Larrubia Juan-Ramón, Moreno-Cubero Elia, Miquel Joaquín, Sanz-de-Villalobos Eduardo
Juan-Ramón Larrubia, Elia Moreno-Cubero, Joaquín Miquel, Eduardo Sanz-de-Villalobos, Translational Hepatology Unit, Guadalajara University Hospital, University of Alcalá, 19002 Guadalajara, Spain.
World J Gastroenterol. 2015 Mar 28;21(12):3480-91. doi: 10.3748/wjg.v21.i12.3480.
Hepatitis C virus (HCV)-specific cytotoxic T cell (CTL) response plays a major role in viral control during spontaneous infection resolution. These cells develop an exhausted and pro-apoptotic status during chronic onset, being unable to get rid of HCV. The role of this response in contributing to sustained viral response (SVR) after anti-HCV is controversial. Recent studies show that after successful interferon-based anti-HCV treatment, HCV traces are still detectable and this correlates with a peak of HCV-specific CTL response activation, probably responsible for maintaining SVR by subsequent complete HCV clearing. Moreover, SVR patients' serum is still able to induce HCV infection in naïve chimpanzees, suggesting that the infection could be under the control of the immune system after a successful treatment, being transmissible in absence of this adaptive response. At least theoretically, treatment-induced viral load decrease could allow an effective HCV-specific CTL response reestablishment. This effect has been recently described with anti-HCV interferon-free regimes, based on direct-acting antivirals. Nevertheless, this is to some extent controversial with interferon-based therapies, due to the detrimental immunoregulatory α-interferon effect on T cells. Moreover, HCV-specific CTL response features during anti-HCV treatment could be a predictive factor of SVR that could have clinical implications in patient management. In this review, the recent knowledge about the role of HCV-specific CTL response in the development of SVR after anti-HCV treatment is discussed.
丙型肝炎病毒（HCV）特异性细胞毒性T细胞（CTL）反应在自发感染消退过程中的病毒控制中起主要作用。在慢性发病期间，这些细胞会进入耗竭和促凋亡状态，无法清除HCV。这种反应在抗HCV治疗后促成持续病毒学应答（SVR）中的作用存在争议。最近的研究表明，基于干扰素的抗HCV治疗成功后，仍可检测到HCV痕迹，这与HCV特异性CTL反应激活的峰值相关，可能是通过随后完全清除HCV来维持SVR的原因。此外，SVR患者的血清仍能够在未感染的黑猩猩中诱导HCV感染，这表明在成功治疗后感染可能处于免疫系统的控制之下，在缺乏这种适应性反应的情况下具有传染性。至少从理论上讲，治疗引起的病毒载量降低可以使有效的HCV特异性CTL反应重新建立。最近基于直接作用抗病毒药物的无抗HCV干扰素方案已经描述了这种效果。然而，由于α干扰素对T细胞具有有害的免疫调节作用，这在某种程度上与基于干扰素的疗法存在争议。此外，抗HCV治疗期间HCV特异性CTL反应特征可能是SVR的预测因素，这可能对患者管理具有临床意义。在这篇综述中，讨论了关于HCV特异性CTL反应在抗HCV治疗后SVR发展中的作用的最新知识。
