Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment.
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.
Van Vlerken
Lotte G
LG
Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
Van Soest
Hanneke
H
Janssen
Mart P
MP
Boland
Greet J
GJ
Drenth
Joost P H
JP
Burger
David M
DM
Siersema
Peter D
PD
Van Erpecum
Karel J
KJ
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
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