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Serum hepatitis B core\u2010related antigen (HBcrAg) is a new biomarker for intrahepatic templates for HBV replication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To explore whether a high HBcrAg level is associated with increased risk of cirrhosis, especially in patients with intermediate viral load (HBV DNA 2000\u201019\u00a0999\u00a0IU\/mL) due to their moderate risk of disease progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 1673 treatment\u2010na\u00efve, non\u2010cirrhotic patients with negative hepatitis B e antigen (HBeAg) and alanine aminotransferase (ALT) level &lt;40\u00a0U\/L at baseline were enrolled. We explored the relationship between baseline levels of HBcrAg and cirrhosis development in all patients, and whether a higher HBcrAg level (&lt;10 vs \u226510\u00a0KU\/mL) was associated with an increased risk of disease progression in those with intermediate viral load.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 1673 patients, 104 developed cirrhosis after a mean follow\u2010up of 15.9\u00a0years. Higher HBcrAg levels were associated with increased incidence of cirrhosis, cirrhosis\u2010related complications, and liver\u2010related death. In 445 patients with intermediate viral load, the cirrhosis risk stratified by HBcrAg level of 10 KU\/mL yielded a hazard ratio of 3.22 (95% CI: 1.61\u20106.47). The risk stratification remained significant when exploring other pre\u2010cirrhosis endpoints, including HBeAg\u2010negative hepatitis, hepatitis flare, and HBV DNA &gt;20\u00a0000\u00a0IU\/mL after 3\u00a0years of follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In HBeAg\u2010negative patients with normal ALT levels, higher HBcrAg levels are associated with increased risk of cirrhosis. Among those with intermediate viral load, HBcrAg &lt;10\u00a0KU\/mL defines a low\u2010risk group for disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.16266","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T17:45:21Z","timestamp":1693590321000},"page":"908-918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Serum hepatitis B core\u2010related antigen level stratifies risk of disease progression in chronic hepatitis B patients with intermediate viral load"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0420-8311","authenticated-orcid":false,"given":"Tai\u2010Chung","family":"Tseng","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan"},{"name":"Hepatitis Research Center National Taiwan University Hospital Taipei 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