Hepatitis C virus (HCV) causes persistent infection and invades host's innate and adaptive immune systems. During the eradication of this pathogen, the components of immune system may cause bystander damage to host, which might be even worse than the viral pathogenesis. Thus, the therapy should not only eliminate primary virus infection but also improve the inflammatory immune responses. The breakthrough of interferon free direct acting antiviral (DAA) drugs has provided the opportunity to unravel the association of HCV with immune response. This study aimed to examine the expression level of C-X-C motif chemokine ligand 10 (CXCL10) in the Peripheral blood mononuclear cells (PBMCs) of HCV infected patients treated with DAAs + Ribavirin. In this study we analyzed the expression levels of CXCL10 mRNA in the 90 chronic HCV patients using quantitative PCR (qPCR) prior, after, and during therapy with sofosbuvir/ribavirin (SOF+RBV) and sofosbuvir/daclatasvir/ribavirin (SOF+DCV+RBV), and further, the results were analyzed relative to treatment response. Significantly elevated CXCL10 mRNA was seen in naive patients having higher viral load (P = 0.005) and those suffering from hepatocellular carcinoma (P = 0.006). HCV patients had remarkable decline in CXCL10 level after 4, 12, and 24 weeks of therapy with DAAs. An approximate one-fold decrease was observed in patients who attained sustained virological response compared to untreated patients (P < 0.0001). Comparing the 2 regimens, the reduction in peripheral CXCL10 expression was more pronounced in patients undergoing SOF+DCV+RBV therapy. The current study implicitly shows the role of CXCL10 as an indicator of disruption of host-virus equilibrium and consequent pathogenesis of HCV during successful antiviral therapy. Furthermore, the drop in CXCL10 level after HCV viral clearance might reflect the DAA-induced alleviation in the extrahepatic manifestation of this infection.

中文翻译：

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用Sofosbuvir，Daclatasvir和Ribavirin治疗的慢性丙型肝炎患者中CXCL10基因的外周表达。

丙型肝炎病毒（HCV）引起持续感染，并侵入宿主的先天和适应性免疫系统。在消灭这种病原体的过程中，免疫系统的组成部分可能对宿主造成旁观者损害，甚至可能比病毒的发病机理更为严重。因此，该疗法不仅应消除原发性病毒感染，而且应改善炎性免疫反应。无干扰素的直接作用抗病毒药物的突破提供了机会来阐明HCV与免疫反应的关系。这项研究旨在检查在用DAA +利巴韦林治疗的HCV感染患者的外周血单个核细胞（PBMC）中CXC基序趋化因子配体10（CXCL10）的表达水平。在这项研究中，我们分析了CXCL10的表达水平在使用Sofosbuvir /利巴韦林（SOF + RBV）和sofosbuvir / daclatasvir /利巴韦林（SOF + DCV + RBV）治疗之前，之后和过程中使用定量PCR（qPCR）对90例慢性HCV患者的mRNA进行分析，并进一步分析结果相对于治疗反应。在病毒载量较高（P  = 0.005）和肝细胞癌患者（P  = 0.006）的未治疗患者中，发现CXCL10 mRNA显着升高。HCV患者在用DAA治疗4、12和24周后CXCL10水平显着下降。与未治疗的患者相比，在获得持续病毒学应答的患者中观察到大约减少了一倍（P<0.0001）。比较这两种方案，接受SOF + DCV + RBV治疗的患者外周CXCL10表达的降低更为明显。当前的研究隐含地显示了CXCL10在成功的抗病毒治疗过程中作为宿主病毒平衡破坏和随后HCV发病机理的指标的作用。此外，HCV病毒清除后CXCL10水平下降可能反映了DAA诱导的这种感染肝外表现的减轻。