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


CONCLUSIONS
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.
Department of Hepatology, Toranomon Hospital, Tokyo, Japan. fumitakas@toranomon.gr.jp
Fumitaka
F
Suzuki
Yoshiyuki
Y
Suzuki
Norio
N
Akuta
Hitomi
H
Sezaki
Miharu
M
Hirakawa
Yusuke
Y
Kawamura
Tetsuya
T
Hosaka
Masahiro
M
Kobayashi
Satoshi
S
Saito
Yasuji
Y
Arase
Kenji
K
Ikeda
Mariko
M
Kobayashi
Kazuaki
K
Chayama
Naoyuki
N
Kamatani
Yusuke
Y
Nakamura
Yuzo
Y
Miyakawa
Hiromitsu
H
Kumada
D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000208:ethnology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009842:Oligopeptides / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000097630:Inosine Triphosphatase
D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; C486464:telaprevir; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C417083:peginterferon alfa-2b