68 mg/dL at baseline to 1.17 mg/dL at week 10. Another patient (no. 20) required TVR discontinuation at week 9 and RBV dose reduction at week 11 due to creatinine elevation from 0.78 mg/dL at baseline to 1.16 mg/dL. The skin disorder as an adverse event developed in 10 patients: nine were grade 1 and one was grade 2. All of them were controllable by using steroid ointment. Ribavirin has been

shown to induce hemolytic anemia. HER2 inhibitor Triple therapy (i.e. addition of TVR to RBV) often accelerates RBV-induced anemia requiring subsequent dose reduction of RBV in a majority of patients. In the present study, we focused on the effect of EPO during the triple therapy phase. Mean Hb decline is shown in Figure 1. Significant Hb decline was seen after 2 weeks of treatment. Further Hb decline was detected at week 3, and 16 of 22 patients were given EPO administration. After week 4, the decline of mean Hb concentration became modest probably due to the effect of EPO. The decline of mean Hb concentration was 2.5 g/dL, 2.9 g/dL and 3.0 g/dL at

weeks 4, 8 and 12, respectively. Every patient was given EPO injection twice or more during the triple therapy phase. For three patients (nos. 9, 15 and 18) receiving 1500 mg of TVR daily, the RBV dose was reduced by 200 mg/day at weeks 11, 11 and 12, respectively, due to the occurrence of anemia (Hb, <10 g/dL). Dose reduction of TVR and RBV due to anemia Navitoclax manufacturer was not required in the other 19 patients. Collectively, in this study, five patients (nos. 6, 9, 15, 18 and 20) had to reduce or stop RBV. The other 17 patients completed the treatment during the triple therapy phase without RBV reduction. All patients who received EPO administration experienced no adverse events attributable to Sclareol EPO. The average total EPO dose used in the 12 weeks for the 20 patients who could continue TVR during the triple therapy phase was 110 400 IU. The ITPA genotype at rs1127354 was CC for

14 patients. All of the eight non-CC patients had the CA genotype. Because ITPA is considered to be associated with RBV-induced anemia by modifying hemolysis, the degree of anemia between the two groups was compared. Early decline of Hb concentration was more prominent in the CC group (Fig. 2) in good agreement with previous reports. At week 3, significant Hb decline was observed in the CC group and 92.9% (13/14) of the patients were given EPO administration. After week 4, no further decline of Hb was detected probably because of the hematopoietic effect of EPO. On the other hand, the non-CC genotype group showed a slow Hb decline. At week 6, EPO was given to 75% (6/8) of the patients and the Hb level was not changed thereafter. Comparing the two groups, before week 6, the decline of Hb was rapid and the rate of patients given EPO administration was higher for the CC group.