Combination treatment for chronic hepatitis C: what is the role of ribavirin?

Ribavirin in combination with interferon-alpha2b is the new standard for chronic hepatitis C (CHC) treatment. Although usually considered as an antiviral compound, this guanosine analogue shows some additional effects on the immune system that could largely contribute to its clinical efficacy in CHC. Numerous in vitro experiments demonstrate that ribavirin has a selective down-regulatory effect on TH2 cytokine release with, in some cases, a concomitant TH1 cytokine up-regulation. In vivo, combination treatment of CHC patients was shown to induce a predominant TH1 response in isolated PBMCs, but also a reduction of peripheral TH2 response. Considering that: 1) a strong CD(4)+ helper T-cell response is associated with viral clearance in acutely infected patients; 2) a weak T-cell response to the viral antigens is common in chronic infected patients; 3) responding patients to combination treatment (but not non-responding patients) altered their cytokine profile under treatment, either to express IFN-gamma or to reduce pro-inflammatory mediators; it is highly presumed that ribavirine participates to restore an efficient T-cell response and to reduce the non-specific inflammatory cytolytic activity during CHC combination treatment.