Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Int J Mol Sci. 2020 Oct 10;21(20):7473. doi: 10.3390/ijms21207473.
Chronic HCV (CHC) infection is the only chronic viral infection for which curative treatments have been discovered. These direct acting antiviral (DAA) agents target specific steps in the viral replication cycle with remarkable efficacy and result in sustained virologic response (SVR) or cure in high (>95%) proportions of patients. These treatments became available 6-7 years ago and it is estimated that their real impact on HCV related morbidity, including outcomes such as cirrhosis and hepatocellular carcinoma (HCC), will not be known for the next decade or so. The immune system of a chronically infected patient is severely dysregulated and questions remain regarding the immune system's capacity in limiting liver pathology in a cured individual. Another important consequence of impaired immunity in patients cleared of HCV with DAA will be the inability to generate protective immunity against possible re-infection, necessitating retreatments or developing a prophylactic vaccine. Thus, the impact of viral clearance on restoring immune homeostasis is being investigated by many groups. Among the important questions that need to be answered are how much the immune system normalizes with cure, how long after viral clearance this recalibration occurs, what are the consequences of persisting immune defects for protection from re-infection in vulnerable populations, and does viral clearance reduce liver pathology and the risk of developing hepatocellular carcinoma in individuals cured with these agents. Here, we review the recent literature that describes the defects present in various lymphocyte populations in a CHC patient and their status after viral clearance using DAA treatments.
慢性 HCV（CHC）感染是唯一发现可治愈的慢性病毒感染。这些直接作用抗病毒（DAA）药物针对病毒复制周期中的特定步骤，具有显著疗效，导致持续病毒学应答（SVR）或治愈，患者比例高达 95%以上。这些治疗方法在 6-7 年前就已经问世，预计其对 HCV 相关发病率的实际影响，包括肝硬化和肝细胞癌（HCC）等结果，在未来十年左右内不会被知晓。慢性感染患者的免疫系统严重失调，治愈个体中免疫系统限制肝脏病理的能力仍存在疑问。另一个重要后果是，DAA 清除 HCV 的患者免疫受损，将无法产生针对可能再次感染的保护性免疫，需要进行再次治疗或开发预防性疫苗。因此，许多研究小组正在研究病毒清除对恢复免疫平衡的影响。需要回答的重要问题包括治愈后免疫系统恢复正常的程度、清除病毒后多久发生这种重新调整、持续免疫缺陷对易感染人群免受再次感染的保护有何后果，以及病毒清除是否可以减少个体的肝脏病理和发生肝细胞癌的风险。在这里，我们回顾了最近的文献，描述了 CHC 患者中各种淋巴细胞群存在的缺陷及其在使用 DAA 治疗清除病毒后的状态。
