GLUTATHIONE DEPLETION IN CHRONIC HEPATITIS-C

Reduced glutathione (GSH) protects against oxidative stress and may also influence gene expression and viral replication. Hepatitis C virus (HCV) is a positive-stranded RNA virus which replicates in the liver and lymphoid cells through a negative RNA intermediate. The possible role of GSH changes in the pathogenesis of this infection has not yet been 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 interferon therapy (n = 25) showed significantly higher levels of GSH in plasma and in mononuclear cells than untreated patients or interferon-resistant patients (n = 29) (P < 0.01). Both plasma and intralymphocytic GSH correlated inversely with transaminase values. In all untreated patients both the (+) and the (-) HCV-RNA strands were detected in lymphoid 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 there is a systemic depletion of glutathione that appears to be related to the activity of the disease.