It is important we can predict RBV induced anemia, and various predictive normally factors have been proposed. However, it is still difficult to predict the risk of hemolysis before the administration of RBV (21). Recently, several related studies have been conducted. In particular, the GWAS study on HCV infection identified two host genetic SNPs; one in the IL28B gene and the other is the ITPA gene. The former was found to be strongly associated with response to treatment for chronic genotype 1 HCV infections, whereas the latter was found to predict RBV induced anemia (10). ITPA gene encodes a protein that cleaves inosine triphosphate (ITP). However, the precise cellular function of ITPA has not been elucidated (22).

As mentioned above, the GWAS study identified two genetic variants in chromosome 20, namely, rs1127354 (a missense variant in exon2) and rs7270101 (a splice altering SNP). According to the study, these variants are strongly and independently associated with a reduction in Hgb during early PEG-IFN plus RBV treatment in CHC (10, 11). In our study, a functional SNP in ITPA, rs1127354, was found to be strongly associated with RBV induced anemia among 133 Korean patients (Fig. 2). Of these 133 patients, 108 possessed the RBV-sensitive CC genotype and 25 the RBV-resistant CA/AA genotype, which concur with the results of Western studies (10). However, in contrast to western studies, all Koreans enrolled were monoallelic at rs7270101 and possessed the AA genotype, which is similar to that found in Japan (23, 24).

According to previous studies, polymorphisms of the ITPA gene were associated with RBV-induced anemia in HCV genotype 1 (10). In our study, however, ITPA variant was not associated with time dependent Hgb decline in HCV genotype 1. The main cause of this result was probably because single center study conducted in small number of patients. In our multivariate analysis of anemia after 12 weeks of treatment, gender and rs1127354 were found to be independently associated with RBV induced anemia (Table 3), which suggested that rs1127354 might be a useful predictive marker of RBV induced anemia. According to previous studies, RBV dose reduction due to anemia in patients treated with PEG-IFN plus RBV is influenced by ITPA variants (11). In the present study, RBV dose was reduced more in group A than in group B during first 12 weeks of treatment (36% vs 14%, P=0.

042). Remarkably, despite its protective effect against anemia and less need for RBV dose reduction, multivariate analysis revealed that rs1127354 was not significantly associated with virological response. It is widely recognized that age and IL28B (rs8099917) are associated with SVR (Table 3), and in patients with anemia, it can be inferred that RBV dose reduction could decrease treatment efficacy. However, according Anacetrapib to previous studies, the reason of this discrepancy between RBV dose reduction and SVR is controversial (8, 11).