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ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection.

Maan R, van der Meer AJ, Brouwer WP, Plompen EP, Sonneveld MJ, Roomer R, van der Eijk AA, Groothuismink ZM, Hansen BE, Veldt BJ, Janssen HL, Boonstra A, de Knegt RJ - PLoS ONE (2015)

Bottom Line: By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment.Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024).Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.

ABSTRACT

Background/objective: Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV.

Patients and methods: This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed.

Results: In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024).

Conclusion: Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently.

No MeSH data available.


Related in: MedlinePlus

ITPase deficiency, dose reductions, EPO and blood transfusions.Percentage of patients with at least one dose reduction of RBV or PegIFN, at least one blood transfusion or one dose of EPO during treatment. White bars represent the patients with normal ITPase activity and the black bars represent patients with ITPase deficiency. Abbreviations: ITPase, inosine triphosphate pyrophosphatase; RBV, ribavirin; PegIFN, pegylated interferon; EPO, erythropoietin.
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pone.0139317.g002: ITPase deficiency, dose reductions, EPO and blood transfusions.Percentage of patients with at least one dose reduction of RBV or PegIFN, at least one blood transfusion or one dose of EPO during treatment. White bars represent the patients with normal ITPase activity and the black bars represent patients with ITPase deficiency. Abbreviations: ITPase, inosine triphosphate pyrophosphatase; RBV, ribavirin; PegIFN, pegylated interferon; EPO, erythropoietin.

Mentions: In total, 20 (9%) patients underwent at least one dose reduction of RBV and 44 (21%) patients at least one dose reduction of PegIFN. At least one blood transfusion was given to 27 (13%) patients and 12 (6%) patients received at least one dose of EPO. Nineteen (13%) patients with normal ITPase activity underwent at least one dose reduction of RBV, whereas one (2%) patient with ITPase deficiency underwent at least one dose reduction (p = 0.014, Fig 2). The dose of PegIFN was reduced among 36 (24%) patients with normal ITPase activity and among eight (13%) patients with ITPase deficiency (p = 0.085). Blood transfusion and EPO were administered to 23 (15%) and twelve (8%) patients with normal ITPase; and to 4 (7%) and none (0%) of the patients with ITPase deficiency (p = 0.089 and p = 0.024, respectively).


ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection.

Maan R, van der Meer AJ, Brouwer WP, Plompen EP, Sonneveld MJ, Roomer R, van der Eijk AA, Groothuismink ZM, Hansen BE, Veldt BJ, Janssen HL, Boonstra A, de Knegt RJ - PLoS ONE (2015)

ITPase deficiency, dose reductions, EPO and blood transfusions.Percentage of patients with at least one dose reduction of RBV or PegIFN, at least one blood transfusion or one dose of EPO during treatment. White bars represent the patients with normal ITPase activity and the black bars represent patients with ITPase deficiency. Abbreviations: ITPase, inosine triphosphate pyrophosphatase; RBV, ribavirin; PegIFN, pegylated interferon; EPO, erythropoietin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595504&req=5

pone.0139317.g002: ITPase deficiency, dose reductions, EPO and blood transfusions.Percentage of patients with at least one dose reduction of RBV or PegIFN, at least one blood transfusion or one dose of EPO during treatment. White bars represent the patients with normal ITPase activity and the black bars represent patients with ITPase deficiency. Abbreviations: ITPase, inosine triphosphate pyrophosphatase; RBV, ribavirin; PegIFN, pegylated interferon; EPO, erythropoietin.
Mentions: In total, 20 (9%) patients underwent at least one dose reduction of RBV and 44 (21%) patients at least one dose reduction of PegIFN. At least one blood transfusion was given to 27 (13%) patients and 12 (6%) patients received at least one dose of EPO. Nineteen (13%) patients with normal ITPase activity underwent at least one dose reduction of RBV, whereas one (2%) patient with ITPase deficiency underwent at least one dose reduction (p = 0.014, Fig 2). The dose of PegIFN was reduced among 36 (24%) patients with normal ITPase activity and among eight (13%) patients with ITPase deficiency (p = 0.085). Blood transfusion and EPO were administered to 23 (15%) and twelve (8%) patients with normal ITPase; and to 4 (7%) and none (0%) of the patients with ITPase deficiency (p = 0.089 and p = 0.024, respectively).

Bottom Line: By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment.Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024).Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.

ABSTRACT

Background/objective: Genetic polymorphisms in the inosine triphosphatase (ITPA) gene have been associated with the protection from early ribavirin(RBV)-induced hemolytic anemia among patients with chronic hepatitis C virus (HCV) infection. The aim of the present study was to investigate the association between the functional ITPA variants and hematological side effects during antiviral therapy with pegylated interferon (PegIFN) and RBV.

Patients and methods: This cohort study included all consecutive Caucasian patients treated for chronic HCV infection with PegIFN and RBV between 2000 and 2009 for whom a serum sample was available for genetic testing. The predicted inosine triphosphate pyrophosphatase (ITPase) activity was based on the genotypes of the SNPs rs1127354 and rs7270101. Decline in hemoglobin (Hb) during antiviral therapy, as well as dose reductions, blood transfusions and use of erythropoietin were assessed.

Results: In total, 213 patients were included. The predicted ITPase activity was normal among 152 (71%) patients; 61 (29%) patients had ITPase deficiency. By multivariable linear regression, RBV dose in mg per kilogram (Beta 0.09, 95%CI 0.04-0.13, p<0.001) and normal ITPase activity (Beta 0.89, 95%CI 0.64-1.14, p<0.001) were associated with more Hb decline at week 4 of treatment. Patients with normal ITPase activity underwent more dose adjustments of RBV than patients with ITPase deficiency (19(13%) vs 1(2%),p = 0.014) and received erythropoietin more frequently (12 (8%) vs 0 (0%),p = 0.024).

Conclusion: Genetic variants in the ITPA gene protected against RBV treatment-induced anemia among Caucasian patients with chronic HCV infection. Patients with normal ITPase activity underwent more dose reductions of RBV and received erythropoietin more frequently.

No MeSH data available.


Related in: MedlinePlus