Kan Toshiki, Hashimoto Senju, Kawabe Naoto, Murao Michihito, Nakano Takuji, Shimazaki Hiroaki, Nakaoka Kazunori, Ohki Masashi, Takagawa Yuka, Kurashita Takamitsu, Takamura Tomoki, Yoshioka Kentaro
Department of Liver, Biliary Tract and Pancreas Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukakecho, Toyoake, Aichi, 470-1192, Japan.
J Gastroenterol. 2016 Jan;51(1):63-70. doi: 10.1007/s00535-015-1080-1. Epub 2015 Apr 24.
Resistance-associated variants (RAVs) reduce the efficacy of interferon (IFN)-free therapy with asunaprevir and daclatasvir for patients infected with hepatitis C virus (HCV) genotype 1b. The characteristics of patients with an L31 or a Y93 variant in the nonstructural 5A region detected by a polymerase chain reaction invader assay were investigated.
In total, 201 patients with HCV genotype 1b were examined for L31F/M/V variants or a Y93H variant by the polymerase chain reaction invader assay.
L31M and Y93H variants were detected in 4.6 and 21.4 % of patients, respectively. Patients with an L31M variant had no significant characteristics. Patients with a Y93H variant had significantly higher HCV RNA levels (6.5 ± 0.5 log copies per milliliter vs 6.1 ± 0.7 log copies per milliliter, p = 0.0002), higher frequency of mutant type of the IFN-sensitivity-determining region (88.4 % vs 71.7 %, p = 0.0251), and higher frequency of TT genotype at rs8099917 of IL28B (91.7 % vs 54.3 %, p < 0.0001) than those with Y93 wild-type strains. Multivariate analysis identified HCV RNA levels [odds ratio (OR) 3.72, 95 % confidence interval (CI) 1.71-8.06, p = 0.0009] and TT genotype at rs8099917 (OR 7.45, 95 % CI 2.11-26.4, p = 0.0018) as factors associated with the presence of a Y93H variant.
The presence of a Y93H variant was associated with higher HCV RNA levels and TT genotype at rs8099917 of IL28B. Thus, patients with a Y93H variant may be ideal candidates for IFN-based therapy rather than IFN-free therapy, although the high viral load of these patients may reduce the response rate of IFN-based therapy.
耐药相关变异（RAVs）会降低丙型肝炎病毒（HCV）1b型感染患者使用asunaprevir和daclatasvir进行无干扰素治疗的疗效。研究了通过聚合酶链反应侵入检测法在非结构5A区域检测到L31或Y93变异的患者的特征。
总共对201例HCV 1b型患者通过聚合酶链反应侵入检测法检测L31F/M/V变异或Y93H变异。
分别在4.6%和21.4%的患者中检测到L31M和Y93H变异。L31M变异的患者没有显著特征。Y93H变异的患者HCV RNA水平显著更高（6.5±0.5 log拷贝/毫升 vs 6.1±0.7 log拷贝/毫升，p = 0.0002），干扰素敏感性决定区域突变型的频率更高（88.4% vs 71.7%，p = 0.0251），以及IL28B的rs8099917处TT基因型的频率更高（91.7% vs 54.3%，p < 0.0001），高于Y93野生型菌株的患者。多因素分析确定HCV RNA水平[比值比（OR）3.72，95%置信区间（CI）1.71 - 8.06，p = 0.0009]和rs8099917处的TT基因型（OR 7.45，95% CI 2.11 - 26.4，p = 0.0018）为与Y93H变异存在相关的因素。
Y93H变异的存在与更高的HCV RNA水平以及IL28B的rs8099917处的TT基因型相关。因此，Y93H变异的患者可能是基于干扰素治疗而非无干扰素治疗的理想候选者，尽管这些患者的高病毒载量可能会降低基于干扰素治疗的反应率。
