title: Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Lotte G
authors: LG
authors: Van Vlerken
authors: Hanneke
authors: H
authors: Van Soest
authors: Mart P
authors: MP
authors: Janssen
authors: Greet J
authors: GJ
authors: Boland
authors: Joost P H
authors: JP
authors: Drenth
authors: David M
authors: DM
authors: Burger
authors: Peter D
authors: PD
authors: Siersema
authors: Karel J
authors: KJ
authors: Van Erpecum
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000740:Anemia / Q000097:blood / Q000139:chemically induced*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects* / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D004921:Erythropoietin; D011092:Polyethylene Glycols; D012254:Ribavirin; D003404:Creatinine; C417083:peginterferon alfa-2b