Subnormal rise of erythropoietin in patients receiving interferon and ribavirin combination therapy for hepatitis C.
OBJECTIVE
Anemia is a common complication during interferon-ribavirin therapy for hepatitis C. While normally a fall in hematocrit in results in an exponential compensatory rise in erythropoietin, such that the correlation between hematocrit and erythropoietin is sharply negative, the erythropoietin response during interferon-ribavirin combination therapy is not known.


METHODS
We measured the hematocrit and erythropoietin levels before and after about 4 weeks of interferon-ribavirin therapy for hepatitis C (n = 43), and compared their relation to the normal human response to anemia.


RESULTS
The hematocrit fell from an average pre-treatment level of 43.7 +/- 3.7% to 36.9 +/- 5 (P < 0.0001). The erythropoietin level rose from 14.5 +/- 15.1 to 58.5 +/- 94.1 units/L (P < 0.0001), indicating there was an adequate stimulus for erythropoietin release. The rise of erythropoietin was severely impaired in relation to the normal human response to a fall in hematocrit. Using the normal human response to anemia as the population line, for our population there was a significant difference in the slope of hematocrit (x) versus log10 erythropoietin (y) (-8.7 vs. -3.098 respectively, P < 0.001) and y-intercept (4.609 vs. 2.753 respectively, P < 0.001). The Bonferroni adjusted "p" value was derived to be <0.002. There was an approximate 2 log10 reduction in maximal achievable erythropoietin level in subjects exposed to interferon-ribavirin combination.


CONCLUSIONS
There is a subnormal rise of erythropoietin after interferon-ribavirin combination therapy for hepatitis C.
Trivedi
Hariprasad S
HS
Nephrology Section, Harry S. Truman Memorial Veterans' Hospital, Columbia, MO 65201, USA. trivedih@health.missouri.edu
Trivedi
Madhuri
M
D000328:Adult; D000740:Anemia / Q000139:chemically induced*; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D006400:Hematocrit; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004921:Erythropoietin; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a