Role of ITPA gene polymorphism in ribavirin-induced anemia and thrombocytopenia in Egyptian patients with chronic hepatitis C (original) (raw)
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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.
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.
Memórias do Instituto Oswaldo Cruz, 2015
Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes , respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.
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.
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 =...
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...
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;...