SUMMARYRecent studies in vitro and in animals have suggested that ribavirin may potentiate the antihepatitis C virus (HCV) activity of interferon-a (IFN-a ) by up-modulating the production of T cell-derived cytokines, such as interleukin (IL)-2 and IFN-g, which play a key role in the cellular immune response against HCV. To study the immune-modulatory mechanisms of ribavirin further, cytokine production by activated T cells and circulating cytokine levels were studied by FACS analysis and ELISA testing in 25 patients with chronic hepatitis C unresponsive to IFN-a , before and after treatment with either ribavirin plus IFN-a or IFN-a alone. After 16 weeks of treatment, both the expression of IFN-g by activated T cells and the blood levels of IFN-g, were significantly reduced with respect to pretreatment values in patients treated with ribavirin and IFN-a but not in those undergoing treatment with IFN-a alone. The expression of IFN-g was significantly lower in patients that gained normal ALT levels with respect to those that did not. No modification of the expression of IL-2, IL-4 and IL-10 was found before and after treatment in either group of patients. In conclusion, the results of this study do not support upmodulation of IFN-g and IL-2 production as the mechanism by which ribavirin potentiates IFN-a anti HCV activity. In addition, our findings suggest that ribavirin may exert an anti-inflammatory effect and may help reducing IFN-g-driven T cell activation and liver damage.

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The M41L, M184V, L210W, and T215Y mutations were associated with a better, although transient, virological outcome in patients treated with efavirenz-based regimens.

SUMMARYA T helper (Th)1 to Th2 shift has been proposed to be a critical pathogenic determinant in chronic hepatitis C. Here, we evaluated mitogen-induced and hepatitis C virus (HCV) core antigen-induced cytokine production in 28 patients with biopsy-proven chronic hepatitis C. Flow cytometry demonstrated that after mitogenic stimulation the percentage of Th2 cells (IL-4 1 or IL-13 1) and Th0 cells (IFN-g/ IL-4 1 or IL-2/IL-13 1) did not differ between patients and controls. In contrast, the percentage of Th1 cells (IFN-g 1 or IL-2 1) was significantly increased in CD4 1 , CD8 1 ,`naive'-CD45RA 1 and memory'-CD45RO 1 T-cell subsets from patients versus controls. Similar results were obtained by ELISA testing supernatants from mitogen-stimulated, unfractionated peripheral blood mononuclear cell (PBMC) cultures. Interferon-alpha treatment was associated with a reduction in the mitogen-induced Th1 cytokine response in those patients who cleared their plasma HCV-RNA. Analysis of cytokine expression by CD4 1 T cells after HCV core antigen stimulation in a subgroup of 13 chronic hepatitis C patients demonstrated no cytokine response in 74% of these patients and an IFN-g-restricted response in 26%. Finally, no Th2 shift was found in lipopolysaccharide-stimulated monocytes. These data indicate that a Th1 to Th2 shift does not occur in chronic hepatitis C.