2nd Department of Internal Medicine, Athens University School of Medicine, Hippokration General Hospital of Athens, 11527 Athens, Greece.
World J Gastroenterol. 2012 Nov 14;18(42):6060-9. doi: 10.3748/wjg.v18.i42.6060.
Over the last decade, the standard of care for the treatment of chronic hepatitis C has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin (RBV) which results in sustained virological response (SVR) rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Currently, there are rapid and continuous developments of numerous new agents against hepatitis C virus (HCV), which are the focus of this review. Boceprevir and telaprevir, two first-generation NS3/4A HCV protease inhibitors, have been recently licensed in several countries around the world to be used in combination with PEG-IFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, compared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naïve genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%-28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-naïve patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events (anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir), new drug interactions and increasing difficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG-IFN/RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. Preliminary data suggest that the treatment of chronic HCV patients with well tolerated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.
在过去的十年中，慢性丙型肝炎治疗的标准是聚乙二醇干扰素-α（PEG-IFN）和利巴韦林（RBV）的联合治疗，对于基因型 2 或 3 的患者，其持续病毒学应答（SVR）率为 75%-85%，但对于基因型 1 的患者，其 SVR 率仅为 40%-50%。目前，针对丙型肝炎病毒（HCV）的许多新药物正在快速而持续地发展，这是本次综述的重点。博赛泼维（Boceprevir）和特拉泼维（Telaprevir）是两种第一代 NS3/4A HCV 蛋白酶抑制剂，已在世界上许多国家获得许可，与 PEG-IFN 和 RBV 联合用于治疗基因型 1 患者。与 PEG-IFN/RBV 联合治疗相比，博赛泼维或特拉泼维三联方案使初治基因型 1 患者的 SVR 率提高了 25%-31%，使既往复发患者的 SVR 率提高了 40%-64%，使既往部分应答患者的 SVR 率提高了 33%-45%，使既往无应答患者的 SVR 率提高了 24%-28%。同时，根据治疗过程中的病毒学应答结果应用应答指导治疗算法，使 45%-55%的初治患者的总治疗时间缩短至仅 24 周。然而，在基因型 1 患者中使用新的三联方案存在一些挑战，例如需要使用敏感的定量检测方法立即获得 HCV RNA 检测结果，出现新的且更频繁的不良反应（博赛泼维的贫血和味觉障碍；特拉泼维的瘙痒、皮疹和贫血），出现新的药物相互作用以及治疗依从性的难度增加。此外，在一些难以治疗的基因型 1 患者亚组中，如肝硬化的无应答患者，SVR 率仍然很差，而对于不能耐受 PEG-IFN/RBV 或感染非 1 型 HCV 基因型的患者，SVR 率并没有获益。目前，许多不同类别的新型抗 HCV 药物及其多种组合正在进行评估，结果令人鼓舞。初步数据表明，使用无 PEG-IFN 的口服药物的耐受性良好的联合方案治疗慢性丙型肝炎患者是可行的，可能会在未来 5-10 年内实现丙型肝炎的普遍治愈。
