Association of ITPA gene variation and serum ribavirin concentration with a decline in blood cell concentrations during pegylated interferon-alpha plus ribavirin therapy for chronic hepatitis C
Hepatology International,  Clinical Article

Nakagawa M et al. – Despite the fact that inosine triphosphatase (ITPA) variants were less likely to develop anemia, patients with low baseline platelet (PLT) counts were difficult to treat, especially those with the ITPA–CA/AA genotype. These results may give a valuable pharmacogenetic diagnostic tool for the tailoring of dosing to minimize drug–induced adverse events.

Methods
  • A total of 300 hepatitis C patients treated with PEG-IFN plus ribavirin were analyzed.
  • Genetic polymorphisms were determined in ITPA and the quantitative reduction in blood cells from the baseline was analyzed every 4 weeks for the duration of treatment and after the end of therapy.
  • The decline in hemoglobin (Hb) or platelet (PLT) level at week 4 compared to baseline was also assessed according to ribavirin concentrations.

Results
  • Patients with the ITPA-CA/AA genotypes showed a lower degree of Hb reduction throughout therapy than those with the ITPA-CC genotype and a marked difference in mean Hb reduction was found at week 4 (CA/AA -1.0 vs. CC -2.8, p < 0.001).
  • The ITPA-CC genotype had significantly less reduction in the mean platelet count than the ITPA-CA/AA genotypes early during treatment (p < 0.001 for weeks 4 and 8).
  • Patients with the ITPA-CA/AA genotypes were less likely to develop anemia, regardless of the concentration of ribavirin.
  • Patients with baseline PLT counts below 130 × 103/μl had a significantly lower tendency to achieve sustained virological response (SVR), especially those with the ITPA-CA/AA genotypes.
  • ITPA gene variation was not extracted by multivariable analysis as an important predictor of SVR.

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