{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:24:43Z","timestamp":1782483883674,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016545","name":"Roche Diagnostics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016545","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite achieving undetectable hepatitis B virus (HBV) DNA levels with nucleos(t)ide analogue (NA) therapy, patients with chronic hepatitis B (CHB) remain at risk of hepatocellular carcinoma (HCC). Novel covalently closed circular DNA activity biomarkers may improve risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To comprehensively assess the association between serum HBV RNA and hepatitis B core\u2010related antigen (HBcrAg) levels, measured upon achieving undetectable HBV DNA levels, and subsequent HCC development in NA\u2010treated patients with CHB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analysed 311 patients with CHB who achieved undetectable HBV DNA levels during NA therapy between 2000 and 2024. Serum HBV RNA (\u2265\u200910 copies\/mL) and HBcrAg (\u2265\u20092.1 log U\/mL) were measured in stored samples collected when HBV DNA first became undetectable. Cox regression analysis was performed to identify the factors associated with HCC development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During a median follow\u2010up of 11.0\u2009years, 31 (10.0%) patients developed HCC. At viral suppression, 132 (42.4%) patients had HBV RNA \u2265\u200910 copies\/mL. HCC incidence was significantly higher in patients with quantifiable HBV RNA than in those with unquantifiable HBV RNA (15\u2010year incidence, 17.8% vs. 8.8%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026). Quantifiable HBV RNA independently predicted HCC (adjusted hazard ratio [aHR], 3.313; 95% confidence interval [CI]: 1.154\u20139.507;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026). HBcrAg showed no association (aHR, 0.821; 95% CI: 0.253\u20132.669;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.743). Patients with quantifiable HBV RNA and albumin\u2010bilirubin score\u2009\u2265 \u22122.60 had the highest risk (5\u2010year incidence: 15.8%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HBV RNA levels at viral suppression predict HCC development in NA\u2010treated patients with CHB, outperforming HBcrAg. Incorporating HBV RNA assessment can improve risk\u2010stratified HCC surveillance strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70483","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T11:10:56Z","timestamp":1764673856000},"page":"1089-1098","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Hepatitis B Virus RNA Predicts Hepatocellular Carcinoma Despite Viral Suppression"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2211-495X","authenticated-orcid":false,"given":"Takashi","family":"Kumada","sequence":"first","affiliation":[{"name":"Department of Nursing, Faculty of Nursing Gifu Kyoritsu University  Gifu Japan"},{"name":"Department of Epidemiology, Infectious Disease Control, and Prevention Hiroshima University Institute of Biomedical and Health Sciences  Hiroshima 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