Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections.
Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections.
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慢性丙型肝炎病毒和丙型肝炎病毒感染的抗病毒治疗的免疫学方面。
DOI：
10.1002/hep.27323
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发表时间：
2015-02
期刊：
影响因子：
--
通讯作者：
Bertoletti A
中科院分区：
文献类型：
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作者：
Rehermann B;Bertoletti A
B型肝炎病毒（HBV）和C型肝炎病毒（HCV）在全球范围内引起很大比例的急性和慢性肝病。在过去的几十年里，许多免疫学研究定义了介导急性HBV和HCV感染自发清除的宿主免疫反应。然而，宿主免疫应答也与治疗诱导的慢性HBV和HCV感染清除相关。首先，干扰素刺激基因的治疗前水平以及先天免疫应答的遗传决定因素，如IFNL 3基因附近的单核苷酸多态性，是对基于干扰素-α（IFN-α）的治疗应答的强预测因子。第二，IFN-α（数十年来一直是HBV和HCV治疗的支柱）和利巴韦林（也已被纳入HCV的无干扰素直接抗病毒治疗）调节宿主免疫应答。第三，HBV和HCV感染的基于IFN-α和不含IFN-α的治疗方案都改变了针对这些病毒的短期和长期适应性免疫应答。最后，治疗研究不仅改善了临床结果，还提供了研究病毒-宿主相互作用的机会。这篇综述总结了我们目前的知识，患者的免疫反应如何影响HBV和HCV感染的治疗结果，以及先天性和适应性免疫反应本身如何被不同的治疗方案所改变。
Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause a large proportion of acute and chronic liver disease worldwide. Over the past decades many immunological studies defined host immune responses that mediate spontaneous clearance of acute HBV and HCV infection. However, host immune responses are also relevant in the context of treatment-induced clearance of chronic HBV and HCV infection. First, the pretreatment level of interferon-stimulated genes as well as genetic determinants of innate immune responses, such as single nucleotide polymorphisms near the IFNL3 gene, are strong predictors of the response to interferon-alpha (IFN-α)-based therapy. Second, IFN-α, which has been a mainstay of HBV and HCV therapy over decades, and ribavirin, which has also been included in interferon-free direct antiviral therapy for HCV, modulate host immune responses. Third, both IFN-α-based and IFN-α-free treatment regimens of HBV and HCV infection alter the short-term and long-term adaptive immune response against these viruses. Finally, treatment studies have not just improved the clinical outcomes, but also provided opportunities to study virus-host interaction. This review summarizes our current knowledge on how a patient's immune response affects the treatment outcome of HBV and HCV infection and how innate and adaptive immune responses themselves are altered by the different treatment regimens.