{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T03:31:47Z","timestamp":1784950307980,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T00:00:00Z","timestamp":1436832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"PRIN","award":["AI: 201228PNX83"],"award-info":[{"award-number":["AI: 201228PNX83"]}]},{"name":"FUR_UNIVR"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>The addition of protease inhibitors, boceprevir (<jats:styled-content style=\"fixed-case\">BOC<\/jats:styled-content>) or telaprevir (<jats:styled-content style=\"fixed-case\">TRV<\/jats:styled-content>), to peg\u2010interferon and ribavirin (<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>) increases the incidence of anaemia in patients with chronic hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) infection. Although genetic variants in inosine triphosphatase (<jats:styled-content style=\"fixed-case\">ITPA<\/jats:styled-content>) gene have been linked to the haemolytic anaemia induced by <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> patients with combined therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied 59 patients with chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotype\u20101: 29 treated with <jats:styled-content style=\"fixed-case\">TRV<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> and 30 with <jats:styled-content style=\"fixed-case\">BOC<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content>. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24\u00a0weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>28B and <jats:styled-content style=\"fixed-case\">ITPA<\/jats:styled-content> polymorphisms were also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found early acute normochromic normocytic haemolytic anaemia (4\u20138\u00a0weeks) followed by a late macrocytic hypo\u2010regenerative anaemia with inappropriate low reticulocyte count (12\u201324\u00a0weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane\u2010cytoskeleton stability; (v) increased release of erythroid microparticles. <jats:styled-content style=\"fixed-case\">ITPA<\/jats:styled-content> polymorphisms impacted only the early phase of anaemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The bimodal pattern of anaemia in chronic <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> patients on triple therapy might be because of acquired spherocytic\u2010like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of <jats:styled-content style=\"fixed-case\">PR<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TRV<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">BOC<\/jats:styled-content> on erythropoiesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12900","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T04:56:51Z","timestamp":1435035411000},"page":"49-58","source":"Crossref","is-referenced-by-count":11,"title":["Protease inhibitors\u2010based therapy induces acquired spherocytic\u2010like anaemia and ineffective erythropoiesis in chronic hepatitis C virus patients"],"prefix":"10.1111","volume":"36","author":[{"given":"Francesca","family":"Lupo","sequence":"first","affiliation":[{"name":"Department of Medicine University of Verona and AOUI\u2010Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Russo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli 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