Lymphotropic hepatitis C virus has an interferon‐resistant phenotype
Lymphotropic hepatitis C virus has an interferon‐resistant phenotype
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嗜淋巴细胞丙型肝炎病毒具有干扰素耐药表型
DOI：
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发表时间：
2012
影响因子：
2.5
通讯作者：
M. Imawari
中科院分区：
文献类型：
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作者：
Momoko Inokuchi;Takayoshi Ito;H. Nozawa;Miyuki Miyashita;Kenichi Morikawa;Manabu Uchikoshi;Yuu Shimozuma;Jun Arai;Tomoe Shimazaki;K. Hiroishi;M. Imawari
丙型肝炎病毒(丙型肝炎病毒)感染并与B细胞相关，导致B细胞异常激活，并发展为淋巴增生性疾病和自身免疫性疾病。这种免疫紊乱可能反过来与丙型肝炎病毒对宿主免疫系统的抵抗力有关。本研究的目的是分析B细胞感染丙型肝炎病毒对干扰素治疗效果的影响。这项研究招募了102名慢性丙型肝炎患者，他们接受了聚乙二醇化干扰素和利巴韦林的治疗。比较病毒快速应答者(RVR)与非RVR、持续病毒应答者(SVR)与非SVR、无病毒应答者(NVR)与VR患者B细胞中的HCVRNA滴度。非RVR组、非SVR组和NVR组B细胞中的HCVRNA水平显著高于对照组。治疗结果与B细胞丙型肝炎病毒RNA阳性之间的关系也与其他已知的病毒和宿主因素有关。多变量分析显示，B细胞HCVRNA阳性和IL28B基因附近的微小单核苷酸多态(Rs8099917)是与NVR相关的独立因素。当这两个因素联合使用时，NVR的敏感性、特异性、阳性预测值和阴性预测值分别为92.3%、98.2%、92.3%和98.2%。基因型1和干扰素敏感性决定区存在一个或没有突变与较高水平的B细胞丙型肝炎病毒RNA相关。嗜B细胞的丙型肝炎病毒似乎具有干扰素耐药表型。B细胞丙型肝炎病毒RNA阳性是干扰素治疗耐药的预测因素。
Summary. Hepatitis C virus (HCV) infects and associates with B cells, leading to abnormal B‐cell activation and development of lymphoproliferative and autoimmune disorders. This immune perturbation may in turn be associated with the resistance of HCV against the host immune system. The objective of this study was to analyse the effects of HCV infection of B cells on the efficacy of interferon (IFN)‐based therapy. The study enrolled 102 patients with chronic hepatitis C who were treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were compared in patients with rapid viral responder (RVR) vs non‐RVR, sustained viral responder (SVR) vs non‐SVR and null viral responder (NVR) vs VR. The levels of HCV RNA in B cells were significantly higher in non‐RVR, non‐SVR and NVR groups. Association between the therapy outcome and the positive B‐cell HCV RNA was also investigated in relation to other known viral and host factors. Multivariable analyses showed that the positive B‐cell HCV RNA and the minor single‐nucleotide polymorphism near the IL28B gene (rs8099917) were independent factors associated with NVR in patients infected with HCV genotype 1. When these two factors were combined, the sensitivity, specificity, positive and negative predictive values for NVR were 92.3%, 98.2%, 92.3% and 98.2%, respectively. Genotype 1 and the presence of one or no mutations in the IFN‐sensitivity determining region were associated with higher levels of B‐cell HCV RNA. B‐cell‐tropic HCV appears to have an IFN‐resistant phenotype. B‐cell HCV RNA positivity is a predictive factor for resistance to IFN‐based therapy.
DOI：
10.1016/s0928-0197(98)00034-8
发表时间：
1998-07
期刊：
Clinical and diagnostic virology
影响因子：
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作者：
M. Gale;M. J. Korth;M. Katze
通讯作者：
M. Gale;M. J. Korth;M. Katze