Beijing You'an Hospital, Capital Medical University, Beijing, PR China.
Antiviral Res. 2011 Nov;92(2):247-54. doi: 10.1016/j.antiviral.2011.08.009. Epub 2011 Aug 26.
There have been few studies on the potential immunological factors associated with viral controls in antiviral-experienced patients on a second round of combination therapy. In this study, we evaluated the level of systemic cytokines and potential impact on combination therapy in both antiviral-naïve and -experienced patients chronically infected with hepatitis C virus.
Longitudinal analysis of 27 cytokines and chemokines was performed using the multiplex Biorad 27 plex assay in 37 antiviral-naïve and 24 experienced chronically HCV-1b-infected patients during combination therapy with peginterferon-alfa and ribavirin. A group of healthy donors was included as the control (n=11).
Fifty percent of antiviral-experienced chronically HCV-patients could achieve a delayed and slow virologic response after 48 weeks combination therapy, comparing with an early and fast virologic response in antiviral-naïve patients. A distinction of immune mediators profiling before and during antiviral therapy between antiviral-naïve and -experienced patients was identified, IL-4, IFN-γ and CCL-3 (MIP-1a) were significantly higher in naïve patients than those in experienced patients (P=0.005, 0.047 and 0.017, respectively) while G-CSF in naïve was lower than in experienced patients (P<0.05). Notably, higher Th1 type cytokine IFN-γ and lower Th2 type cytokine IL-4 at baseline and week 4 were associated with HCV clearance in naïve patients, and a similar trend appeared at week 12 in experienced patients.
We found a successful second round therapy in antiviral-experienced patients appears to be associated with the host immune response. Dominant Th1-polar cytokines, especially IFN-γ, is a potential predictor of viral responsiveness.
在第二轮联合治疗中，针对具有抗病毒经验的患者，与病毒控制相关的潜在免疫因素研究较少。在这项研究中，我们评估了慢性丙型肝炎病毒感染的抗病毒初治和有经验患者的全身性细胞因子水平及其对联合治疗的潜在影响。
采用 27 聚体生物辐射多指标分析试剂盒对 37 例抗病毒初治和 24 例慢性 HCV-1b 感染有经验患者的 27 种细胞因子和趋化因子进行了纵向分析，这些患者在接受聚乙二醇干扰素-α和利巴韦林联合治疗期间。纳入一组健康供体作为对照（n=11）。
50%的有经验慢性丙型肝炎患者在 48 周联合治疗后出现延迟和缓慢的病毒学应答，而抗病毒初治患者则出现早期和快速的病毒学应答。在抗病毒初治和有经验患者的抗病毒治疗前后，免疫介质谱存在差异，初治患者的 IL-4、IFN-γ和 CCL-3（MIP-1a）明显高于有经验患者（P=0.005、0.047 和 0.017），而 G-CSF 则低于有经验患者（P<0.05）。值得注意的是，初治患者基线和第 4 周 IFN-γ水平较高、IL-4 水平较低与 HCV 清除有关，而有经验患者第 12 周也出现了类似趋势。
我们发现，有经验患者的第二轮成功治疗似乎与宿主免疫反应有关。优势 Th1 型细胞因子，特别是 IFN-γ，是病毒反应性的潜在预测因子。
