Parfieniuk Anna, Jaroszewicz Jerzy, Flisiak Robert
World J Gastroenterol. 2007 Nov 21;13(43):5673-81. doi: 10.3748/wjg.v13.i43.5673.
Hepatitis C virus (HCV) infection affects 180 million people worldwide with the predominant prevalence being infection with genotype 1, followed by genotypes 2 and 3. Standard anti-HCV therapy currently aims to enhance natural immune responses to the virus, whereas new therapeutic concepts directly target HCV RNA and viral enzymes or influence host-virus interactions. Novel treatment options now in development are focused on inhibitors of HCV-specific enzymes, NS3 protease and NS5B polymerase. These agents acting in concert represent the concept of specifically targeted antiviral therapy for HCV (STAT-C). STAT-C is an attractive strategy in which the main goal is to increase the effectiveness of antiviral responses across all genotypes, with shorter treatment duration and better tolerability. However, the emergence of resistant mutations that limit the use of these compounds in monotherapy complicates the regimens. Thus, a predictable scenario for HCV treatment in the future will be combinations of drugs with distinct mechanisms of action. For now, it seems that interferon will remain a fundamental component of any new anti-HCV therapeutic regimens in the near future; therefore, there is pressure to develop forms of interferon that are more effective, less toxic, and more convenient than pegylated interferon.
丙型肝炎病毒(HCV)感染在全球影响着1.8亿人,其中以基因1型感染最为普遍,其次是基因2型和3型。目前标准的抗HCV治疗旨在增强对该病毒的天然免疫反应,而新的治疗理念则直接针对HCV RNA和病毒酶或影响宿主-病毒相互作用。目前正在研发的新型治疗方案主要集中在HCV特异性酶、NS3蛋白酶和NS5B聚合酶的抑制剂上。这些协同作用的药物代表了针对HCV的特异性靶向抗病毒治疗(STAT-C)的概念。STAT-C是一种有吸引力的策略,其主要目标是提高针对所有基因型的抗病毒反应的有效性,缩短治疗时间并提高耐受性。然而,限制这些化合物在单药治疗中使用的耐药突变的出现使治疗方案变得复杂。因此,未来HCV治疗的一个可预测的方案将是不同作用机制药物的联合使用。目前看来,在不久的将来,干扰素似乎仍将是任何新的抗HCV治疗方案的基本组成部分;因此,迫切需要开发比聚乙二醇化干扰素更有效、毒性更小且更方便的干扰素形式。