Clinical and basal aspects of anemia during antiviral therapy for hepatitis C.
OBJECTIVE
Anemia is a major side effect of combination therapy for chronic hepatitis C. In this study, severity, potential risk factors for and potential underlying mechanisms of anemia were evaluated.


METHODS
44 chronic hepatitis C patients on interferon-ribavirin treatment were included. Anemia-related parameters were measured before and during treatment. Potential changes in membrane phospholipids composition of erythrocytes of patients on anti-viral treatment and potentially increased erythrocyte susceptibility to osmotic or bile salt induced stress were explored.


RESULTS
Anemia was almost universal during treatment, with evidence of hemolysis. Decrease of Hb after six months of therapy was 2.1 +/- 0.1 mmol/L (range -0.6-4.1). Higher pre-treatment Hb, highest ribavirin dose (15-17.5 mg/kg) and lower pre-treatment platelet level were independent risk factors for decrease of Hb. Serum erythropoietin levels increased during treatment with negative correlation to Hb levels at week 12 (r = -0.70, p = 0.002) and 24 (r = -0.72, p = 0.002). Erythrocyte membrane phospholipid composition did not differ between anemic patients and healthy controls. Also, resistance to osmotic or bile salt induced stress was normal in anemic patients. Phosphatidylserine exposure at the outer membrane leaflet did not change upon 24 hrs ex vivo incubation with pharmacological ribavirin concentration.


CONCLUSIONS
Anemia is almost universal during anti-HCV treatment. The extent of anemia correlates with pre-treatment levels of thrombocytes and Hb and with high ribavirin dosing. Although we found hemolysis as contributing factor, our data do not indicate that altered membrane phospholipids composition is an important factor in pathogenesis of anemia.
van Soest
Hanneke
H
Depts. of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Renooij
Willem
W
van Erpecum
Karel J
KJ
D000328:Adult; D000368:Aged; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use; D000740:Anemia / Q000097:blood* / Q000139:chemically induced*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004910:Erythrocyte Membrane / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000378:metabolism; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000378:metabolism; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use
D000998:Antiviral Agents; D001647:Bile Acids and Salts; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D010743:Phospholipids; D011994:Recombinant Proteins; D004921:Erythropoietin; D011092:Polyethylene Glycols; D012254:Ribavirin; D000547:Amantadine; C100416:peginterferon alfa-2a