Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study

Decreased expression of interferon‐stimulated genes in B cells of patients with chronic hepatitis C during interferon‐free therapy potentially suggests the eradication of hepatitis C virus in the B cells: A cohort study
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在无干扰素治疗期间,慢性丙型肝炎患者 B 细胞中干扰素刺激基因表达的减少可能表明 B 细胞中丙型肝炎病毒已被根除:一项队列研究

DOI:
10.1002/hsr2.176
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发表时间:
2020
影响因子:
2
通讯作者:
Yoshida Hi
Yoshida Hi
中科院分区:
--
文献类型:
--
作者:
Arai Jun;Ito Takayoshi;Shimozuma Yuu;Uchikoshi Manabu;Nakajima Yoko;Sakaki Masashi;Uozumi Shojiro;Kajiwara Atsushi;Sugiura Ikuya;Otoyama Yumi;Nozawa Hisako;Kurihara Toshikazu;Eguchi Junichi;Nomura Norihiro;Sakuma Dai;Sato Masashi;Deguchi Yoshio;Yoshida Hi

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目的丙型肝炎病毒(HCV)感染受宿主先天免疫的监控,包括内源性干扰素(IFN),它上调干扰素刺激基因(ISGs)。丙型肝炎病毒既亲肝又亲淋巴,但其在淋巴样细胞中的复制是一个有争议的问题。在此,我们分析了丙型肝炎病毒感染者在抗病毒治疗过程中B细胞中ISGs的mRNA水平,并探讨了病毒根除的效果。结果175例持续病毒学应答(SVR)患者中,有133例(76.0%)在治疗前B细胞中检测到了HCVRNA。IL-28B非主要基因携带者B细胞中HCVRNA阳性率较高。大部分患者B细胞中的HCVRNA在抗病毒治疗开始后1周内消失。患者组ISG基因表达水平显著高于正常对照组。在以干扰素为基础的治疗过程中,ISG mRNA水平升高,并一直保持在较高水平。相反,获得SVR的患者在无干扰素治疗1周后ISG mRNA水平显著下降,并在治疗过程中保持在较低水平。结论无干扰素治疗有可能根除B细胞中的丙型肝炎病毒,导致内源性ISGs下调。ISG基因表达水平可作为B细胞病毒清除的指标。
AimsHepatitis C virus (HCV) infection is monitored by the host innate immunity that includes the endogenous interferon (IFN), which up‐regulates IFN‐stimulated genes (ISGs). HCV is both hepatotropic and lymphotropic, but HCV replication in lymphoid cells is a controversial issue. Here, we analyzed the mRNA levels of the ISGs in B cells of HCV‐infected patients during antiviral therapy and investigated the effects of viral eradication.MethodsOne hundred and eighty‐one patients with chronic hepatitis C and 26 healthy volunteers were enrolled in this study. Levels of HCV RNA and mRNA of ISGs in B cells isolated from the patients were monitored before, during, and after antiviral therapy.ResultsHCV RNA was detected in B cells of 133/175 (76.0%) patients who achieved sustained virologic response (SVR) before therapy was started. The positive ratio of HCV RNA in B cells was higher in patients with genotype 1 and the non‐major genotype of interleukin 28B. HCV RNA in B cells of most patients disappeared 1 week after antiviral therapy was started. The baseline expression of ISG mRNA was significantly higher in the patients than in the healthy volunteers. Levels of ISG mRNA were increased and remained high throughout the IFN‐based therapy. In contrast, levels of ISG mRNA in patients who achieved SVR were significantly decreased 1 week after the IFN‐free therapy was started and remained low during the therapy.ConclusionsThese results suggested that IFN‐free therapy potentially eradicated HCV in the B cells, leading to the down‐regulation of endogenous ISGs. The level of ISG mRNA could be used as a marker for viral eradication in B cells.
DOI: 10.1002/ijc.31615
发表时间: 2018-11-15
影响因子: 6.4
作者:
Arai, Jun;Goto, Kaku;Kato, Naoya
通讯作者: Kato, Naoya
对 1000 名基线肝内和外周先天免疫的评估与 DAA 治疗期间丙型肝炎病毒清除相关。
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发表时间: 2018
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发表时间: 2014-05-15
影响因子: 158.5
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发表时间: 2009-04-01
影响因子: 12.7
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