2014
DOI: 10.1002/hep.27009
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Variants of the inosine triphosphate pyrophosphatase gene are associated with reduced relapse risk following treatment for HCV genotype 2/3

Abstract: 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-a2a 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 thrombocyt… Show more

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Cited by 38 publications
(52 citation statements)
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“…ITPA polymorphism is related to the haemoglobin decline observed during HCV therapy [15]. The association between inosine triphosphatase (ITPA) genotypes and sustained virological response (SVR) rates in PEG-IFN + ribavirin therapy is controversial [17]. No data are available concerning the influence of IL28B and ITPA polymorphisms on response to HCV therapy and RBV-induced anaemia in the Tunisian population.…”
Section: Introductionmentioning
confidence: 99%
“…ITPA polymorphism is related to the haemoglobin decline observed during HCV therapy [15]. The association between inosine triphosphatase (ITPA) genotypes and sustained virological response (SVR) rates in PEG-IFN + ribavirin therapy is controversial [17]. No data are available concerning the influence of IL28B and ITPA polymorphisms on response to HCV therapy and RBV-induced anaemia in the Tunisian population.…”
Section: Introductionmentioning
confidence: 99%
“…In 2010, a genome-wide association study revealed that two functional variants in the inosine triphosphatase ( ITPA ) gene causing ITPA deficiency protect against RBV-induced hemolytic anemia and the need for RBV dose reduction in patients with HCV genotype 1 infection [14]. Recently, various studies could confirm these findings in CHC genotype 1 to 4 infected patients [1518]. ITPA variants could predict Hb decline during therapy in patients treated with PEG-IFN-α/RBV as well as in patients treated Telaprevir and PEG-IFN-α/RBV [19].…”
Section: Introductionmentioning
confidence: 99%
“…The mechanism by which reduced ITPase activity prevents ribavirininduced anemia has been hypothesized to be secondary to less ATP depletion as ITP may substitute for GTP in the generation of AMP by adenylosuccinate synthetase, which in turn prevents erythrocyte membrane oxidative damage that mediates premature erythrocyte removal [63,64]. Aside from avoidance of ATP depletion, reduced ITPase activity additionally has been reported to be associated with reduced ribavirin plasma concentration after 4 weeks of therapy, which also may contribute to protection against anemia [65].…”
Section: Inosine Triphosphate Pyrophosphatase (Itpa) Genetic Variantsmentioning
confidence: 99%
“…The study by Kurosaki et al noted an association between increased likelihood of achieving SVR and ITPA A variant of rs1127354 carriage among a subset of Japanese HCV genotype 1 infected patients with the favorable IL28B rs8099917 TT variant, but improved ribavirin adherence could not be ruled out as a possible confounder [67]. In the NORDynamIC study enrolling HCV genotype 2 or 3 infected patients receiving lower, conventional 800 mg daily dose of ribavirin in combination with pegIFN-α, a ribavirin-like association between polymorphisms entailing reduced ITPase activity and treatment efficacy mediated by reduced relapse risk was reported among adherent patients [65].…”
Section: Inosine Triphosphate Pyrophosphatase (Itpa) Genetic Variantsmentioning
confidence: 99%
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