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Effects of ITPA polymorphism on decrease of hemoglobin during simeprevir, peg-interferon, and ribavirin combination
Kei Morio1, Michio Imamura1, Yoshiiku Kawakami1
1Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Summary
ITPA gene variations impact anemia and ribavirin dose reduction in hepatitis C patients undergoing triple therapy. Close monitoring is crucial, especially for those with the ITPA genotype CC.
Area of Science:
- Hepatology
- Pharmacogenetics
- Viral Hepatitis
Background:
- Polymorphisms in the inositol triphosphate A (ITPA) gene are known to affect anemia during peg-interferon (PEG-IFN) and ribavirin (RBV) therapy.
- The impact of ITPA polymorphisms on outcomes during triple therapy including simeprevir, PEG-IFN, and RBV remains less understood.
Purpose of the Study:
- To investigate the influence of ITPA gene polymorphisms on hemoglobin levels and RBV dose reduction in patients with chronic hepatitis C genotype 1 treated with simeprevir, PEG-IFN, and RBV.
- To identify factors associated with treatment outcomes in this patient cohort.
Main Methods:
- Genotyping of ITPA (rs1127354) and IFNL4 (ss469415590) polymorphisms using the Invader assay in 212 patients.
- Assessment of hemoglobin levels and RBV dose reduction in patients receiving simeprevir plus PEG-IFN/RBV triple therapy.
- Stepwise multivariate regression analysis to determine factors associated with treatment outcomes.
Main Results:
- Hemoglobin reduction was comparable between triple therapy and PEG-IFN/RBV therapy alone.
- Patients with ITPA genotype CC experienced faster and greater hemoglobin decreases and a higher incidence of RBV dose reduction compared to CA/AA genotypes.
- Multivariate analysis identified IFNL4 TT/TT genotype, treatment history, and treatment completion as significant predictors of outcome, but not the ITPA SNP genotype.
Conclusions:
- ITPA polymorphism significantly affects hemoglobin levels and the need for RBV dose reduction during simeprevir triple therapy.
- Anemia monitoring is essential during treatment, particularly for ITPA genotype CC patients.
- While ITPA genotype influences specific aspects of treatment response, IFNL4 genotype and treatment history appear more strongly associated with overall treatment outcomes.
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