Amino acid substitutions in core and NS5A regions of the HCV genome can predict virological decrease with pegylated interferon plus ribavirin therapy
Amino acid substitutions in core and NS5A regions of the HCV genome can predict virological decrease with pegylated interferon plus ribavirin therapy
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DOI：
10.3851/imp1674
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发表时间：
2010-01-01
影响因子：
1.2
通讯作者：
Chayama, Kazuaki
中科院分区：
文献类型：
--
作者：
Kitamura, Shosuke;Tsuge, Masataka;Chayama, Kazuaki
背景：目前治疗慢性丙型肝炎的标准疗法是聚乙二醇化干扰素(PEG化干扰素)加利巴韦林(RBV)联合疗法。最近有报道称，核心区的氨基酸(AA)替换以及干扰素敏感性决定区(ISDR)可以预测非病毒学应答(NVR)、持续病毒学应答(SVR)和早期病毒学应答。尽管这两个预测因素对联合治疗很重要，但它们之间的相互作用尚不清楚。方法：选择117例接受聚乙二醇化干扰素-α2b联合RBV治疗的患者参与本研究。结果：核心区AA序列和γ-谷氨酰转肽酶(GTP)水平与SVR和NVR相关，而ISDR中AA序列与SVR和NVR无关。然而，核心区AA70和AA91位的替换、ISDR中没有替换以及较高水平的γ-GTP是NVR的独立预测因素。核心区AA70和AA91野生型、高血小板计数和低水平的γ-GTP是SVR的独立预测因素。结论：分析核心区和ISDR的AA替换有助于预测联合治疗的疗效，并有助于避免发生SVR的低概率患者暴露于治疗。
Background: The current standard therapy for chronic hepatitis C is pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy. Recently, it has been reported that amino acid (aa) substitutions in the core region, as well as the IFN-sensitivity-determining region (ISDR), were predictive of non-virological response (NVR), sustained virological response (SVR) and early virological response. Despite the importance of these two predictive factors for combination therapy, their interaction is poorly understood.Methods: A total of 117 patients who were treated with PEG-IFN-alpha 2b plus RBV combination therapy were selected for participation in this study. We determined the aa sequences in the core region and ISDR by direct sequencing and analysed them along with clinical data to indentify predictive factors for therapeutic response.Results: The aa sequences in the core region and gamma-glutamyl transpeptidase (GTP) levels were associated with SVR and NVR, but aa sequences in the ISDR were not. However, substitutions at both aa 70 and aa 91 in the core region without substitutions in the ISDR and higher levels of gamma-GTP were independent predictive factors for NVR. Wild-type aa 70 and aa 91 in the core region, higher platelet counts and lower levels of gamma-GTP were independent predictive factors for SVR.Conclusions: These results indicate that analyses of aa substitutions in both the core region and the ISDR are useful for predicting the effectiveness of combination therapy, and could help to avoid therapy exposure for patients who have a low probability of SVR.