J. W. Goethe University Hospital, Department of Medicine, 1, Theodor-Stern-Kai 7, 60590 Frankfurt/Main, Germany.
Expert Opin Pharmacother. 2012 Mar;13(4):593-606. doi: 10.1517/14656566.2012.660524. Epub 2012 Feb 15.
More than 180 million people worldwide are infected with the chronic hepatitis C virus (HCV), a major cause of liver cirrhosis, and its life-threatening complications including liver failure, portal hypertension and hepatocellular carcinoma. For patients infected with HCV genotype 1, the chances of a sustained virologic response (SVR) with the previous standard of care treatment (Peg-IFN-α + ribavirin) are only 40 - 50%. Neither drug targets a specific HCV protein, and treatment is not only compromised by insufficient SVR rates but also associated with several side effects. With a better understanding of the HCV life-cycle, and of the structural features of HCV proteins, several promising direct antiviral drugs (DAAs) have entered clinical development.
This review summarizes the clinical development of telaprevir and discusses the possible role of telaprevir in combination with Peg-IFN-α and ribavirin as a new standard treatment against HCV infection, as well as any possible challenges in the future.
Triple therapy, with telaprevir in combination with Peg-IFN-α + ribavirin, is the new standard for chronic hepatitis C treatment in genotype 1-infected patients. At present, there are several next-generation DAAs in clinical development in combination with Peg-IFN-α. The future, however, may also include new treatment strategies, such as oral DAA combinations.
全球有超过 1.8 亿人感染慢性丙型肝炎病毒（HCV），这是肝硬化的主要病因，也是危及生命的并发症的主要病因，包括肝功能衰竭、门静脉高压和肝细胞癌。对于感染 HCV 基因型 1 的患者，前标准护理治疗（聚乙二醇干扰素-α+利巴韦林）持续病毒学应答（SVR）的机会只有 40-50%。这两种药物都不是针对 HCV 蛋白的特定靶点，而且治疗不仅受到 SVR 率不足的影响，还与几种副作用有关。随着对 HCV 生命周期和 HCV 蛋白结构特征的更好理解，几种有前途的直接抗病毒药物（DAAs）已进入临床开发。
这篇综述总结了特拉普韦的临床开发情况，并讨论了特拉普韦与聚乙二醇干扰素-α和利巴韦林联合应用作为 HCV 感染新的标准治疗方法的可能作用，以及未来可能面临的任何挑战。
三联疗法，即特拉普韦联合聚乙二醇干扰素-α+利巴韦林，是治疗 1 型感染患者慢性丙型肝炎的新标准。目前，有几种下一代 DAAs 与聚乙二醇干扰素-α联合处于临床开发阶段。然而，未来可能还包括新的治疗策略，如口服 DAA 联合治疗。
