Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C (original) (raw)
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Hepatology, 2011
Two functional variants in the inosine triphosphatase (ITPA) gene causing inosine triphosphatase (ITPase) deficiency protect against ribavirin (RBV)-induced hemolytic anemia and the need for RBV dose reduction in patients with genotype 1 hepatitis C virus (HCV). No data are available for genotype 2/3 HCV. We evaluated the association between the casual ITPA variants and on-treatment anemia in a well-characterized cohort of genotype 2/3 patients treated with variable-duration pegylated interferon alfa-2b (PEG-IFN-a2b) and RBV. Two hundred thirty-eight Caucasian patients were included in this retrospective study [185 (78%) with genotype 2 and 53 (22%) with genotype 3]. Patients were treated with PEG-IFN-a2b plus weight-based RBV (1000/1200 mg) for 12 (n 5 109) or 24 weeks (n 5 129). The ITPA polymorphisms rs1127354 and rs7270101 were genotyped, and an ITPase deficiency variable was defined that combined both ITPA variants according to their effect on ITPase activity. The primary endpoint was hemoglobin (Hb) reduction in week 4. We also considered Hb reduction over the course of therapy, the need for RBV dose modification, and the rate of sustained virological response (SVR). The ITPA variants were strongly and independently associated with protection from week 4 anemia (P 5 10 26 for rs1127354 and P 5 10 27 for rs7270101). Combining the variants into the ITPase deficiency variable increased the strength of association (P 5 10 211 ). ITPase deficiency protected against anemia throughout treatment. ITPase deficiency was associated with a delayed time to an Hb level < 10 g/dL (hazard ratio 5 0.25, 95% confidence interval 5 0.08-0.84, P 5 0.025) but not with the rate of RBV dose modification (required per protocol at Hb < 9.5 g/dL). There was no association between the ITPA variants and SVR. Conclusion: Two ITPA variants were strongly associated with protection against treatment-related anemia in patients with genotype 2/3 HCV, but they did not decrease the need for RBV dose reduction or increase the rate of SVR.
Antimicrobial agents and chemotherapy, 2012
Polymorphisms of the ITPA gene have been associated with anemia during combination therapy in hepatitis C virus (HCV)monoinfected patients. Our aim was to confirm this association in HIV/HCV-coinfected patients. In this prospective, observational study, 73 HIV/HCV-coinfected patients treated with pegylated interferon plus ribavirin (RBV) were enrolled. Two single nucleotide polymorphisms within or adjacent to the ITPA gene (rs1127354 and rs7270101) were genotyped. The associations between the ITPA genotype and anemia or treatment outcome were examined. Fifty-nine patients (80.8%) had CC at rs1127354, whereas 14 (19.2%) had a CA/AA ITPA genotype. Percent decreases from baseline hemoglobin level were significantly greater in patients with the CC genotype than in those with the CA/AA genotype at week 4 (P ؍ 0.0003), week 12 (P < 0.0001), and week 36 (P ؍ 0.0102) but not at the end of treatment. RBV dose reduction was more often needed in patients with the CC genotype than in those with the CA/AA genotype (odds ratio [OR] ؍ 11.81; 95% confidence interval [CI] ؍ 1.45 to 256.17; P ؍ 0.0039), as was erythropoietin therapy (OR ؍ 8.28; 95% CI ؍ 1.04 to 371.12; P ؍ 0.0057). Risk factors independently associated with percent hemoglobin nadir decrease were RBV dose reduction (OR ؍ 11.72; 95% CI ؍ 6.82 to 16.63; P < 0.001), baseline hemoglobin (OR ؍ 1.69; 95% CI ؍ 0.23 to 3.15; P ؍ 0.024), and body mass index (OR ؍ ؊0.7; 95% CI ؍ ؊1.43 to 0.03; P ؍ 0.061). ITPA polymorphism was not an independent predictor of sustained virological response. Polymorphisms at rs1127354 in the ITPA gene influence hemoglobin levels during combination HCV therapy and the need for RBV dose reduction and erythropoietin use in HIV/HCV-coinfected patients.
Antiviral Research, 2013
(AAM) is copyrighted and published by Elsevier. It is posted here by agreement between Elsevier and the University of Turin. Changes resulting from the publishing process-such as editing, corrections, structural formatting, and other quality control mechanisms-may not be reflected in this version of the text. The definitive version of the text was subsequently published in ANTIVIRAL RESEARCH, 100 (1), 2013, 10.1016/j.antiviral.2013.07.021. You may download, copy and otherwise use the AAM for non-commercial purposes provided that your license is limited by the following restrictions: (1) You may use this AAM for non-commercial purposes only under the terms of the CC-BY-NC-ND license. (2) The integrity of the work and identification of the author, copyright owner, and publisher must be preserved in any copy.
Indian Journal of Gastroenterology, 2016
Background Ribavirin (RBV)-induced anemia is one of the major causes of dose reduction and discontinuation of therapy for chronic hepatitis C (CHC) patients. We investigated the role of inosine triphosphate pyrophosphatase (ITPA) single nucleotide polymorphism (SNP) (rs1127354) in predicting RBV-induced anemia and thrombocytopenia among Egyptian patients with CHC genotype 4 infection. Methods One hundred and twenty Egyptian patients with CHC genotype 4 who had received standard of care combination therapy were enrolled in this study. Single nucleotide polymorphism at ITPA (rs1127354) was genotyped by realtime detection polymerase chain reaction. Results Hb levels between CC and non-CC groups were significantly different at weeks 4, 8, and 12. Hemoglobin decline was significantly higher among CC patient than non-CC patients at week 4 and week 8 of treatment. The RBV dose reduction was higher in CC than non-CC group. Platelet decline was significantly lower in CC patients than non-CC patients at baseline, 4, 12 weeks only. Conclusion Rs1127354 ITPA polymorphism was associated with RBV-induced anemia and thrombocytopenia in Egyptian patients with hepatitis C virus genotype 4 infection.
Antiviral therapy, 2017
Background: Single nucleotide polymorphisms (SNPs) at the ITPA gene are associated with haemolytic anaemia in chronic hepatitis C patients treated with pegylated interferon-ribavirin (RBV). Information in patients treated with interferon-free, direct-acting antivirals (DAA) is scarce. Methods: Median haemoglobin (Hb) levels were compared at baseline and at week 4, when ribavirin concentration achieves steady state, in all consecutive chronic hepatitis C patients treated with oral DAA plus RBV at our clinic. Results: Median Hb drop in 55 patients was greater in rs1127354-CC than-CA/AA (1.8 versus 0.7 g/dl; P=0.029), and in rs6051702-AA than-AC/CC carriers (2.2 versus 1.1 g/dl; P=0.016). Eleven (20%) patients experienced severe anaemia, defined as Hb drop >3 g/dl or to <10 g/dl. All of them were rs6051702-AA. Conclusions: Baseline testing of rs6051702 may identify the subset of patients at greatest risk for RBV-induced anaemia using interferon-free hepatitis C therapies.
2012
42 Background 43 Polymorphisms of the ITPA gene have been associated with anemia during 44 combination therapy in HCV mono-infected patients. Our aim was to confirm this 45 association in HIV/HCV co-infected patients 46 Methods 47 In this prospective, observational study, 73 HIV/HCV co-infected patients treated with 48 Peg-IFN plus RBV were enrolled. Two SNPs within or adjacent to ITPA gene (rs1127354 49 and rs7270101) were genotyped. The associations between the ITPA genotype and 50 anemia or treatment outcome were examined. 51 Results 52 Fifty-nine patients (80.8%) had CC at rs 1127354 whereas 14 (19.2%) had a CA/AA 53 ITPA genotype. Percent decreases from baseline hemoglobin level were significantly 54 greater in patients with CC than in those with CA/AA genotype at week 4 (P = 0.0003), 55 week 12 (P < 0.0001), week 36 (P = 0.0102), but not at the end of treatment. RBV dose 56 reduction was more often needed in patients with CC than in those with CA/AA 57 genotype (OR = 11.81;...
PloS one, 2015
Whether inosine triphosphatase (ITPA) gene polymorphisms predict anemia during interferon-free therapy in chronic hepatitis C virus (HCV)-infected patients is unknown. We examined the relationship between two ITPA polymorphisms, anemia, and sustained virological response 12 weeks post-treatment (SVR12) in patients receiving the NS3/4A protease inhibitor faldaprevir, the non-nucleoside polymerase inhibitor deleobuvir, and ribavirin. HCV genotype 1-infected, treatment-naïve patients (N = 362) were randomized and treated in one of five treatment arms with faldaprevir and deleobuvir with or without ribavirin. Two ITPA polymorphisms (rs1127354 and rs6051702) were genotyped and defined as ITPA-deficient (rs1127354 AA or AC; rs6051702 CC or CA) or ITPA-non-deficient (rs1127354 CC; rs6051702 AA) according to their association with ITPA deficiency. Baseline and on-treatment variables associated with anemia and SVR12 were identified using logistic regression. In the pooled ribavirin-containin...
Journal of gastroenterology and hepatology, 2017
It is unclear whether polymorphism in the inosine triphosphatase (ITPA) gene correlates with the reduction in hemoglobin (Hb) concentrations during sofosbuvir (SOF) and ribavirin (RBV) therapy. We investigated the effects of the ITPA polymorphism in Japanese patients with chronic hepatitis C virus genotype 2 infection treated with SOF/RBV therapy. In 106 patients treated with SOF/RBV therapy, we assessed the effects of the ITPA polymorphism (rs1127354) on anemia, RBV dose reduction, and sustained virological response (SVR). Of the 106 patients, 80 had the CC genotype, whereas 26 had a non-CC genotype in ITPA. Patients with the CC genotype had significantly larger reductions in Hb concentrations than those with a non-CC genotype throughout the treatment course. RBV dose reduction was required in 18/106 (17.0%) patients, with a significantly higher frequency in patients with the CC genotype than in those with a non-CC genotype (p = 0.010). In multivariate analysis, age ≥ 65 years (p =...