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

Clark, P. J., Aghemo, A., Degasperi, E., Galmozzi, E., Urban, T. J., Vock, D. M., Patel, K., Thompson, A. J., Rumi, M. G., D'Ambrosio, R., Muir, A. J. and Colombo, M. (2013) Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy. Journal of Viral Hepatitis, 20 12: 858-866. doi:10.1111/jvh.12113


Author Clark, P. J.
Aghemo, A.
Degasperi, E.
Galmozzi, E.
Urban, T. J.
Vock, D. M.
Patel, K.
Thompson, A. J.
Rumi, M. G.
D'Ambrosio, R.
Muir, A. J.
Colombo, M.
Title Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy
Journal name Journal of Viral Hepatitis   Check publisher's open access policy
ISSN 1352-0504
1365-2893
Publication date 2013
Year available 2013
Sub-type Article (original research)
DOI 10.1111/jvh.12113
Open Access Status
Volume 20
Issue 12
Start page 858
End page 866
Total pages 9
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing Ltd.
Collection year 2014
Language eng
Subject 2721 Hepatology
2725 Infectious Diseases
2406 Virology
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.
Keyword Erythropoietin
Inosine Triphosphatase
Ribavirin-induced haemolysis
Single nucleotide polymorphism
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Thu, 17 Jul 2014, 09:18:43 EST by Anthony Yeates on behalf of Medicine - Princess Alexandra Hospital