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Predictors of Response to 24-Week Telaprevir-Based Triple Therapy for Treatment-Naïve Genotype 1b Chronic Hepatitis C Patients

机译:预测治疗初治基因型1b慢性丙型肝炎患者对基于24周特拉帕韦韦的三联疗法的反应

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摘要

We evaluated the genetic variation in rs8099917, substitutions in core amino acid (aa) 70, and the number of aa substitutions in the interferon sensitivity-determining region (ISDR) on the prediction of sustained virological response (SVR) in treatment-naïve hepatitis C virus (HCV) genotype 1b (G1b) patients. This multicenter study involved 150 Asian treatment-naïve patients infected with HCV G1b who received 12 weeks of telaprevir in combination with 24 weeks of peginterferon-α-2b and ribavirin. The baseline and treatment-related factors potentially associated with SVR were determined by multivariate logistic regression analysis. Virological response was analyzed on an intent-to-treat basis. Cessation of the therapy due to adverse effects occurred in only 2 patients, who discontinued the trial at 10 weeks and at 2 weeks due to cerebral infarction and renal impairment, respectively. Among the 150 patients in whom the final virological response was determined, only genotype TT in rs8099917 was identified as a pretreatment predictor (P = 7.38 × 10−4). Achievement of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 of treatment, was identified as an after-starting-treatment predictor (P = 2.47 × 10−5). However, neither a substitution in core aa 70 nor the number of substitutions in the ISDR affected treatment outcome.
机译:我们评估了rs8099917的遗传变异,核心氨基酸(aa)70的取代以及干扰素敏感度决定区域(ISDR)中aa取代的数目,以预测未经治疗的丙型肝炎的持续病毒学应答(SVR)病毒(HCV)基因型1b(G1b)患者。这项多中心研究涉及150名接受HCV G1b治疗的亚洲初治患者,他们接受了12周的telaprevir联合24周的聚乙二醇干扰素-α-2b和利巴韦林治疗。通过多因素Logistic回归分析确定了可能与SVR相关的基线和治疗相关因素。在意向性治疗的基础上分析了病毒学应答。只有2名患者因不良反应而中止治疗,分别由于脑梗塞和肾功能不全而在10周和2周时中止了试验。在确定最终病毒学应答的150例患者中,只有rs8099917中的基因型TT被确定为治疗前的预测因子(P = 7.38×10 −4 )。快速病毒学应答(RVR)的定义为在治疗的第4周无法检测到HCV RNA,被确定为治疗后的预后指标(P = 2.47×10 -5 )。但是,核心氨基酸70的取代和ISDR的取代数量均不会影响治疗效果。

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