Interferon-stimulated gene expression and hepatitis C viral dynamics during different interferon regimens

Background/Aims: To address the molecular mechanism for enhanced antiviral efficacy associated with a frequent dosing of interferon (IFN)-beta. Methods: Serum hepatitis C viral (HCV) dynamics, double-stranded RNA-activated protein kinase (PKR) mRNA and MxA mRNA levels in peripheral blood mononuclear cells (PBMC) were analyzed serially in 140 patients who were randomly assigned to a twice daily (3 MU bid) or once daily (6 MU qd) administration group. Results: In twice daily group, the rate of HCV decline during the second phase was 2-fold greater than in the once daily group (P = 0.04). Peak PKR and MxA gene expression levels in the first phase (observed 4 h after a single administration) were 2-fold higher in the once daily group. However, the expression in the second phase was maintained at a significantly higher level in the twice daily group. Initial and peak expression levels were related to initial viral load. Basal expressions in PBMC were significantly correlated with those in the liver tissue (PKR, r = 0.81; MxA, r = 0.75, respectively, P < 0.0001). Conclusions: Our data suggest that elimination of HCV-infected cells is enhanced by twice daily dosing of IFN-beta, and that this enhanced effect is associated with a higher intracellular expression of PKR and MxA during the second phase. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.