丙型肝炎患者的血清样品,这些患者接受了包括PI在内的三联疗法的复治。 NS3基因的基线UDPS在血浆和外周血单核细胞(PBMC)上进行。寻找赋予对PI的抗性的突变。通过计算香农熵(SE)评估了准种的总体多样性。在血浆和PBMC中发现了抗药性突变,但不能充分区分以预测SVR。获得SVR的患者在基线时NS3准种异质性显着低于未获得SVR的患者(SE为26.98±16.64×10 ?3 与44.93±19.58×10 ?3 P = 0.0047)。通过多变量分析,SVR的独立预测因素是F≤2期纤维化(几率[OR]为13.3; 95%置信区间[CI]为1.25至141.096; P <0.03)和SE低于中位数(OR,5.4; 95%CI,1.22至23.87; P <0.03)。由UDPS确定的NS3病毒异质性不仅是血浆或PBMC基线中微小突变的存在,而且是接受三联疗法(包括PI)的先前治疗患者中SVR的独立因素。

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