{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T15:38:45Z","timestamp":1789227525121,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24fk0310512"],"award-info":[{"award-number":["JP24fk0310512"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25fk0310534"],"award-info":[{"award-number":["JP25fk0310534"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Nucleos(t)ide analogs (NUCs) are used in the treatment of chronic hepatitis B (CHB). It is still uncertain whether the risk of incident hepatocellular carcinoma (HCC) continues beyond 5 or 10\u00a0years after the initiation of NUC treatment. We aimed to elucidate this in CHB patients receiving long\u2010term NUC treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a multicenter, observational study that included patients who began NUC treatment between July 2000 and March 2019; patients were retrospectively enrolled up to March 2019 and followed up until August 2024.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 737 CHB patients (156 with cirrhosis) who started NUC treatment, 147 developed HCC during a median follow\u2010up period of 144.2\u00a0months. The 5\u2010, 10\u2010, and 15\u2010year cumulative HCC rates were 11.2%, 18.4%, and 23.1%, respectively. Independent risk factors for subsequent HCC occurrence included older age, male sex, cirrhosis, low platelet count, low ALT levels, and high <jats:italic>\u03b3<\/jats:italic>\u2010GTP levels at NUC initiation. After 5\u00a0years, the risk factors were cirrhosis, high <jats:italic>\u03b3<\/jats:italic>\u2010GTP levels, and high AFP levels, whereas after 10\u00a0years, they were cirrhosis and diabetes. Landmark analysis revealed that the 5\u2010year cumulative HCC incidence was 8.1% at 5\u00a0years and 5.8% at 10\u00a0years after NUC initiation. In noncirrhotic patients, cumulative HCC incidence at 5\u00a0years was 5.8%, whereas 5\u2010year cumulative incidences starting at 5 and 10\u00a0years were 4.1% and 4.8%, respectively, remaining stable over time.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The risk of HCC persists long after NUC initiation. In noncirrhotic patients, the risk remains stable more than 10\u00a0years after NUC treatment initiation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.14225","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T08:27:45Z","timestamp":1750148865000},"page":"1228-1238","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Risk of Developing Hepatocellular Carcinoma Persists in Chronic Hepatitis B Patients Even After the Long\u2010Term Administration of Nucleos(t)ide Analogs"],"prefix":"10.1111","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8634-2922","authenticated-orcid":false,"given":"Kazuhiro","family":"Murai","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology The University of Osaka Graduate School of Medicine  Suita 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