The Relationship Between ITPA Rs1127354 Polymorphisms And Efficacy/long-term Prognosis Of Antiviral Treatment In CHC Patients

Part 1The relationship between ITPA rs1127354 polymorphisms andefficacy of antiviral treatment in Northeast Chinese CHC patientsAims: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.Multivariate regression analysis was used to analyze the predictors for sustained VR(SVR).Results:IPTA rs7270101 variants were not detected.IPTA rs1127354 variants were detected and showed no difference between the genotype 1 and non-genotype 1groups.IPTA rs1127354 genotype CC was related to a higher incidence of ribavirin-induced hemolytic anemia.For patients who received more than 80%of the planned ribavirin dose,rs1127354 variants and related ITPase were related to better SVR.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 rs12979860genotype CC,and low liver fibrosis were independent predictors for SVR during the 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.Part 2 ITPA polymorphisms are associated with long-term prognosis after treatment with pegylated interferon and ribavirin for chronic hepatitis CAims:This prospective study investigated the relationship between two inosine triphosphatase(ITPA)polymorphisms(rs7270101 and rs1127354)and the long-term prognosis of ribavirin-based antiviral therapy in hepatitis C virus(HCV)-infected Chinese patients.Methods:A total of 635 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 and has completed 5 years of follow-up 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.HCV RNA level and Fibrosis(Fibro Scan)were monitored during treatment and a five-year follow-up.Multivariate regression analysis was used to analyze the predictors for long-term prognosis.Results:For patients who received more than 80% of the planned ribavirin dose,rs1127354 variants and related ITPase were related to better long-term virological response and improvement of liver fibrosis during a five-year follow-up.Multivariate analysis showed that low liver fibrosis,HCV non-genotype 1,a baseline HCV RNA level less than 4×105 IU/m L,IL-28 B rs12979860 genotype CC,IPTA rs1127354 non-genotype CC were independent predictors for long-term virological response,and showed that IL-28 B rs12979860 non-genotype CC,IPTA rs1127354 genotype CC and severe liver fibrosis were independent predictors for poor improvement of liver fibrosis.The total incidence of liver cancer in 5 years was 1.36%(6/442),all of which were ITPA rs1127354 genotype CC patients.Conclusion:IPTA rs1127354 variants and related ITPase were related with long-term virological response and improvement of liver fibrosis during a five-year follow-up to PEG-IFN plus ribavirin combination therapy in Chinese HCV-infected patients.