N-ACETYL CYSTEINE ENHANCES THE RESPONSE TO INTERFERON-ALPHA IN CHRONIC HEPATITIS-C - A PILOT-STUDY

Hepatitis C virus (HCV) is an RNA virus that replicates in both the li ver and lymphoid cells. Interferon-alpha (IFN-alpha) is a useful treat ment of chronic hepatitis C (CHC) although resistance to this drug occ urs frequently. The mechanisms underlying resistance to IFN remain unk nown. In this work, we have measured the levels of glutathione in plas ma and peripheral lymphoid cells from 15 healthy controls and 24 CHC p atients, 10 of whom were without treatment and 14 showed high serum al anine aminotransferase (ALT) values despite therapy with lymphoblastoi d IFN for more than 4 months. In all patients, glutathione levels in p lasma and in mononuclear cells were depressed in comparison to control s. In IFN-unresponsive patients, the addition of 600 mg tid of oral N- acetyl cysteine (NAC), a glutathione precursor, resulted in a steady d ecrease of ALT values in all patients, with complete normalization in 41% of cases after 5-6 months of combined therapy. Administration of N AC alone for 1 month was without effect in the 10 patients that were n ot receiving IFN. Supplementation of IFN with NAC induced a near norma lization of intralymphocytic glutathione, but plasma levels were only moderately increased. HCV replication was markedly inhibited in lympho cytes and viremia was cleared in one of the 8 patients tested. In conc lusion, NAC enhances the response to IFN in CHC. Controlled studies ar e needed to ascertain whether antioxidant therapy might act in synergy with IFN in chronic viral hepatitis.