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

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

Rembeck, Karolina (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Waldenström, Jesper, 1985 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Hellstrand, Kristoffer, 1956 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Nilsson, Staffan, 1956 (author): Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg

Nyström, Kristina, 1977 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Martner, Anna, 1979 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Lindh, Magnus, 1960 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Norkrans, Gunnar, 1944 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Westin, Johan, 1965 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

Pedersen, Court (author): Syddansk Universitet,University of Southern Denmark

Färkkilä, Martti (author): Helsingin Yliopisto,University of Helsinki

Langeland, Nina (author): Helse Bergen Haukeland University Hospital

Buhl, Mads Rauning (author): Århus Universitet,Aarhus University

Mörch, Kristine (author): Helse Bergen Haukeland University Hospital

Christensen, Peer Brehm (author): Syddansk Universitet,University of Southern Denmark

Lagging, Martin, 1965 (author): Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine,University of Gothenburg

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2014-04-25
2014
English.
In: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 59:6, s. 2131-2139

Related links:: https://aasldpubs.on...; show more...; http://dx.doi.org/10...; https://gup.ub.gu.se...; https://doi.org/10.1...; https://research.cha...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

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By the author/editor: Rembeck, Karolin ...; Waldenström, Jes ...; Hellstrand, Kris ...; Nilsson, Staffan ...; Nyström, Kristin ...; Martner, Anna, 1 ...; show more...; Lindh, Magnus, 1 ...; Norkrans, Gunnar ...; Westin, Johan, 1 ...; Pedersen, Court; Färkkilä, Martti; Langeland, Nina; Buhl, Mads Rauni ...; Mörch, Kristine; Christensen, Pee ...; Lagging, Martin, ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Infectious Medic ...

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By the university: University of Gothenburg; Chalmers University of Technology

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

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