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Protease inhibitors‐based therapy induces acquired spherocytic‐like anaemia and ineffective erythropoiesis in chronic hepatitis C virus patients

Protease inhibitors‐based therapy induces acquired spherocytic‐like anaemia and ineffective... Background & Aims The addition of protease inhibitors, boceprevir (BOC) or telaprevir (TRV), to peg‐interferon and ribavirin (PR) increases the incidence of anaemia in patients with chronic hepatitis C virus (HCV) infection. Although genetic variants in inosine triphosphatase (ITPA) gene have been linked to the haemolytic anaemia induced by PR, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic HCV patients with combined therapy. Methods We studied 59 patients with chronic HCV genotype‐1: 29 treated with TRV/PR and 30 with BOC/PR. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. IL28B and ITPA polymorphisms were also evaluated. Results We found early acute normochromic normocytic haemolytic anaemia (4–8 weeks) followed by a late macrocytic hypo‐regenerative anaemia with inappropriate low reticulocyte count (12–24 weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane‐cytoskeleton stability; (v) increased release of erythroid microparticles. ITPA polymorphisms impacted only the early phase of anaemia. Conclusions The bimodal pattern of anaemia in chronic HCV patients on triple therapy might be because of acquired spherocytic‐like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Liver International Wiley

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Publisher
Wiley
Copyright
© 2016 John Wiley & Sons A/S
ISSN
1478-3223
eISSN
1478-3231
DOI
10.1111/liv.12900
pmid
26104535
Publisher site
See Article on Publisher Site

Abstract

Background & Aims The addition of protease inhibitors, boceprevir (BOC) or telaprevir (TRV), to peg‐interferon and ribavirin (PR) increases the incidence of anaemia in patients with chronic hepatitis C virus (HCV) infection. Although genetic variants in inosine triphosphatase (ITPA) gene have been linked to the haemolytic anaemia induced by PR, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic HCV patients with combined therapy. Methods We studied 59 patients with chronic HCV genotype‐1: 29 treated with TRV/PR and 30 with BOC/PR. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. IL28B and ITPA polymorphisms were also evaluated. Results We found early acute normochromic normocytic haemolytic anaemia (4–8 weeks) followed by a late macrocytic hypo‐regenerative anaemia with inappropriate low reticulocyte count (12–24 weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane‐cytoskeleton stability; (v) increased release of erythroid microparticles. ITPA polymorphisms impacted only the early phase of anaemia. Conclusions The bimodal pattern of anaemia in chronic HCV patients on triple therapy might be because of acquired spherocytic‐like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis.

Journal

Liver InternationalWiley

Published: Jan 1, 2016

Keywords: ; ; ;

References