{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:50:54Z","timestamp":1791071454677,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004326","name":"Bayer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"publisher"}]},{"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":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Studies have shown a higher risk of hepatocellular carcinoma (HCC) with higher baseline serum hepatitis B virus (HBV) DNA levels in chronic hepatitis B (CHB) patients. However, the association between very high HBV DNA levels (&gt;6 log<jats:sub>10<\/jats:sub> IU\/mL) and HCC risk remains unclear, especially in middle\u2010aged and old HBeAg\u2010positive patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To identify the association between broad\u2010range HBV DNA levels and HCC risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a historical cohort study in Korea involving 6949 non\u2010cirrhotic, treatment\u2010na\u00efve CHB patients with alanine aminotransferase (ALT) &lt;2\u00d7 upper limit of normal for &gt;1\u00a0year. HBV DNA was &gt;6 log<jats:sub>10<\/jats:sub> IU\/mL in 2029 (29.2%) patients. Follow\u2010up was censored when the antiviral therapy was initiated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age of the patients was 45\u00a0years. During 8.0\u00a0years of median follow\u2010up, 363 patients (5.2%) developed HCC. By multivariable Cox regression analysis, HCC risk was highest with baseline HBV DNA levels of 6\u20107 log<jats:sub>10<\/jats:sub> IU\/mL (adjusted hazard ratio [aHR] 4.98; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), and lowest with &gt;8 log<jats:sub>10<\/jats:sub> IU\/mL (aHR 0.90; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.71) and \u22644 log<jats:sub>10<\/jats:sub> IU\/mL (aHR 1.00; reference), which was independent of other predictive factors. The similar association between HBV DNA levels and HCC risk was consistently observed in all age subgroups (age &lt;40, 40\u201049 and\u00a0\u2265\u00a050\u00a0years).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HCC risk was highest with moderate serum HBV DNA levels of 6\u20107 log<jats:sub>10<\/jats:sub> IU\/mL in CHB patients without significant ALT elevation. Extending treatment indication to CHB patients with moderate levels of HBV DNA may be considered to further prevent HCC, regardless of ALT levels.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15725","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T05:55:49Z","timestamp":1586930149000},"page":"1169-1179","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Moderate levels of serum hepatitis B virus DNA are associated with the highest risk of hepatocellular carcinoma in chronic hepatitis B patients"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5002-0822","authenticated-orcid":false,"given":"Gi\u2010Ae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Liver Center Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea"},{"name":"Department of Internal Medicine Kyung Hee 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Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-577X","authenticated-orcid":false,"given":"Young\u2010Suk","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Liver Center Asan Medical Center University of Ulsan College of Medicine Seoul Republic of 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