2-5 As Activity in Serum and Peripheral Blood Mononuclear Cells for Chronic Active Hepatitis C and the Relationship to Clinical Outcome of Interferon Therapy

Of 49 patients with chronic hepatitis C treated by interferon (IFN), we measured 2′-5′-oligoadenylate synthetase (2-5 AS) activity in peripheral blood mononuclear cells (PBMC) and serum before and after the IFN therapy and studied the correlation with the clinical outcome. Before IFN therapy, the levels of 2-5 AS in PBMC and serum were significantly higher in patients with chronic hepatitis C than in healthy controls, though there was no correlation between the 2-5 AS activity and the clinical outcome. When PBMC were stimulated with IFN in vitro, the induced 2-5 AS activities in patients with chronic hepatitis C were almost same as those in healthy controls. Among patients infected with hepatitis C virus (HCV) genotype II which was considered relatively resistent to IFN, patients whose HCV was disappeared from serum by IFN therapy showed good induction of 2-5 AS activity by IFN in vitro, whereas patients in which serum HCV remained positive after the therapy showed poor response to IFN in vitro. The levels of 2-5 AS in PBMC 2 months after IFN therapy were still higher in patients whose HCV was continuously disappeared from serum by the therapy (complete remission) than in healthy controls. The in vitro induction of 2-5 AS in patients whose HCV in serum remained positive after the therapy was significantly lower than in patients with complete remission. The induction of 2-5 AS activity in patients to whom IFN therapy was ineffective, significantly decreased after the IFN therapy as compared with the activity measured before the therapy.Thes findings suggest that measurement of 2-5 AS activity in PBMC in vitro through IFN therapy might be useful for predicting in vivo responsibility to IFN and also knowing the change of the responsibility.