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

Published

Journal Article

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; R(2) = 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 R(2) = 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.

Full Text

Duke Authors

Cited Authors

  • Clark, PJ; Aghemo, A; Degasperi, E; Galmozzi, E; Urban, TJ; Vock, DM; Patel, K; Thompson, AJ; Rumi, MG; D'Ambrosio, R; Muir, AJ; Colombo, M

Published Date

  • December 2013

Published In

Volume / Issue

  • 20 / 12

Start / End Page

  • 858 - 866

PubMed ID

  • 24304455

Pubmed Central ID

  • 24304455

Electronic International Standard Serial Number (EISSN)

  • 1365-2893

Digital Object Identifier (DOI)

  • 10.1111/jvh.12113

Language

  • eng

Conference Location

  • England