{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T20:54:46Z","timestamp":1759179286246,"version":"3.40.5"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","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":[[2021,1]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Recently, serum hepatitis B virus (HBV)\u2010RNA has been reported to be detectable even when HBV particle production is inhibited by nucleot(s)ide analogues (NAs). However, the dynamics of the HBV\u2010RNA sequence compared with those of HBV\u2010DNA during the emergence of antiviral resistance are yet to be elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>First, we quantified serum HBV\u2010RNA in 181 infected patients, and its relationships with clinical characteristics as well as HBV markers were investigated. Next, we undertook simultaneous deep sequencing of HBV\u2010RNA\/HBV\u2010DNA and their dynamics among four patients receiving NA therapy who were experiencing viral breakthrough.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum HBV\u2010RNA was detected in 25% (31\/123) of cases among patients with HBV without NAs, and the detection rate was significantly high in hepatitis B e antigen\u2010positive cases with high viral activity. In patients with chronic hepatitis, hepatitis B core\u2010related antigen was significantly correlated with serum HBV\u2010RNA irrespective of NA use. In the analysis of the four patients experiencing viral breakthrough, no NA resistance mutation was detected in the serum HBV\u2010RNA immediately before the breakthrough. However, NA\u2010resistant sequences appeared at the rates of 0%, 3%, 14%, and 100%, and the NA\u2010resistant HBV\u2010RNA sequence rate was correlated with the peak HBV\u2010DNA titer multiplied by the HBV\u2010DNA detection duration during the breakthrough (R<jats:sup>2<\/jats:sup>\u2009=\u20090.978) observed before redisappearance of HBV\u2010DNA following the addition of new NA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Serum HBV\u2010RNA could reflect the transcriptional activity of covalently closed circular DNA and hepatitis B core\u2010related antigen. The dynamics of HBV\u2010RNA could help understanding of the turnover process of HBV covalently closed circular DNA in the liver.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13574","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:53:38Z","timestamp":1600822418000},"page":"39-50","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Deep sequencing analysis of serum hepatitis B virus\u2010RNA during nucleot(s)ide analogue therapy"],"prefix":"10.1111","volume":"51","author":[{"given":"Shuya","family":"Matsuda","sequence":"first","affiliation":[{"name":"First Department of Internal Medicine, Faculty of Medicine University of Yamanashi  Yamanashi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-9472","authenticated-orcid":false,"given":"Shinya","family":"Maekawa","sequence":"additional","affiliation":[{"name":"First Department 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