EVIDENCE FOR A DEFICIENCY OF INTERFERON RESPONSE IN MONONUCLEAR-CELLSFROM HEPATITIS-C VIREMIC PATIENTS

Background/Aims: The pathophysiology of chronic hepatitis C and the me chanisms of resistance to interferon alpha 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 synth etase activity and monocyte production of TNF alpha and IL1 beta. Meth ods: Mononuclear cells from 50 consecutive patients were studied after 6 months of interferon treatment, Patients with persistent viremia (P CR-positive, elevated ALT, n=39) were compared with the PCR-negative p atients with normal ALT activity (n=11) of similar age and sex ratio, Results: Cells from the viremic patients showed lower basal and stimul ated 2',5' oligo-adenylate synthetase activity, and a lower in vitro r esponse capacity to human recombinant interferon, In contrast, no diff erence was observed in basal and stimulated TNF alpha or IL1 beta prod uction between the two groups, In the PCR-positive patients the viral genotype had no significant influence on the response of mononuclear c ells 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.