RBV induced anemia was defined as a decline of more than 3 g/dL of Hgb level from before anti-viral treatment or less than 10 g/dL of Hgb level during anti-viral treatment (10, 11). Twenty-one (19%) patients in group A and 1 (4%) patient in group B were diagnosed with RBV induced selleck anemia after 4 weeks of anti-viral treatment, 45 (42%) and 2 (8%) after 8 weeks, and 54 (50%) and 4 (16%) after 12 weeks. Mean Hgb levels were 12.2, 11.8, and 11.5 g/dL after 4, 8, and 12 weeks of antiviral treatments in group A and 14, 13.2, and 12.9 g/dL in group B (P=0.001, 0.036, 0.036). Fig. 2 compares decreases in mean Hgb values in the two groups. Additionally, we conducted subgroup analysis between group A and B of HCV genotype 1. Mean Hgb levels were 12.4, 11.7, and 11.

3 after 4, 8 and 12 weeks of antiviral treatment in group A of HCV genotype 1 and 13.9, 13.3, and 12.7 in group B (P=0.206, 0.601, 0.155). Fig. 2 Time dependent hemoglobin declines by ITPA genotype. Modification of RBV dose after 4, 8, and 12 weeks of treatment by ITPA genotype RBV dose modifications were as followings; a reduction of 200 mg when the Hgb level was<10 g/dL and stopped when the Hgb level was<8 g/dL. Eight patients discontinued PEG-IFN and RBV treatment because of side effects, such as, a loss of appetite, dizziness, or depression, and therefore, the analysis of RBV dose modification included 125 patients. During the first 12 weeks of anti viral treatment, RBV dose reduction (>200 mg) was performed in 40 patients. RBV dose reduction was started earlier in 16 (16%) patients in group A than in the 3 (14%) patients in group B.

During the first 12 weeks of anti-viral treatment, the rate of RBV dose reduction increased steadily in group A, whereas no further RBV dose reduction occurred after 4 weeks in group B. RBV dose reductions after 12 weeks of treatment were performed in 37 patients (36%) in group A and in 3 patients (14%) in group B (P=0.042) (Fig. 3). Fig. 3 Cumulative percentages of patients requiring ribavirin dose reduction after 4, 8, and 12 weeks of treatment by ITPA genotype. Prognostic factors influencing decreases in Hgb level To investigate the influences of potential prognostic factors on RBV induced anemia, 6 factors (gender, age>60 yr, BMI>23 kg/m2, liver cirrhosis, initial Hgb level [<14 g/dL], and CC genotype of the ITPA variant) were examined individually by univariate analysis.

To identify independent prognostic factors, stepwise forward multiple logistic regression analysis was performed. Multivariate analysis showed that only a male gender and the CC genotype positively influenced RBV induced anemia (Table 2). Table 2 Univariate and multivariate analyses of host and viral factors associated with anemia after 12 weeks of treatment ITPA and the IL28B genotype Anacetrapib and virologic response SVR was achieved in 67.