Association of ITPA Polymorphism with Outcomes of Peginterferon-α Plus Ribavirin Combination Therapy

Background and Aims: Hematological abnormalities during hepatitis C Virus (HCV) combination therapy with pegylated interferon a and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to analyzed the association between inosine triphosphatase (ITPA (rs1 127354) genotypes and early virological response (EVR) rates in peginterferon (Peg-IFN)α + ribavirin (RBV) treatment. Methods: Patients who underwent Peg-IFNα + RBV combination therapy were enrolled (n=149). Variation in hemoglobin levels during therapy, cumulative reduction of RBV dose, frequency of treatment withdrawal, and EVR rates were investigated in each ITPA genotype. Results: In patients with ITPA CC genotype, hemoglobin decline was significantly greater and the percentage of patients in whom total RBV dose was reduced significantly higher compared with CA genotype. However, EVR rates were equivalent between CC and CA genotypes. Conclusion: ITPA CC genotype was a disadvantageous factor for Peg-IFNα + RBV treatment in relation to completion rates and RBV dose. However, CC genotype was not inferior to CA genotype for EVR rates.