Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients

Ribavirin (RBV)-induced anemia is a serious side effect of pegylated interferon (PEG-IFN) plus RBV therapy which is the standard care most effective for hepatitis C virus (HCV) infection. In the present study, we investigated the association of inosine triphosphate pyrophosphatase (ITPA) genotypes with RBV-induced hemoglobin (Hb) reduction in HCV patients treated with PEG-IFN/RBV therapy. The genotypes of the ITPA rs1127354 single nucleotide polymorphism were determined in 179 patients with HCV infection. Among them, 52 patients were treated with PEG-IFN/RBV. The frequency of the ITPA major allele (CC) was 76.3% and that of the minor allele (CA and AA) was 23.7%. A rapid decrease in Hb levels during the initial 4 weeks was observed in patients with the ITPA major allele (CC), but not in patients with the ITPA minor allele (C/A and AA). Hb levels at 4 weeks were significantly lower in patients with the ITPA major allele than the levels in patients with the minor allele. Out of the 41 patients, 6 (14.6%) with ITPA major allele had Hb levels <10 g/dl and 11 patients (26.8%) had a decline in Hb of >3 g/dl. None of the patients with the ITPA minor allele had such data. There were no significant differences in virological responses of HCV-RNA between patients with the ITPA major allele and those with the minor allele. In conclusion, the ITPA genotypes may be a useful marker for prediction of RBV-induced anemia.