Department of Infectious Diseases, Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
J Med Virol. 2019 Feb;91(2):278-286. doi: 10.1002/jmv.25302. Epub 2018 Sep 24.
Currently, hepatitis C antiviral therapy is entering a new era with the use of direct-acting antiviral (DAA) agents. However, the precise immunological influences of DAA therapy in patients with chronic hepatitis C (CHC) are insufficiently understood. This study aimed to investigate the effects of DAA therapy on the frequency of myeloid-derived suppressor cells (MDSCs), T lymphocytes, and natural killer (NK) cells in patients with CHC. Thirty-two treatment-naive CHC patients were treated with DAA therapy, and the frequency of immune cells was analyzed by flow cytometry at various time points during and after therapy. Sixteen healthy donors were recruited for comparison. DAA therapy decreased the frequency of MDSCs and monocytic MDSCs in patients with CHC to a normal level. DAA therapy also increased the CD8 T and NK cell levels in patients with CHC. In addition, activation (NKp30 and NKp46) and inhibitory (NKG2A) receptors on NK cells were downregulated to yield an NK cell phenotype resembling that observed in the healthy controls. This study provides insight into the normalization of immune cell levels under DAA therapy and indicates that restoration of the immune system in patients with CHC strongly supports long-term curative hepatitis C virus eradication.
目前，直接作用抗病毒（DAA）药物的应用使丙型肝炎抗病毒治疗进入了一个新时代。然而，人们对 DAA 治疗对慢性丙型肝炎（CHC）患者的精确免疫影响了解不足。本研究旨在探讨 DAA 治疗对 CHC 患者髓样来源抑制细胞（MDSC）、T 淋巴细胞和自然杀伤（NK）细胞频率的影响。32 例初治 CHC 患者接受 DAA 治疗，通过流式细胞术在治疗期间和治疗后不同时间点分析免疫细胞的频率。招募了 16 名健康供体进行比较。DAA 治疗将 CHC 患者 MDSC 和单核细胞来源 MDSC 的频率降低至正常水平。DAA 治疗还增加了 CHC 患者的 CD8 T 和 NK 细胞水平。此外，NK 细胞上的激活（NKp30 和 NKp46）和抑制（NKG2A）受体被下调，产生类似于健康对照观察到的 NK 细胞表型。本研究深入了解了 DAA 治疗下免疫细胞水平的正常化，并表明恢复 CHC 患者的免疫系统强烈支持长期治愈丙型肝炎病毒的清除。
