The possible role of zinc and metallothionein in the liver on the therapeutic effect of IFN-alpha to hepatitis C patients.

Abstract

We have studies zinc deficiency in hepatitis C patients (complete responder [CR] 22, nonresponder [NR] 25) with relation to the therapeutic effect of interferon-alpha (IFN-alpha). Circadian variations in serum zinc levels were high in the morning (basal level) and then gradually decreased during the day in both chronic hepatitis C patients and healthy controls. Basal zinc levels in serum were significantly lower in chronic hepatitis C patients (73 +/- 3 micrograms/dL, n = 12) than in controls (93 +/- 5 micrograms/dL). An injection of 10 MU of IFN-alpha to hepatitis C patients augmented the serum zinc reductions, up to 40% in 8 h. Serum cortisol levels were significantly elevated 8 h (25.6 +/- 2.3 micrograms/dL) after IFN-alpha dose. Forty-seven chronic hepatitis C patients were treated with IFN-alpha for 24 wk, and serum zinc and copper levels were determined 12 and 24 wk during and after the completion of IFN-alpha therapy. Serum zinc levels and zinc/copper ratio were higher in CRs than in NRs to IFN therapy at each time-point. Hepatic metallothionein staining became prominent after IFN therapy in most of CRs, whereas it diminished NRs. These data suggest that nutritional status of zinc influences the effect of IFN on hepatitis C patients.