We found no difference in virological outcomes when these 14 patients check details were excluded from analysis. Given that both studies demonstrated similar relationships between haemoglobin decline

and SVR, it seems unlikely that erythropoietin use per se is the major factor contributing to the increased SVR rates seen in patients with significant therapy-induced hemoglobin decline. However, greater utilization of erythropoietin, particularly among those patients with hemoglobin declines >30 g/L during the initial 4 weeks of therapy, may have improved SVR rates in the CHARIOT study. Specific studies are required to examine the role of erythropoietin in this group of patients with a rapid hemoglobin decline. We identified several patient characteristics that were associated

with on-treatment development of anemia. Anemia was more likely in women with lower body weight, older age, lower creatinine clearance, and lower baseline hemoglobin concentrations, white cell counts, and platelet counts (Table 1). Those who developed a hemoglobin decline >30 g/L were more likely to be female and older with lower body weight, but with a higher baseline hemoglobin level than those who never developed a similar fall in hemoglobin concentration (data not shown). When analyzed by time to first occurrence of a hemoglobin decline >30 g/L, we observed similar changes, because older patients with a lower body weight, lower creatinine BMS-354825 clinical trial clearance, and higher baseline hemoglobin level were more likely to develop a hemoglobin decline >30 g/L (Table 4). These findings are consistent with previous studies that have identified similar clinical risk factors for developing ribavirin-induced anemia.5-7 A predictive pharmacokinetic model that incorporates some of these

factors has been Non-specific serine/threonine protein kinase reported,8 but the use of patient characteristics to predict ribavirin-associated hematological changes has not gained widespread clinical use. The precise mechanisms underlying the higher SVR rates in patients with a decline in hemoglobin remain unclear. Given the well-known hemolytic effects of ribavirin, it would be reasonable to assume that this observation is related to an individual pharmacokinetic response to that drug. Pharmacokinetic studies have shown that ribavirin reaches steady state plasma concentrations after 3-12 weeks of continued dosing and that ribavirin clearance is determined principally by body weight and renal function.9 A study of 380 Caucasian male HCV patients of mixed genotypes with plasma sampled at steady state (weeks 8-48 of therapy) reported that lean body weight was the most important covariate affecting ribavirin clearance, which increased linearly with body weight.