J Korean Med Sci.  2013 Aug;28(8):1213-1219. 10.3346/jkms.2013.28.8.1213.

The Impact of Inosine Triphosphatase Variants on Hemoglobin Level and Sustained Virologic Response of Chronic Hepatitis C in Korean

• Kim JS
• Ahn SM
• Jung YK
• Kwon OS
• Kim YS
• Choi DJ
• Kim JH

• KMID: 1793028
• DOI: http://doi.org/10.3346/jkms.2013.28.8.1213

Abstract

Two variants of the inosine triphosphatase (ITPA: rs1127354, rs7270101) gene cause ITPA deficiency and protect against the hemolytic toxicity of ribavirin. We investigated the clinical significance of ITPA variants in Korean patients treated with pegylated interferon (PEG-IFN) plus ribavirin. Of the 133 patients, 108 were CC and 25 were non-CC at rs1127354 (groups A and B, respectively). On the other hand, at rs7270101 all 133 were AA. The mean values of Hemoglobin (Hgb) after 4, 8, and 12 weeks of treatment in groups A and B were 12.2 and 14.0, 11.8 and 13.2, and 11.5 and 12.9, respectively (P=0.001, 0.036, 0.036). Sustained virologic response (SVR) was achieved in 67.8% (40/59) of genotype 1 patients and in 75% (27/36) of non-genotype 1 patients. Regarding ITPA variants, SVR was achieved by 66% and 80% of genotype 1 (P=0.282), and by 78% and 71% (P=0.726) of non-genotype 1. SVR was not significantly different in groups A and B. In conclusion, non-CC at rs1127354 without involvement of rs7270101 is strongly associated with protection from ribavirin-induced anemia, however, ITPA genotype is not associated with SVR.

Keyword

Hepatitis C, Chronic; Ribavirin; Anemia; ITPA; IL28B

MeSH Terms

Adult
Alleles
Antiviral Agents/therapeutic use
Asian Continental Ancestry Group/*genetics
Cohort Studies
Drug Therapy, Combination
Female
Genotype
Hemoglobins/*analysis
Hemolysis
Hepacivirus/genetics
Hepatitis C, Chronic/drug therapy/*genetics
Humans
Interferon-alpha/therapeutic use
Interleukins/genetics
Male
Middle Aged
Polyethylene Glycols/therapeutic use
Pyrophosphatases/*genetics
Recombinant Proteins/therapeutic use
Republic of Korea
Retrospective Studies
Ribavirin/therapeutic use
Treatment Outcome
Antiviral Agents
Hemoglobins
Interferon-alpha
Interleukins
Polyethylene Glycols
Pyrophosphatases
Recombinant Proteins
Ribavirin

Figure

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  Fig. 1 Frequencies of inosine triphosphatase polymorphism.

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  Fig. 2 Time dependent hemoglobin declines by ITPA genotype.

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  Fig. 3 Cumulative percentages of patients requiring ribavirin dose reduction after 4, 8, and 12 weeks of treatment by ITPA genotype.

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  Fig. 4 Virologic response by inosine triphosphatase genotype. RVR, Rapid virologic response; EVR, Early virologic response; SVR, Sustained virologic response.

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