{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:30:44Z","timestamp":1769524244468,"version":"3.49.0"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,16]],"date-time":"2019-07-16T00:00:00Z","timestamp":1563235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; aims<\/jats:title><jats:p>We investigated the HCV\u2010RNA amount, variability and prevalence of resistance\u2010associated substitutions (RASs), in plasma, hepatic tumoral and non\u2010tumoral tissue samples in patients undergoing liver\u2010transplant\/hepatic\u2010resection (LT\/HR), because of hepatocellular carcinoma and\/or cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Eighteen HCV\u2010infected patients undergoing LT\/HR, 94.0% na\u00efve to direct\u2010acting antivirals (DAAs), were analysed. HCV\u2010RNA was quantified in all compartments. NS3\/NS5A\/NS5B in plasma and\/or in tumoral\/non\u2010tumoral tissues were analysed using Sanger and Ultra\u2010deep pyrosequencing (UDPS, 9\/18 patients). RASs prevalence, genetic\u2010variability and phylogenetic analysis were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At the time of LT\/HR, HCV\u2010RNA was quantifiable in all compartments of DAA\u2010na\u00efve patients and was generally lower in tumoral than in non\u2010tumoral tissues (median [IQR]\u00a0=\u00a04.0 [1.2\u20104.3] vs 4.3[3.1\u20104.9] LogIU\/\u00b5g RNA; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.193). The one patient treated with sofosbuvir\u00a0+\u00a0ribavirin represented an exception with HCV\u2010RNA quantifiable exclusively in the liver, but with higher level in tumoral than in non\u2010tumoral tissues (51 vs 7\u00a0IU\/\u00b5g RNA). RASs compartmentalization was found by Sanger in 4\/18 infected\u2010patients, and by UDPS in other two patients. HCV\u2010compartmentalization resulted to be associated with HBcAb\u2010positivity (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.013). UDPS showed approximately higher genetic\u2010variability in NS3\/NS5A sequences in all compartments. Phylogenetic\u2010analysis showed defined and intermixed HCV\u2010clusters among\/within all compartments, and were strongly evident in the only non\u2010cirrhotic patient, with plasma and non\u2010tumoral sequences generally more closely related.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Hepatic compartments showed differences in HCV\u2010RNA amount, RASs and genetic variability, with a higher segregation within the tumoral compartment. HBV coinfection influenced the HCV compartmentalization. These results highlight HCV\u2010strain diversifications within the liver, which could explain some of the failures occurring even today in the era of DAAs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14168","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T04:31:53Z","timestamp":1559881913000},"page":"1986-1998","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["HCV resistance compartmentalization within tumoral and non\u2010tumoral liver in transplanted patients with hepatocellular carcinoma"],"prefix":"10.1111","volume":"39","author":[{"given":"Maria C","family":"Sorbo","sequence":"first","affiliation":[{"name":"Chair of Virology, Department of Experimental Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Carioti","sequence":"additional","affiliation":[{"name":"Chair of Virology, Department of Experimental Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria C","family":"Bellocchi","sequence":"additional","affiliation":[{"name":"Chair of Virology, Department of Experimental Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FrancescoPaolo","family":"Antonucci","sequence":"additional","affiliation":[{"name":"Chair of Virology, Department of Experimental Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Sforza","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Transplant Unit, Department of Surgery Policlinico Tor Vergata\/Tor Vergata University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Lenci","sequence":"additional","affiliation":[{"name":"Hepatology Unit, Department of Systems Medicine Policlinico Tor Vergata\/Tor Vergata University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Ciancio Manuelli","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Transplant Unit, Department of Surgery Policlinico Tor Vergata\/Tor Vergata University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniele","family":"Armenia","sequence":"additional","affiliation":[{"name":"Chair of Virology, Department of Experimental Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"De Leonardis","sequence":"additional","affiliation":[{"name":"Hepatology Unit, Department of Systems Medicine Policlinico Tor Vergata\/Tor Vergata University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Milana","sequence":"additional","affiliation":[{"name":"Hepatology Unit, Department of Systems Medicine Policlinico Tor Vergata\/Tor Vergata University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tommaso M","family":"Manzia","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Transplant Unit, Department of Surgery Policlinico Tor Vergata\/Tor Vergata University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Angelico","sequence":"additional","affiliation":[{"name":"Hepatology Unit, Department of Systems Medicine Policlinico Tor Vergata\/Tor Vergata University Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Tisone","sequence":"additional","affiliation":[{"name":"Hepatobiliary and Transplant Unit, Department of Surgery Policlinico Tor Vergata\/Tor Vergata University Rome 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