title: Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy.
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; 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.
authors.affiliation: GI/Hepatology, Duke Clinical Research Institute, Durham, NC, USA; Princess Alexandra Hospital, Brisbane, Qld, Australia; Queensland Institute of Medical Research, Brisbane, Qld, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Clark
authors.forename: A
authors.initials: A
authors.lastname: Aghemo
authors.forename: E
authors.initials: E
authors.lastname: Degasperi
authors.forename: E
authors.initials: E
authors.lastname: Galmozzi
authors.forename: T J
authors.initials: TJ
authors.lastname: Urban
authors.forename: D M
authors.initials: DM
authors.lastname: Vock
authors.forename: K
authors.initials: K
authors.lastname: Patel
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: M G
authors.initials: MG
authors.lastname: Rumi
authors.forename: R
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: A J
authors.initials: AJ
authors.lastname: Muir
authors.forename: M
authors.initials: M
authors.lastname: Colombo
mesh_terms: D000368:Aged; D000740:Anemia / Q000139:chemically induced* / Q000453:epidemiology*; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis*; D008875:Middle Aged; D011755:Pyrophosphatases / Q000172:deficiency*; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D012254:Ribavirin; D007372:Interferons; D011755:Pyrophosphatases
keywords: erythropoietin; inosine triphosphatase; ribavirin-induced haemolysis; single nucleotide polymorphism