Variants of the inosine triphosphate pyrophosphatase gene are associated with reduced relapse risk following treatment for HCV genotype 2/3.
Journal article, 2014

The present study evaluated the impact of variations in the inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) on treatment outcome in patients with hepatitis C virus (HCV) genotype 2/3 infection receiving peginterferon-α2a and lower, conventional 800 mg daily dose of ribavirin. Previous studies using higher, weight-based ribavirin dosing report that patients carrying polymorphisms encoding reduced predicted ITPase activity show decreased risk of ribavirin-induced anemia but increased risk of thrombocytopenia, with no impact on elimination of virus. Three hundred fifty-four treatment naïve HCV genotype 2/3 infected patients, enrolled in a phase III trial (NORDynamIC), were genotyped for ITPA (rs1127354 and rs7270101). Homo- or heterozygosity at Ars1127354 or Crs7270101, entailing reduced ITPase activity, was observed in 37% of patients and was associated with increased likelihood of achieving sustained virological response (SVR) (P=0.0003 in univariate and multivariate analyses) accompanied by a reduced risk of relapse among treatment-adherent patients. The association between ITPA variants and SVR remained significant when patients were subdivided by the 12- and 24-week treatment duration arms, HCV genotype, fibrosis stage and IL28B genotype, and was not secondary to improved adherence to therapy or less pronounced anemia. Gene variants predicting reduced predicted ITPase activity also were associated with decreased risk of anemia (P<0.0001), increased risk of thrombocytopenia (P=0.007), and lower ribavirin concentrations (P=0.02). Conclusion: These findings demonstrate a novel ribavirin-like association between polymorphisms at ITPA and treatment efficacy in chronic hepatitis C mediated by reduced relapse risk. We hypothesize that patients (63%) being homozygous for both major alleles, leading to normal ITPase activity, may benefit more from the addition of ribavirin to present and future treatment regimens for HCV in spite of concomitant increased risk of anemia.


Karolina Rembeck

University of Gothenburg

Jesper Waldenström

University of Gothenburg

Kristoffer Hellstrand

University of Gothenburg

Staffan Nilsson

Chalmers, Mathematical Sciences, Mathematical Statistics

University of Gothenburg

Kristina Nyström

University of Gothenburg

Anna Martner

University of Gothenburg

Magnus Lindh

University of Gothenburg

Gunnar Norkrans

University of Gothenburg

Johan Westin

University of Gothenburg

Court Pedersen

University of Southern Denmark

Martti Färkkilä

University of Helsinki

Nina Langeland

Helse Bergen Haukeland University Hospital

Mads Rauning Buhl

Aarhus University

Kristine Mørch

Helse Bergen Haukeland University Hospital

Peer B Christensen

University of Southern Denmark

Martin Lagging

University of Gothenburg


0270-9139 (ISSN) 1527-3350 (eISSN)

Vol. 59 6 2131-2139

Subject Categories

Infectious Medicine





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9/6/2018 1