Abstract

BackgroundSevere anemia is a common side effect of Pegylated Interferon + Ribavirin (PR) and Telaprevir (TVR) in hepatitis C virus (HCV) genotype 1 patients with advanced fibrosis or cirrhosis (F3–F4). Inosine triphosphatase (ITPA) genetic variants are associated with RBV- induced anemia and dose reduction.AimTo test the association of ITPA polymorphisms rs1127354 and rs7270101 with hemoglobin (Hb) decline, need for RBV dose reduction (RBV DR), erythropoietin (EPO) support and blood transfusions during the first 12 weeks of TVR triple therapy.Materials and Methods69 consecutive HCV-1 patients (mean age 57 years) with F3-F4 who received PR and TVR were genotyped for ITPA polymorphisms rs1127354 and rs7270101. Estimated ITPA deficiency was graded on severity (0–3, no deficiency/mild/moderate/severe).ResultsITPA deficiency was absent in 48 patients (70%), mild in 12 (17%) and moderate in 9 patients (13%). Mean week 4 Hb decline was higher in non ITPA deficient patients (3,85 g/dL) than in mildly or moderately ITPA deficient patients (3,07 g/dL and 1,67 g/dL, p<0.0001). Grade 3–4 anemia developed in 81% non ITPA deficient patients versus 67% mild deficient and 55% moderate deficient patients (p = ns). Grade of ITPA deficiency was not associated with RbvDR (no deficiency: 60%, mild: 58%, moderate: 67%; p = ns), EPO use (no deficiency: 65%, mild: 58%, moderate:56%; p = ns) or need for blood transfusion (no deficiency: 27%, mild: 17%, moderate: 33%; p = ns).ConclusionsIn patients with F3–F4 chronic hepatitis C receiving TVR based therapy, ITPA genotype does not impact on the management of early anemia.

Highlights

  • The first generation inhibitors of the Hepatitis C virus (HCV) NS3 protein, Telaprevir (TVR) and Boceprevir (BOC), when combined with Pegylated Interferon and Ribavirin (PR) are the standard of care regimen for patients with hepatitis C virus (HCV)-1 [1]

  • In patients with F3–F4 chronic hepatitis C receiving TVR based therapy, Inosine triphosphatase (ITPA) genotype does not impact on the management of early anemia

  • 9 (13%) patients were treatment naıve, the remaining 60 treatment experienced patients were classified as relapsers (38%), partial responders (14%), null responders (32%) or virological breakthroughs (3%) to a previous Pegylated Interferon + Ribavirin (PR) treatment. 48 patients (70%) had no ITPA deficiency, the remaining 21 (30%) showed varying degrees of deficiency: mild ITPA deficiency was found in 12 (17%) and moderate deficiency was found in 9 patients (13%)

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Summary

Introduction

The first generation inhibitors of the Hepatitis C virus (HCV) NS3 protein, Telaprevir (TVR) and Boceprevir (BOC), when combined with Pegylated Interferon and Ribavirin (PR) are the standard of care regimen for patients with HCV-1 [1]. This triple therapy regimen has provided an increase in achievable sustained virological response (SVR) rates compared to PR both in treatment naive patients, as well as in patients who have failed to respond to a previous course of PR. Inosine triphosphatase (ITPA) genetic variants are associated with RBV- induced anemia and dose reduction

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