Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment

Eur J Gastroenterol Hepatol. 2010 Nov;22(11):1308-15. doi: 10.1097/MEG.0b013e32833e784d.

Abstract

Background: During the treatment of hepatitis C, anaemia may necessitate pegylated-interferon and ribavirin dose reductions with reduced sustained viral response rates. Although erythropoietic growth factors are frequently used to improve anaemia, it is controversial whether endogenous erythropoietic response is insufficient under these circumstances. We aimed to identify risk factors for more pronounced anaemia and to evaluate endogenous erythropoietic response during antiviral therapy.

Methods: One hundred and forty-five naive chronic hepatitis C patients on pegylated-interferon-ribavirin treatment were evaluated for haemoglobin, haematocrit, serum ribavirin and erythropoietin levels.

Results: About 99% of patients developed anaemia, with maximal decrease in haemoglobin of 2.5 ± 1.0 mmol/l (range 0.3-5.5 mmol/l). Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia. Serum erythropoietin levels increased from median 12 IU/l (range 4-63 IU/l) at baseline to 41 IU/l (range 12-683 IU/l) after 12 weeks of therapy and to 43 IU/l (range 7-3238 IU/l) at week 24 (P<0.001). Erythropoietin levels at baseline, week 12 and week 24 negatively correlated with haematocrit. The erythropoietic response to anaemia in our study population was significantly different from the normal human response to anaemia.

Conclusion: Older age, lower baseline creatinine clearance, higher baseline haemoglobin, more pronounced haemoglobin decrease after 2 weeks and higher week 24 serum ribavirin concentrations were independent risk factors for more pronounced anaemia during antiviral therapy. Endogenous erythropoietin production is suboptimal during antiviral therapy, supporting use of erythropoietic growth factors.

Trial registration: ClinicalTrials.gov NCT00146016.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Anemia / blood
  • Anemia / chemically induced*
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / blood
  • Biomarkers / blood
  • Creatinine / blood
  • Double-Blind Method
  • Drug Therapy, Combination
  • Erythropoietin / blood*
  • Female
  • Hematocrit
  • Hemoglobins / metabolism
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / adverse effects*
  • Linear Models
  • Logistic Models
  • Male
  • Middle Aged
  • Polyethylene Glycols / adverse effects*
  • RNA, Viral / blood
  • Recombinant Proteins
  • Ribavirin / adverse effects*
  • Ribavirin / blood
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Biomarkers
  • Hemoglobins
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Erythropoietin
  • Polyethylene Glycols
  • Ribavirin
  • Creatinine
  • peginterferon alfa-2b

Associated data

  • ClinicalTrials.gov/NCT00146016