慢性丙型肝炎直接抗病毒药物治疗进展

丙型肝炎（丙肝）是全球面临的公共卫生问题,约有1.8亿丙肝病毒（HCV）感染者,每年新增病例300万~400万。国际公认的聚乙二醇干扰素（pegylated interferon,PEG-IFN）α联合利巴韦林（ribavirin,RBV）标准方案（standard of care,SOC）治疗基因1型慢性丙型肝炎（chronic hepatitis C,CHC）的持续病毒学应答（sustained virological response,SVR）率为40%~50%1]。此外,临床上有30%~40%的CHC患者不能耐受SOC不良反应而影响治疗,导致丙肝进展。

Development of direct-acting antiviral agents against chronic hepatitis C

The sustained virological response （SVR） in the treatment of chronic hepatitis C virus （HCV） in- fection using the current standard of care （SOC）, pegylated interferon （PEG-IFN） α combined with ribavirin （RBV）, is about 40%-50%. Approximately 30%-40% of the patients could not tolerate the side effects of PEG-IFN a. During recent years, a lot of efforts have been made for the development of direct-acting antiviral agents （DAAs） against chronic HCV infection. Protease inhibitors boceprevir and telaprevir in combination with PEG-IFN-a and ribavirin （RBV） are the first DAAs approved in the United States for the treatment of genotype I HCV in 2011 and the new combined therapy increased the SVR up to 66 %-75 %. At present, there are more than 35 additional DAAs, including a range of non-structural protein （NS） 3/NS4A protease inhibi- tots, NSSB polymerase inhibitors and NSSA inhibitors in phase II or phase III clinical trials. After 12 weeks of treatment, the SVR rates reached 61%-100 % in both treatment-naive and treatment-experienced patients.