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

Hepatology. 2000 Apr;31(4):997-1004. doi: 10.1053/he.2000.5789.


The antiviral drug ribavirin (RBV) is widely used in combination with interferon (IFN) in the treatment of chronic hepatitis C virus (HCV) infection. A major side effect of RBV is a reversible hemolytic anemia. We have evaluated the in vitro effects of RBV on erythrocyte adenosine triphosphate (ATP) content and on hexosemonophosphate shunt (HMS). The ATP levels were significantly decreased in the presence of RBV and the HMS was increased, suggesting the presence of red cell susceptibility to oxidation. In vivo, we have studied the hematologic effects of treatment with RBV alone or in combination with IFN in 11 patients with chronic hepatitis C: 6 were treated with RBV (1,000-1,200 mg/d) and 5 were treated with a combination of RBV 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 significant reduction in hemoglobin levels (steady state level at day 45) and a marked increase in absolute reticulocyte counts. Erythrocyte Na-K pump activity was significantly diminished, whereas K-Cl cotransport and its dithiotreitol-sensitive fraction, malondialdehyde and methemoglobin levels were significantly increased. RBV-treated patients showed an increase in aggregated band 3, which was associated with a significantly increased binding of autologous antibodies and complement C3 fragments indicating an erithrophagocytic removal by reticuloendothelial system.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / blood
  • Adult
  • Anemia, Hemolytic / blood
  • Anemia, Hemolytic / chemically induced*
  • Anion Exchange Protein 1, Erythrocyte / metabolism
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Carrier Proteins / blood
  • Complement C3 / metabolism
  • Erythrocyte Membrane* / immunology
  • Female
  • Hemoglobins / metabolism
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Immunoglobulin G / blood
  • Interferons / therapeutic use
  • Male
  • Middle Aged
  • Oxidative Stress*
  • Reticulocyte Count
  • Ribavirin / adverse effects*
  • Ribavirin / therapeutic use
  • Sodium-Potassium-Exchanging ATPase / blood
  • Symporters*


  • Anion Exchange Protein 1, Erythrocyte
  • Antiviral Agents
  • Carrier Proteins
  • Complement C3
  • Hemoglobins
  • Immunoglobulin G
  • Symporters
  • potassium-chloride symporters
  • Ribavirin
  • Adenosine Triphosphate
  • Interferons
  • Sodium-Potassium-Exchanging ATPase