Introduction: Therapy for HCV has relied on the cytokine interferon-alpha (IFN-α) and the anti-viral nucleoside analogue ribavirin, with response rates often suboptimal, particularly in those infected with genotype 1. The introduction of NS-4A protease inhibitors to dual therapy increases response rates from below 50% up to 75% in genotype 1 infected patients; however this triple therapy can have severe side effects and substantial economic cost.
Aim: We aimed to identify patients who would respond to standard IFN-α therapy by analysing in vitro responsiveness to IFN-α pre-treatment, thus identifying patients who would not require additional protease inhibitors.
Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from HCV patients (n=45; genotype 1 n=19, genotype non-1 n=26) before they commenced therapy and stimulated with IFN-α. Anti-viral IFN stimulated genes (ISGs) were measured using quantitative real-time PCR. Pre-treatment ISG expression was correlated with subsequent clinical response to therapy.
Results: Patients infected with genotype 1 of HCV who achieved SVR (n=8) had significantly higher expression of the ISGs PKR (p<0.05), OAS (p<0.01) and MxA (p<0.01) in IFN-α stimulated PBMCs taken before they commenced therapy, compared to genotype 1 infected patients who did not achieve SVR (n=8). Correlation between ISG expression and SVR was stronger than correlation with either rapid virological response (RVR) or early virological response (EVR). Pre-treatment ISG expression could not predict clinical responsiveness of patients infected with other genotypes.
Conclusion: In vitro responsiveness of PBMCs from genotype 1 patients could predict clinical response to IFN-α therapy. Analysis of these patients pre-treatment identified patients who would not require additional protease inhibitors, thus improving quality of life and making significant economic savings.