Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir †

Hepatology
Early View (Articles online in advance of print)

Fumitaka Suzuki1,*,‡, Yoshiyuki Suzuki1, Norio Akuta1, Hitomi Sezaki1, Miharu Hirakawa1, Yusuke Kawamura1, Tetsuya Hosaka1, Masahiro Kobayashi1, Satoshi Saito1, Yasuji Arase1, Kenji Ikeda1, Mariko Kobayashi2, Kazuaki Chayama3, Naoyuki Kamatani4, Yusuke Nakamura5, Yuzo Miyakawa6, Hiromitsu Kumada1

Article first published online: 18 JAN 2011
DOI: 10.1002/hep.24058
Copyright © 2011 American Association for the Study of Liver Diseases

Abstract

Polymorphisms of the inosine triphosphatase (ITPA) gene influence anemia during pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy, but their effects during triple therapy with PEG-IFN, RBV, and telaprevir are not known. Triple therapy for 12 weeks, followed by PEG-IFN and RBV for 12 weeks, was given to 49 patients with RBV-sensitive (CC at rs1127354) and 12 with RBV-resistant (CA/AA) ITPA genotypes who had been infected with hepatitis C virus (HCV) of genotype 1. Decreases in hemoglobin levels were greater in patients with CC than CA/AA genotypes at week 2 (−1.63 ± 0.92 vs. −0.48 ± 0.75 g/dL, P = 0.001) and week 4 (−3.5 ± 1.1 vs. −2.2 ± 0.96, P = 0.001), as well as at the end of treatment (−2.9 ± 1.1 vs. −2.0 ± 0.86, P = 0.013). Risk factors for hemoglobin <11.0 g/dL at week 4 were female gender, age >50 years, body mass index (BMI) <23, and CC at rs1127354 by multivariate analysis. RBV dose during the first 12 weeks was smaller in patients with CC than CA/AA genotypes (52 ± 14% vs. 65 ± 21% of the target dose, P = 0.039), but the total RBV dose was no different between them (49 ± 17% and 54 ± 18% of the target, P = 0.531). Sustained virological response (SVR) was achieved in 70% and 64% of them, respectively (P = 0.724). Conclusion:ITPA polymorphism influences hemoglobin levels during triple therapy, particularly during the first 12 weeks while telaprevir is given. With careful monitoring of anemia and prompt adjustment of RBV dose, SVR can be achieved comparably frequently between patients with CC and CA/AA genotypes. (Hepatology 2011)

Source

Also See: Evaluating patients for genetic variations impacts adherence to antiviral therapy