Rajani A K, Ravindra B K, Dkhar S A
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
J Postgrad Med. 2013 Jan-Mar;59(1):42-7. doi: 10.4103/0022-3859.109493.
Chronic hepatitis C is a major public health problem and its burden is expected to increase in the near future. Out of six genotypes of hepatitis C virus (HCV) identified, genotype 1 is the most prevalent genotype in America and Europe. With peg-interferon alpha and ribavirin dual therapy, sustained virological response (SVR) is achieved in less than half of the patients infected with HCV genotype 1. Moreover, this dual therapy also causes many intolerable adverse effects. Telaprevir is an HCV protease inhibitor approved for chronic hepatitis C genotype 1 mono-infection. It is a type of direct acting antiviral drug acting through inhibition of viral non-structural 3/4A protease. It can be safely administered in mild hepatic dysfunction. Due to inhibition of CYP3A4 and P-glycoprotein, significant drug-drug interactions are possible with telaprevir. Trials have shown significantly higher SVR rates when telaprevir is added to peg-interferon alpha and ribavirin, particularly in patients with unfavorable prognostic factors. It is approved for use in treatment-naïve and previously treated patients. Rash and anemia are the major troublesome side-effects. Next-generation protease inhibitors may overcome the drawbacks of telaprevir and another approved HCV protease inhibitor - boceprevir. Evidence from small scale studies suggests that telaprevir may be used in conditions like HIV co-infection, post-transplantation and some HCV non-1 genotype infections also. Preliminary data show higher SVR rates with triple therapy even in patients with unfavorable interleukin-28B (IL28B) genotype. With development of other direct acting antivirals, it might be possible to treat chronic hepatitis C with interferon-free regimens in future. This article briefly reviews the properties of telaprevir and its status in the context of rapidly evolving aspects of management of chronic hepatitis C.
慢性丙型肝炎是一个重大的公共卫生问题,预计其负担在不久的将来还会增加。在已确定的六种丙型肝炎病毒(HCV)基因型中,1型是美国和欧洲最常见的基因型。采用聚乙二醇干扰素α和利巴韦林联合治疗时,感染HCV 1型的患者中不到一半能实现持续病毒学应答(SVR)。此外,这种联合治疗还会引起许多难以耐受的不良反应。特拉匹韦是一种被批准用于慢性丙型肝炎1型单一感染的HCV蛋白酶抑制剂。它是一种直接作用抗病毒药物,通过抑制病毒非结构3/4A蛋白酶发挥作用。它可安全用于轻度肝功能不全患者。由于抑制CYP3A4和P-糖蛋白,特拉匹韦可能会产生显著的药物相互作用。试验表明,在聚乙二醇干扰素α和利巴韦林中添加特拉匹韦时,SVR率显著更高,尤其是在具有不良预后因素的患者中。它被批准用于初治和经治患者。皮疹和贫血是主要的麻烦副作用。新一代蛋白酶抑制剂可能会克服特拉匹韦和另一种已批准的HCV蛋白酶抑制剂——博赛匹韦的缺点。小规模研究的证据表明,特拉匹韦也可用于如HIV合并感染、移植后以及一些HCV非1型基因型感染等情况。初步数据显示,即使在白细胞介素-28B(IL28B)基因型不良的患者中,三联疗法的SVR率也更高。随着其他直接作用抗病毒药物的研发,未来有可能采用无干扰素方案治疗慢性丙型肝炎。本文简要回顾了特拉匹韦的特性及其在慢性丙型肝炎治疗快速发展背景下的地位。