Characterization of naturally occurring protease inhibitor-resistance mutations in genotype 1b hepatitis C virus patients
Characterization of naturally occurring protease inhibitor-resistance mutations in genotype 1b hepatitis C virus patients
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DOI：
10.1007/s12072-011-9306-7
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发表时间：
2012-04-01
影响因子：
6.6
通讯作者：
Enomoto, Nobuyuki
中科院分区：
文献类型：
--
作者：
Shindo, Hiroko;Maekawa, Shinya;Enomoto, Nobuyuki
背景与目的根据最近的报道，丙型肝炎病毒(丙型肝炎病毒)耐药变异株可能大量存在于未治疗丙型肝炎病毒的患者中。方法对261例日本丙型肝炎患者在接受聚乙二醇化干扰素联合利巴韦林治疗前，对261例日本丙型肝炎患者进行丙型肝炎病毒非结构蛋白3(NS3)优势氨基酸序列测定，分析患者的临床特征和持续病毒学应答(SVR)率。结果261例患者中有35例(13.4%)存在4个已知的PI耐药单突变(T54S、Q80K、I153V和D168E)，6例(2.3%)存在双突变(I153V+T54S/D168E)。有无PI耐药突变的患者对聚乙二醇干扰素/RBV治疗的反应无差异(突变组，SVR为48%；野生型组，SVR为40%；P=0.38)。另一方面，两例非SVR患者在接受聚乙二醇-干扰素/RBV治疗后出现两种突变(I153V和E168D，5.1%)。结论在未经治疗的丙型肝炎病毒感染患者中，存在相当比例的PI耐药相关NS3突变。这些突变在PI治疗中的影响尚不清楚，但临床医生应注意避免PI耐药性的进一步发展。
Background and aims Protease inhibitor (PI)-resistant hepatitis C virus (HCV) variants may be present in substantial numbers in PI-untreated patients according to recent reports. However, influence of these viruses in the clinical course of chronic hepatitis C has not been well characterized.Methods The dominant HCV nonstructural 3 (NS3) amino acid sequences were determined in 261 HCV genotype 1b-infected Japanese patients before pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, and investigated the patients' clinical characteristics as well as treatment responses including sustained virological response (SVR) rate. HCV-NS3 sequences were also determined in 39 non-SVR patients after completion of the therapy.Results Four single mutations (T54S, Q80K, I153V, and D168E) known to confer PI resistance were found in 35 of 261 patients (13.4%), and double mutations (I153V plus T54S/D168E) were found in 6 patients (2.3%). Responses to PEG-IFN/RBV therapy did not differ between patients with and without PI-resistance mutations (mutation group, SVR 48%; wild-type group, SVR 40%; P = 0.38). On the other hand, two mutations appeared in two non-SVR patients after PEG-IFN/RBV therapy (I153V and E168D, 5.1%).Conclusions PI-resistance-associated NS3 mutations exist in a substantial proportion of untreated HCV-1b-infected patients. The impact of these mutations in the treatment of PIs is unclear, but clinicians should pay attention to avoid further development of PI resistance.