利巴韦林治疗慢性丙型肝炎的机制目前尚不清楚。微列分析显示利巴韦林可以增强干扰素刺激基因的诱导作用。在干扰素联合利巴韦林或单独治疗慢性丙型肝炎的早期，我们对病毒动力学，血清细胞因子表达和病毒突变进行了分析。50名基因1型的慢性丙肝患者被随机分配到两个组。一组进行48周的联合治疗，另一组前4周不服用利巴韦林，在随后的44周进行联合治疗。对病毒动力学的一期和二期进行评估。IP10，MIG和MCP1作为干扰素刺激基因产物进行定量。在两组中一期病毒下降相似。服用利巴韦林的患者比未服用利巴韦林的患者二期病毒下降更快，在12小时，联合治疗的患者比干扰素单独治疗的患者血清IP10表达高，这有差异在一期应答好的患者中更为明显。IP10的表达与一期二期动力学及第3天的利巴韦林血清学浓度具有相关性。 利巴韦林促进了对长效干扰素有原始应答患者的早期病毒学应答。随着利巴韦林的治疗，干扰素刺激基因诱导的细胞因子与病毒动力学相关，表明利巴韦林增强了干扰素信号肽。
吉林大学第一医院肝胆胰内科 吕娟 牛俊奇 摘译
本文首次发表于[Gastroenterology, 2010, 139(1): 154-62.e4. ]
Ribavirin improves early responses to peginterferon through improved interferon signaling
Background & Aims: The therapeutic mechanisms of ribavirin for hepatitis C are unclear. Microarray analyses have shown that ribavirin increases induction of interferon-stimulated genes(ISGs). We evaluated viral kinetics, serum cytokine expression, and viral mutagenesis during early stages of peginterferon therapy with and without ribavirin. Methods: Fifty patients with chronic hepatitis C virus (HCV) infection genotype 1 were randomly assigned to groups that were given peginterferon alfa-2a, with or without ribavirin, for 4 weeks; all patients then received an additional 44 weeks of combination therapy. First- and second-phase viral kinetics were evaluated. Serum levels of IP10, MIG, and MCP1 were quantified as measures of the ISG response. Results: The first-phase decrease in HCV RNA was similar between groups. Patients that received ribavirin had a more rapid second-phase decrease, compared with patients that did not receive ribavirin—particularly those with an adequate first-phase decrease (0.61 vs. 0.35 log10 IU/mL/week, p=0.018). At 12 hrs, fold induction of serum IP10 was higher in patients given the combination therapy than those given only peginterferon (7.6- vs. 3.8-fold, p=0.01); however, the difference was greatest in patients with an adequate first-phase decrease in HCV RNA. IP10-induction correlated with first- and second-phase kinetics and with ribavirin serum concentrations on day 3. Conclusion: Ribavirin improves the kinetics of the early response to therapy in patients with an adequate initial response to peginterferon. Induction of interferon-stimulated cytokines correlates with viral kinetics following ribavirin therapy, suggesting that ribavirin promotes interferon signaling.
