0% of the anticipated dose. In another phase III study in Japan for patients who had not achieved SVR to prior IFN therapy, dose reduction of RBV was required due to anemia in 98.6% of the patients. In comparison to these reports, although our study did not include a control (non-EPO) group, patients who required RBV dose reduction due to anemia were 13.6% (3/22) and the total RBV dose was 97.5% of the anticipated amount, which
indicated that EPO administration was apparently successful for preventing RBV dose reduction. Inosine triphosphatase SNP selleckchem has been identified as a marker for susceptibility to anemia in patients who receive PEG IFN/RBV therapy. The mechanism of anemia is hypothesized to occur due to accumulation of RBV triphosphate in red blood cells inducing oxidative stress that results in hemolysis. ITPA, the substrate for ITPase, which also accumulates in red blood cells, may prevent RBV conversion to the triphosphate form. ITPase deficiency is considered to be protective against RBV-induced anemia. Here, we show that the CC genotype of ITPA revealed significantly rapid progression of anemia during the early phase in agreement with the case of PEG IFN/RBV combination therapy. Both the CC and non-CC groups, however,
seemed to show no further Hb decline after administration of EPO, and whereas the CC genotype is more prone to develop anemia, the Hb levels in the two groups became comparable probably because of the higher total EPO dose used for patients of the CC genotype. These findings indicated that EPO could control the RBV-induced check details anemia regardless of the ITPA genotype. We next compared the Hb decline of the selleck chemicals llc patients
given 1500 mg and 2250 mg in each ITPA group to investigate the effect of TVR on Hb decline. TVR has been shown to increase the incidence of RBV-induced anemia. In the non-CC group, the changes in Hb concentration were very similar for patients dosed with 1500 mg and 2250 mg. On the other hand, in the CC group, after week 3, the Hb level tended to be lower in the 2250-mg dosed patients. We assume that augmentation of the hemolytic effect of RBV by TVR may not be enough to result in a difference of Hb decline in the non-CC patients, who have the protective ITPA allele against RBV-induced anemia. In the CC group, however, because the patients were more susceptible, the higher dose of TVR might more strongly induce hemolysis. Because the number of patients was very small, it may reflect individual variability and further investigation with a large number of patients is needed to clarify this. Ribavirin is the key drug in the current IFN therapy to achieve SVR. In patients with genotype 1 and high viral load, the SVR rate of PEG IFN/RBV combination therapy is approximately 50%, while without RBV, it is approximately 20%.