Baker Danial E
College of Pharmacy, Washington State University, Spokane, WA, USA.
Rev Gastroenterol Disord. 2003 Spring;3(2):93-109.
Peginterferon alfa-2a and peginterferon alfa-2b have been approved for the treatment of chronic hepatitis C virus (HCV) infection in adults who have compensated liver disease and have not been previously treated with interferon alfa. Peginterferon alfa-2a and peginterferon alfa-2b have also been approved for use in combination with ribavirin as therapy for these adults. Combining peginterferon alfa-2a or alfa-2b with ribavirin produces better activity against HCV than either drug alone. Interferon works by binding to specific receptors on the cell surface that initiate a complex cascade of protein-protein interactions leading to rapid activation of gene transcription. The effects of this interferon-stimulated gene modulation depend on the biologic system and may result in the inhibition of viral replication in infected cells, inhibition of cell proliferation, and immunomodulation. Pegylation of the interferon molecule increases its size; the absorption of the larger pegylated molecule is slower, its half-life is longer, and its rate of clearance from the plasma is lower than that of the native interferon. Thus, the pegylated molecule increases the duration of biologic activity. Factors that appear to influence the success of pegylated interferon therapy are HCV genotype, baseline viral load, presence of fibrosis or inflammation shown on the liver biopsy at baseline, and the patient's body weight or body surface area. Patients infected with HCV genotype 1 tend to have a lower response rate, require longer courses of therapy, and respond better when treated with a pegylated interferon plus ribavirin. Patients infected with HCV genotypes 2 or 3 have comparable responses when treated with interferon plus ribavirin or pegylated interferon plus ribavirin and can be treated with a lower dose of ribavirin and a shorter course of therapy (24 weeks vs 48 weeks for patients with genotype 1). Studies directly comparing peginterferon alfa-2a and peginterferon alfa-2b have not been performed.
聚乙二醇化干扰素α-2a和聚乙二醇化干扰素α-2b已被批准用于治疗患有代偿性肝病且既往未接受过干扰素α治疗的成年慢性丙型肝炎病毒（HCV）感染者。聚乙二醇化干扰素α-2a和聚乙二醇化干扰素α-2b也已被批准与利巴韦林联合用于这些成年人的治疗。聚乙二醇化干扰素α-2a或α-2b与利巴韦林联合使用对HCV的活性比单独使用任何一种药物都更好。干扰素通过与细胞表面的特定受体结合发挥作用，这些受体引发一系列复杂的蛋白质-蛋白质相互作用，导致基因转录迅速激活。这种干扰素刺激的基因调节作用取决于生物系统，可能导致感染细胞中病毒复制的抑制、细胞增殖的抑制以及免疫调节。干扰素分子的聚乙二醇化增加了其大小；较大的聚乙二醇化分子吸收较慢，半衰期较长，从血浆中的清除率低于天然干扰素。因此，聚乙二醇化分子增加了生物活性的持续时间。似乎影响聚乙二醇化干扰素治疗成功的因素包括HCV基因型、基线病毒载量、基线肝活检显示的纤维化或炎症的存在以及患者的体重或体表面积。感染HCV基因型1的患者往往应答率较低，需要更长疗程的治疗，而在接受聚乙二醇化干扰素加利巴韦林治疗时应答较好。感染HCV基因型2或3的患者在接受干扰素加利巴韦林或聚乙二醇化干扰素加利巴韦林治疗时应答相当，并且可以用较低剂量的利巴韦林和较短疗程的治疗（基因型1的患者为24周，而不是48周）。尚未进行直接比较聚乙二醇化干扰素α-2a和聚乙二醇化干扰素α-2b的研究。
