{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T04:18:25Z","timestamp":1786249105673,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20fk0210067h0001"],"award-info":[{"award-number":["JP20fk0210067h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>The serum hepatitis B core\u2010related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aims to investigate the virological characteristics of HBcrAg in chronic hepatitis B (CHB) patients and to reveal the hepatocellular carcinoma (HCC) risk factors of hepatitis B e antigen (HBeAg)\u2010negative patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hepatitis B core\u2010related antigen was measured in 245 naive CHB patients before receiving nucleoside\/nucleotide analog (NA) therapy. All patients were receiving NA (entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide) continuously for more than 1\u00a0year until the end of follow\u2010up, and they did not have a history of HCC. Hepatitis B viral status was compared between 106 HBeAg\u2010positive and 139 HBeAg\u2010negative patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Median HBcrAg levels were significantly higher in HBeAg\u2010positive patients than in HBeAg\u2010negative patients (&gt;\u00a06.8 <jats:italic>vs<\/jats:italic> 3.7\u00a0log U\/mL, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). In HBeAg\u2010negative patients, higher HBcrAg levels were associated with cirrhosis (119 chronic hepatitis\/20 cirrhosis\u00a0=\u00a03.5\/4.7\u00a0log U\/mL, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03) and higher serum hepatitis B virus DNA. During a median follow\u2010up of 5.28 (1.03\u201312.0) years, the 5\u2010year cumulative HCC incidence rate was 5.4% in the HBeAg\u2010negative cohort. In the multivariate Cox regression analysis, higher HBcrAg levels at 1\u00a0year were independent predictive factors for HCC development in HBeAg\u2010negative patients who received NA therapy (cutoff value, 4.1\u00a0log U\/mL; hazard ratio, 6.749; 95% confidence interval, 1.334\u201334.15, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and even in non\u2010cirrhosis patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Hepatitis B core\u2010related antigen was useful for understanding disease progression in CHB patients and for stratifying the risk for carcinogenesis in HBeAg\u2010negative patients receiving NA therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15563","type":"journal-article","created":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T11:39:09Z","timestamp":1622461149000},"page":"2943-2951","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Hepatitis B core\u2010related antigen predicts disease progression and hepatocellular carcinoma in hepatitis B e antigen\u2010negative chronic hepatitis B patients"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2660-6580","authenticated-orcid":false,"given":"Shun","family":"Kaneko","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Musashino Red Cross Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Kurosaki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Musashino Red Cross Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6367-6396","authenticated-orcid":false,"given":"Kento","family":"Inada","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Musashino Red Cross Hospital  Tokyo 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