Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose reduction; however, their impact in real-life clinic patient cohorts remains to be defined. We studied 193 clinic patients with chronic hepatitis C infection of mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354 and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable models tested the association with anaemia at 4 weeks of treatment [including decline in haemoglobin (g/dL); haemoglobin <10 g/dL and haemoglobin decline >3 g/dL]; ribavirin dose reduction and EPO use and explored sustained viral response (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with less reduction in haemoglobin level (P < 0.001; R2 = 0.34), less ribavirin dose reduction (OR 0.42; (95% CI = 0.23-0.77); P = 0.005) and less EPO use [OR 0.53; (0.30-0.94); P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70; (1.02-2.83); P = 0.041] independently of clinical covariates (adjusted R2 = 0.31). In this clinical cohort, ITPA deficiency helped predict the risk of on-treatment anaemia, ribavirin dose reduction, need for EPO support and was associated with SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for ITPA deficiency may have clinical utility.

Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy / P.J. Clark, A. Aghemo, E. Degasperi, E. Galmozzi, T.J. Urban, D.M. Vock, K. Patel, A.J. Thompson, M.G. Rumi, R. D'Ambrosio, A.J. Muir, M. Colombo. - In: JOURNAL OF VIRAL HEPATITIS. - ISSN 1352-0504. - 20:12(2013), pp. 858-866.

Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy

A. Aghemo;E. Degasperi;E. Galmozzi;M.G. Rumi;R. D'Ambrosio;M. Colombo
2013

Abstract

Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose reduction; however, their impact in real-life clinic patient cohorts remains to be defined. We studied 193 clinic patients with chronic hepatitis C infection of mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354 and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable models tested the association with anaemia at 4 weeks of treatment [including decline in haemoglobin (g/dL); haemoglobin <10 g/dL and haemoglobin decline >3 g/dL]; ribavirin dose reduction and EPO use and explored sustained viral response (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with less reduction in haemoglobin level (P < 0.001; R2 = 0.34), less ribavirin dose reduction (OR 0.42; (95% CI = 0.23-0.77); P = 0.005) and less EPO use [OR 0.53; (0.30-0.94); P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70; (1.02-2.83); P = 0.041] independently of clinical covariates (adjusted R2 = 0.31). In this clinical cohort, ITPA deficiency helped predict the risk of on-treatment anaemia, ribavirin dose reduction, need for EPO support and was associated with SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for ITPA deficiency may have clinical utility.
erythropoietin; inosine triphosphatase; ribavirin-induced haemolysis; single nucleotide polymorphism; Aged; Anemia; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Interferons; Male; Metabolism, Inborn Errors; Middle Aged; Pyrophosphatases; Ribavirin; Treatment Outcome; Hepatology; Infectious Diseases; Virology
Settore MED/12 - Gastroenterologia
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/259750
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