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

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 4weeks of treatment [including decline in haemoglobin (g/dL); haemoglobin <10g/dL and haemoglobin decline >3g/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.