Pawlotsky Jean-Michel
Hôpital Henri Mondor, Créteil, France.
Hepatology. 2006 Feb;43(2 Suppl 1):S207-20. doi: 10.1002/hep.21064.
The complications of chronic hepatitis C virus infection can be prevented by antiviral therapy. The initial choice of interferon alfa and, subsequently, ribavirin as potential treatments for chronic hepatitis C was empirical. Nevertheless, the combination of pegylated interferon alfa and ribavirin has become the standard treatment of chronic hepatitis C. Since the advent of interferon-based therapy, enormous progress has been made in understanding the mechanisms of treatment efficacy and failure, and in everyday patient management. The principal advances are: a better understanding of hepatitis C virus steady-state kinetics and the antiviral mechanisms of interferon and ribavirin; easier treatment decisions thanks to novel assays to assess liver disease severity and the virological characteristics of infection; a better use of virological tests to tailor therapy; a better management of adverse effects; a better understanding of virological treatment failure; and a better management of "special" populations, including patients with decompensated cirrhosis and end-stage liver disease, liver transplant recipients, hemodialysis patients and renal transplant recipients, human immunodeficiency virus-coinfected patients, intravenous drug users and patients on opiate replacement therapy, or virological non responders to previous therapies. Steady-state HCV kinetics offers several potential targets for new drugs. These targets should ideally be hit simultaneously in order to achieve viral eradication within a reasonable time frame. Future drugs for HCV infection will belong to four main categories, including new interferons, alternatives to ribavirin, specific HCV inhibitors, and immune modulators. New treatments and vaccines might make it possible to eradicate HCV in the future.
慢性丙型肝炎病毒感染的并发症可通过抗病毒治疗来预防。最初选择干扰素α，随后选择利巴韦林作为慢性丙型肝炎的潜在治疗方法是基于经验的。然而，聚乙二醇化干扰素α与利巴韦林联合使用已成为慢性丙型肝炎的标准治疗方法。自从基于干扰素的治疗方法出现以来，在理解治疗疗效和失败的机制以及日常患者管理方面取得了巨大进展。主要进展包括：对丙型肝炎病毒稳态动力学以及干扰素和利巴韦林的抗病毒机制有了更好的理解；由于有了评估肝病严重程度和感染病毒学特征的新检测方法，治疗决策更加容易；更好地利用病毒学检测来调整治疗方案；更好地管理不良反应；更好地理解病毒学治疗失败；以及更好地管理“特殊”人群，包括失代偿期肝硬化和终末期肝病患者、肝移植受者、血液透析患者和肾移植受者、合并人类免疫缺陷病毒感染的患者、静脉吸毒者以及接受阿片类药物替代治疗的患者，或对先前治疗无病毒学应答的患者。稳态丙型肝炎病毒动力学为新药提供了几个潜在靶点。为了在合理的时间框架内实现病毒根除，理想情况下应同时作用于这些靶点。未来用于丙型肝炎病毒感染的药物将主要分为四类，包括新型干扰素、利巴韦林的替代品、特异性丙型肝炎病毒抑制剂和免疫调节剂。新的治疗方法和疫苗可能使未来根除丙型肝炎病毒成为可能。
