Shuang Wu, Tatsuo Kanda, Shingo Nakamoto, Osamu Yokosuka, Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8677, Japan.
World J Gastroenterol. 2013 Dec 21;19(47):8940-8. doi: 10.3748/wjg.v19.i47.8940.
Direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection are one of the major advances in its medical treatment. The HCV protease inhibitors boceprevir and telaprevir were the first approved DAAs in the United States, Europe, and Japan. When combined with peginterferon plus ribavirin, these agents increase sustained virologic response rates to 70%-80% in treatment-naïve patients and previous-treatment relapsers with chronic HCV genotype 1 infection. Without peginterferon plus ribavirin, DAA mono-therapies increased DAA-resistance mutations. Several new DAAs for HCV are now in clinical development and are likely to be approved in the near future. However, it has been reported that the use of these drugs also led to the emergence of DAA-resistance mutations in certain cases. Furthermore, these mutations exhibit cross-resistance to multiple drugs. The prevalence of DAA-resistance mutations in HCV-infected patients who were not treated with DAAs is unknown, and it is as yet uncertain whether such variants are sensitive to DAAs. We performed a population sequence analysis to assess the frequency of such variants in the sera of HCV genotype 1-infected patients not treated with HCV protease inhibitors. Here, we reviewed the literature on resistance variants of HCV protease inhibitors in treatment naïve patients with chronic HCV genotype 1, as well as our experience.
直接作用抗病毒药物（DAAs）治疗丙型肝炎病毒（HCV）感染是其医学治疗的主要进展之一。HCV 蛋白酶抑制剂博赛泼维与特拉泼维是美国、欧洲和日本首先批准的 DAAs。与聚乙二醇干扰素加利巴韦林联合使用时，这些药物可将初治患者和慢性 HCV 基因 1 型感染既往治疗复发患者的持续病毒学应答率提高到 70%-80%。不联合聚乙二醇干扰素加利巴韦林时，DAA 单药治疗会增加 DAA 耐药突变。目前正在开发几种新的 HCV DAA，预计在不久的将来会获得批准。然而，据报道，这些药物的使用也导致某些情况下出现 DAA 耐药突变。此外，这些突变对多种药物表现出交叉耐药性。未接受 DAA 治疗的 HCV 感染患者中 DAA 耐药突变的流行情况尚不清楚，也不确定这些变异是否对 DAA 敏感。我们进行了一项群体序列分析，以评估未接受 HCV 蛋白酶抑制剂治疗的 HCV 基因 1 型感染患者血清中存在此类变异的频率。在此，我们回顾了关于初治慢性 HCV 基因 1 型患者 HCV 蛋白酶抑制剂耐药变异的文献，并介绍了我们的经验。
