GLUTATHIONE DEPLETION IN CHRONIC HEPATITIS-C

Reduced glutathione (GSH) protects against oxidative stress and may al so influence gene expression and viral replication. Hepatitis C virus (HCV) is a positive-stranded RNA virus which replicates in the liver a nd lymphoid cells through a negative RNA intermediate. The possible ro le of GSH changes in the pathogenesis of this infection has not yet be en established. We have determined GSH concentrations in plasma and in peripheral mononuclear cells from 100 patients with chronic hepatitis C and in 26 normal individuals. In untreated patients (n = 46) GSH in plasma and in lymphoid cells was markedly decreased as compared with controls (P < 0.01). Patients who normalized transaminases during inte rferon therapy (n = 25) showed significantly higher levels of GSH in p lasma and in mononuclear cells than untreated patients or interferon-r esistant patients (n = 29) (P < 0.01). Both plasma and intralymphocyti c GSH correlated inversely with transaminase values. In all untreated patients both the (+) and the (-) HCV-RNA strands were detected in lym phoid cells and this was associated with low intralymphocytic GSH. In patients who responded to interferon treatment the near-normalization of intralymphocytic GSH was associated with the complete clearance of the virus in 78% of the cell samples. Thus, in chronic hepatitis C the re is a systemic depletion of glutathione that appears to be related t o the activity of the disease.