The effect of cytokine profiles on the viral response to re-treatment in antiviral-experienced patients with chronic hepatitis C virus infection

Background

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.

Methods

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).

Results

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.

Conclusions

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.