Many novel IFN-free antiviral regimens for HCV are now under clinical investigation.[23, 24] Some of these include RBV in combination with one or two direct-acting antiviral agents.[25, 26] RBV will remain a key drug for the treatment of chronic HCV infection in the forthcoming era of oral combination therapy. Therefore, it is critical to

establish effective strategies for managing RBV-induced anemia, including the use of erythropoietin, Erlotinib clinical trial and determine its optimal dose for Japanese patients. The mechanism of RBV-induced hemolytic anemia is not completely understood. In erythrocytes, RBV is converted into mono-, bi- and finally triphosphate forms. The active forms of RBV accumulate in red blood cells because of a lack of phosphatases required to hydrolyze them, probably leading to hemolysis. Fellay et al.[27] show that genetic variants near the inosine triphosphatase (ITPA) gene protect

against hemolytic anemia in HCV-infected patients receiving RBV. One possible Adriamycin explanation for this finding is that ITPA deficiency caused by the ITPA gene variation leads to an accumulation of inosine triphosphate, which can compete with the triphosphate form of RBV in red blood cells, thereby protecting cells from the lytic effects of the active form. Ochi et al.[28] report that 75.1% of Japanese patients with chronic hepatitis C are homozygous for the major allele CC at rs1127354. All three patients in the present report had the ITPA major type associated with treatment-induced anemia (Table 1). Erythrocyte-stimulating agents epoetin-α and

epoetin-β are the two forms of human recombinant erythropoietin; both are synthesized in Chinese hamster ovary cells, which are commonly used to treat anemia in chronic kidney disease.[29] Although there are some differences in the glycosylation of the polypeptide in post-translational processing, epoetin-α and epoetin-β essentially have the same clinical efficacy. A higher dose of erythropoietin is required 上海皓元 to maintain hemoglobin levels in chronic hepatitis C patients with preserved production of endogenous erythropoietin than in patients with chronic kidney disease. Most clinical studies conducted in the USA used epoetin-α at a dose of 40 000–60 000 IU once weekly. In their preliminary dose-finding study, Kanai et al.[30] report that 24 000–36 000 IU epoetin-β appears to be the optimal dose for Japanese patients with chronic HCV infection. Accordingly, we adopted 24 000 IU epoetin-β. Biweekly dosing of erythropoietin is commonly used in clinical practice to treat anemia in chronic kidney disease as a maintenance therapy if hemoglobin level is elevated by weekly dosing. Therefore, we administrated epoetin-β weekly six times followed by biweekly three times. No significant reductions in the dose of RBV were required after initiation or discontinuation of the biweekly epoetin-β dosing (Fig. 3).