{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:09:16Z","timestamp":1761664156327,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:00:00Z","timestamp":1608076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients even under effective long\u2010term oral antiviral therapy, but its pathogenesis in the setting of long\u2010standing inhibition of viral replication has not been completely elucidated. We investigated whether species of circulating cell\u2010free DNA (cfDNA) may be involved in the process of hepatocarcinogenesis in treated CHB patients. Serum samples were obtained from HBeAg\u2010negative CHB patients with (HCC cases, <jats:italic>n<\/jats:italic>\u00a0=\u00a037) or without HCC development during the first 5\u00a0years of oral antiviral therapy (controls, <jats:italic>n<\/jats:italic>\u00a0=\u00a074). HCC cases and controls were matched 1:2 for age, sex and platelets. Determination of different circulating cfDNA species (before HCC diagnosis in HCC cases) including total cfDNA quantity, levels of Alu repeat DNA and RNase P coding DNA, copies of mitochondrial DNA and levels of 5\u2010methyl\u20102\u2032\u2010deoxycytidine as an indicator of DNA methylation was performed. HCC cases compared with controls had higher median levels of Alu247 (123 vs 69 genomic equivalent, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.042) and RNase P coding DNA (68 vs 15 genomic equivalent, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). In contrast, median cfDNA concentration, Alu115 levels, Alu247\/Alu115 ratio as an index of DNA integrity and mitochondrial DNA copies did not differ significantly between HCC cases and controls. Receiver operating characteristic curve analysis showed that levels RNase P coding DNA offered good prediction of subsequent HCC development (c\u2010statistic: 0.80, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). In conclusion, serum levels of RNase P coding DNA are increased years before HCC diagnosis and could be potentially helpful in the prediction of the HCC risk in treated HBeAg\u2010negative CHB patients.<\/jats:p>","DOI":"10.1111\/jvh.13446","type":"journal-article","created":{"date-parts":[[2020,12,2]],"date-time":"2020-12-02T01:25:08Z","timestamp":1606872308000},"page":"464-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Circulating cell\u2010free DNA species affect the risk of hepatocellular carcinoma in treated chronic hepatitis B patients"],"prefix":"10.1111","volume":"28","author":[{"given":"Alkistis","family":"Papatheodoridi","sequence":"first","affiliation":[{"name":"Department of Physiology Medical School of National and Kapodistrian University of Athens  Athens Greece"},{"name":"Department of Clinical Therapeutics \u2018Alexandra\u2019 General Hospital of Athens Medical School of National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonios","family":"Chatzigeorgiou","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical School of National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lampros","family":"Chrysavgis","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical School of National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiotis","family":"Lembessis","sequence":"additional","affiliation":[{"name":"Department of Physiology Medical School of National and Kapodistrian University of Athens  Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Loglio","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico Division of Gastroenterology and Hepatology CRC \u2018A. M. and A. Migliavacca\u2019 Center for Liver Disease  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Floriana","family":"Facchetti","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico Division of Gastroenterology and Hepatology CRC \u2018A. M. and A. 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