{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T06:40:03Z","timestamp":1767163203216,"version":"build-2238731810"},"reference-count":33,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T00:00:00Z","timestamp":1711065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Patients with chronic hepatitis\u00a0B virus (HBV) infection experiencing viral breakthrough (BTH) or partial response (PR) during lamivudine (LAM) or entecavir hydrate (ETV) administration often took ETV plus tenofovir alafenamide fumarate (TAF) due to the emergence of a drug\u2010resistance mutation. However, in patients lacking drug\u2010resistance mutation against TAF, sufficient antiviral effects may be achievable with TAF monotherapy. We assessed the drug\u2010resistance profile through nucleotide sequences of HBV pregenome RNA, and subsequently changed to TAF monotherapy from ETV plus TAF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective study included 25 patients with serum HBV\u2010DNA below 20\u00a0IU\/mL under ETV plus TAF administration. Pregenome RNA nucleotide sequences of HBV in the sera were analyzed using direct sequencing and deep sequencing. ETV was discontinued in patients without rtA194T and rtS106C\u00a0+\u00a0rtH126Y +\u00a0rtD134E +\u00a0rtL269I quadruple mutations in direct sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>LAM\u2010PR, LAM\u2010BTH, ETV\u2010PR, and ETV\u2010BTH were observed in 1, 16, 7, and 1 patient(s), respectively. Pregenome RNA nucleotide sequences were analyzable in 20 patients. Among the 12 patients classified as LAM\u2010BTH, six patients showed rtL180M\u00a0+\u00a0rtM204V\/I in direct sequencing, and one patient showed minor clones containing rtL180M\u00a0+\u00a0rtM204V\u00a0+\u00a0A194T in deep sequencing at a frequency of 0.3%. In the six patients classified as ETV\u2010PR, one patient harbored rtM204I. No clones showing rtS106C\u00a0+\u00a0rtH126Y\u00a0+\u00a0rtD134E\u00a0+\u00a0rtL269I quadruple mutation were detected in deep sequencing. Subsequently, ETV was discontinued, and serum HBV\u2010DNA remained undetectable up to 48\u00a0weeks in all patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Patients receiving ETV plus TAF due to partial response or BTH during initial LAM or ETV administration were able to safely transition to TAF monotherapy based on nucleotide sequences of HBV pregenome RNA in the sera.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hepr.14036","type":"journal-article","created":{"date-parts":[[2024,3,22]],"date-time":"2024-03-22T12:15:14Z","timestamp":1711109714000},"page":"877-887","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Switching from combination therapy with entecavir hydrate plus tenofovir alafenamide fumarate to tenofovir alafenamide fumarate monotherapy in patients with chronic hepatitis\u00a0B based on nucleotide sequences of hepatitis\u00a0B virus pregenome RNA"],"prefix":"10.1111","volume":"54","author":[{"given":"Shunsuke","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Faculty of Medicine Saitama Medical University  Iruma\u2010gun Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6012-0915","authenticated-orcid":false,"given":"Yoshihito","family":"Uchida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Faculty of Medicine Saitama Medical University  Iruma\u2010gun Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun\u2010Ichi","family":"Kouyama","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Faculty of Medicine Saitama Medical University  Iruma\u2010gun 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