[1]China-Japan Union Hospital, Jilin University, Changchun, China.
Background: This prospective study investigated the relationship between two inosine triphosphatase (ITPA) polymorphisms (rs7270101 and rs1127354) and the efficacy of ribavirin-based antiviral therapy in hepatitis C virus (HCV)-infected Chinese patients. Methods: A total of 906 patients diagnosed with chronic hepatitis C receiving pegylated interferon (PEG-IFN) plus ribavirin combination therapy between January 2011 and January 2014 from five hepatitis centers in Northeast China were enrolled. The patients were divided into genotype 1 and non-genotype 1 groups according to the genotype of infected HCV. ITPA single nucleotide polymorphism (SNP) genotyping was performed for all patients. Ribavirin-induced hemolytic anemia and virological response (VR) were monitored during treatment and follow-up. The relationship between the ITPA SNPs and hemolytic anemia and VR was analyzed. Multivariate regression analysis was used to analyze the predictors for sustained VR (SVR). Result: IPTA rs7270101 variants were not detected. IPTA rs1127354 variants were detected and showed no difference between the genotype 1 and non-genotype 1 groups. IPTA rs1127354 genotype CC was related to a higher incidence of ribavirin-induced hemolytic anemia. The percentage of patients with rs1127354 CC who received more than 80% of the planned ribavirin dose was lower than that of patients with rs1127354 non-CC. For patients who received more than 80% of the planned ribavirin dose, rs1127354 variants and related ITPase were related to better SVR. rs1127354 non-CC in the non-genotype 1 group showed better VR from Week 12 post treatment, whereas rs1127354 non-CC in the genotype 1 group showed better VR from Week 48 post treatment. Multivariate analysis showed that IPTA rs1127354 non-genotype CC, HCV genotype, a baseline HCV RNA level less than 4 × 10(5) IU/mL, IL-28B rs12979860 genotype CC, and low liver fibrosis (FibroScan 0-2) were independent predictors for SVR during PEG-IFN plus ribavirin combination therapy. Conclusion: IPTA rs1127354 variants and related ITPase were not only related with ribavirin-induced hemolytic anemia but also directly affected the SVR to PEG-IFN plus ribavirin combination therapy in Chinese HCV-infected patients.
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