Hemolytic anemia induced by ribavirin therapy in patients with chronic hepatitis C virus infection: Role of membrane oxidative damage

The antiviral drug ribavirin (RBV) is widely used in combination with inter feron (IFN) in the treatment of chronic hepatitis C virus (HCV) infection. A major side effect of REV is a reversible hemolytic anemia. We have evalua ted the in vitro effects of REV on erythrocyte adenosine triphosphate (ATP) content and on hexosemonophosphate shunt (HMS), The ATP levels were signif icantly decreased in the presence of REV and the HMS was increased, suggest ing the presence of red cell susceptibility to oxidation, In vivo, we have studied the hematologic effects of treatment with REV alone or in combinati on with IFN in 11 patients with chronic hepatitis C: 6 were treated with RE V (1,000-1,200 mg/d) and 5 were treated with a combination of REV and IFN ( 5 million U thrice weekly). Patients were studied at semi-monthly intervals from 0 to day 60 of therapy. Both treatments were associated with a signif icant reduction in hemoglobin levels (steady state level at day 45) and a m arked increase in absolute reticulocyte counts. Erythrocyte Na-K pump activ ity was significantly diminished, whereas K-Cl cotransport and its dithiotr eitol-sensitive fraction, malondialdehyde and methemoglobin levels were sig nificantly increased. REV-treated patients showed an increase in aggregated band 3, which was associated with a significantly increased binding of aut ologous antibodies and complement C3 fragments indicating an erithrophagocy tic removal by reticuloendothelial system.