Evidence for a deficiency of interferon response in mononuclear cells from hepatitis C viremic patients

Background/Aims: The pathophysiology of chronic hepatitis C and the mechanisms of resistance to interferon α are poorly understood. The aim of this work was to assess the influence of HCV infection and the viral genotype on lymphocyte production of 2′,5′ oligo-adenylate synthetase activity and monocyte production of TNFα and IL1β. Methods: Mononuclear cells from 50 consecutive patients were studied after 6 months of interferon treatment. Patients with persistent viremia (PCR-positive, elevated ALT, n=39) were compared with the PCR-negative patients with normal ALT activity (n=11) of similar age and sex ratio. Results: Cells from the viremic patients showed lower basal and stimulated 2′,5′ oligo-adenylate synthetase activity, and a lower in vitro response capacity to human recombinant interferon. In contrast, no difference was observed in basal and stimulated TNFα or IL1β production between the two groups. In the PCR-positive patients the viral genotype had no significant influence on the response of mononuclear cells to interferon or endotoxin. Conclusions: These results show that the presence of HCV in blood is associated with an elective defect in interferon system activation, independently of the viral genotype.