Pawlotsky Jean Michel
Department of Virology (EA 3489), Hôpital Henri Mondor, Université Paris XII, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil, France.
Antiviral Res. 2003 Jun;59(1):1-11. doi: 10.1016/s0166-3542(03)00088-3.
The treatment of chronic hepatitis C is currently based on a combination of pegylated interferon (IFN)-alpha and ribavirin. When successful, this treatment leads to sustained HCV clearance which, in virtually all cases, signifies viral eradication. However, approximately 20% of patients with hepatitis C virus (HCV) genotype 2 or 3 infection, and 50% of patients with genotype 1 infection, fail to eradicate the virus. The risk of treatment failure is related to multiple factors, including the treatment schedule, adherence of therapy, host factors, and the severity of HCV-associated disease. Viral factors can also lead to true "HCV resistance". The mechanisms underlying this resistance are unknown, but indirect evidence suggests that chronic infection is associated with phenomena that protect HCV from the antiviral action of IFN-alpha and hinder the clearance of infected cells. This article discusses current knowledge of the mechanisms of action of IFN-alpha and ribavirin, the virological characteristics of chronic hepatitis C treatment success and failure, and possible underlying mechanisms.
目前，慢性丙型肝炎的治疗是基于聚乙二醇化干扰素（IFN）-α和利巴韦林联合使用。治疗成功时，这种疗法可实现丙型肝炎病毒（HCV）的持续清除，实际上在所有病例中，这都意味着病毒被根除。然而，约20%的丙型肝炎病毒（HCV）2型或3型感染患者以及50%的1型感染患者无法根除病毒。治疗失败的风险与多种因素有关，包括治疗方案、治疗依从性、宿主因素以及HCV相关疾病的严重程度。病毒因素也可导致真正的“HCV耐药”。这种耐药的潜在机制尚不清楚，但间接证据表明，慢性感染与一些现象有关，这些现象可保护HCV免受IFN-α的抗病毒作用，并阻碍受感染细胞的清除。本文讨论了目前关于IFN-α和利巴韦林作用机制、慢性丙型肝炎治疗成败的病毒学特征以及可能的潜在机制的知识。
