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

• DOI: 10.1002/hep.27009
• Publication Date: 2014-01-13T22:34:05Z
• Authors: Karolina Rembeck; Jesper Waldenström; Kristoffer Hellst...; Staffan Nilsson; Kristina Nyström; Anna Martner; Magnus Lindh; Gunnar Norkrans; Johan Westin; Court Pedersen; Martti Färkkilä; Nina Langeland; Mads Rauning Buhl; Kristine Mφrch; Peer Brehm Christ...; Martin Lagging
• Keywords: Pyrophosphatases; Tenofovir

The present study evaluated the impact of variations in inosine triphosphate pyrophosphatase (ITPase) gene (ITPA) on treatment outcome patients with hepatitis C virus (HCV) genotype 2/3 infection receiving peginterferon-α2a and lower, conventional 800 mg daily dose ribavirin. Previous studies using higher, weight-based ribavirin dosing report that carrying polymorphisms encoding reduced predicted ITPase activity show decreased risk ribavirin-induced anemia but increased thrombocytopenia, no elimination virus. In all, 354 treatment-naïve HCV 2/3-infected patients, enrolled a phase III trial (NORDynamIC), were genotyped for ITPA (rs1127354 rs7270101). Homo- or heterozygosity at Ars1127354 Crs7270101 , entailing activity, was observed 37% associated likelihood achieving sustained virological response (SVR) (P = 0.0003 univariate P 0.0002 multivariate analyses) accompanied by relapse among treatment-adherent patients. association between variants SVR remained significant when subdivided 12- 24-week duration arms, genotype, fibrosis stage, IL28B not secondary to improved adherence therapy less pronounced anemia. Gene predicting also < 0.0001), thrombocytopenia 0.007), lower concentrations 0.02). These findings demonstrate novel ribavirin-like efficacy chronic mediated risk. We hypothesize (63%) being homozygous both major alleles, leading normal may benefit more from addition future regimens spite concomitant