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The Role of Hepatitis C Virus Core Antigen Testing in the Era of Direct Acting Antiviral Therapies: What We Can Learn from the Protease Inhibitors

机译:丙型肝炎病毒核心抗原检测在直接作用抗病毒治疗时代中的作用:我们可以从蛋白酶抑制剂中学到什么

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摘要

Direct-acting antiviral (DAA) therapies have revolutionised the treatment of hepatitis C virus (HCV). The financial cost of DAAs however is significant, and first generation protease inhibitors (PIs) also require frequent monitoring of viral RNA levels to guide treatment. In this context, we examined the relevance of HCV antigen testing to evaluate the potential role in monitoring virological response to HCV antiviral treatment with the PI-based triple therapies, telaprevir (TVR) and boceprevir (BOC). Chronic HCV-infected individuals (n = 152) enrolled in the Irish Hepatitis C Outcomes Research Network (ICORN) study were prospectively analysed for baseline markers and the early viral kinetics associated with SVR. The sustained virological response (SVR) rates in the cohort receiving TVR and BOC were 87.3% and 73.8%, respectively. Baseline factors associated with successful outcome in TVR therapy were age (P = 0.0098), IFNL3 genotype (P = 0.0330) and viral load (P = 0.0456). RNA level at week 4 (P = 0.0068) and viral antigen negativity at week 2 (P = 0.0359) were predictive of SVR for TVR-based therapy. In BOC therapy, prior interferon treatment (P = 0.0209) and IFNL3 genotype (P = 0.0410) were baseline predictors of SVR. Evidence of viraemia based either on viral RNA or antigen at week 4 predicted SVR in these patients. Our data showed that rapid decline of HCV antigen to negative level at week 2 in TVR treatment and <0.96 log fmol/l in BOC treatment after commencement of PI triple therapy were associated with SVR. HCV antigen measurement should be considered as a potential alternative for monitoring treatment response during DAA-based regimens.
机译:直接作用抗病毒(DAA)疗法彻底改变了丙型肝炎病毒(HCV)的治疗方法。但是,DAA的财务成本很高,并且第一代蛋白酶抑制剂(PIs)还需要经常监测病毒RNA水平以指导治疗。在这种情况下,我们检查了HCV抗原检测的相关性,以评估在基于PI的三联疗法telaprevir(TVR)和boceprevir(BOC)监测HCV抗病毒治疗的病毒学应答中的潜在作用。前瞻性分析了参加爱尔兰丙型肝炎结果研究网络(ICORN)研究的慢性HCV感染者(n = 152)的基线标志物以及与SVR相关的早期病毒动力学。接受TVR和BOC的人群的持续病毒学应答(SVR)率分别为87.3%和73.8%。与TVR治疗成功相关的基线因素是年龄(P = 0.0098),IFNL3基因型(P = 0.0330)和病毒载量(P = 0.0456)。第4周时的RNA水平(P = 0.0068)和第2周时的病毒抗原阴性(P = 0.0359)可以预测基于TVR疗法的SVR。在BOC治疗中,先前的干扰素治疗(P = 0.0209)和IFNL3基因型(P = 0.0410)是SVR的基线预测指标。在第4周时基于病毒RNA或抗原的病毒血症的证据预测了这些患者的SVR。我们的数据显示,在开始三联PI治疗后,TVR治疗第2周HCV抗原迅速下降至阴性水平,BOC治疗后HCV抗原<0.96 log fmol / l与SVR相关。 HCV抗原测量应被视为在基于DAA的方案中监测治疗反应的潜在替代方法。

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