Subnormal rise of erythropoietin in patients receiving interferon and ribavirin combination therapy for hepatitis C.

Objectives: 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.

Conclusion: There is a subnormal rise of erythropoietin after interferon-ribavirin combination therapy for hepatitis C.