{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:26:39Z","timestamp":1788614799881,"version":"build-2803163510"},"reference-count":107,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T00:00:00Z","timestamp":1656201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Research Program on Hepatitis from the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22fk0310518"],"award-info":[{"award-number":["22fk0310518"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Research Program on Hepatitis from the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21K07897"],"award-info":[{"award-number":["21K07897"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Research Program on Hepatitis from the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20K16996"],"award-info":[{"award-number":["20K16996"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education, Culture, Sports, Science, and Technology","award":["22fk0310518"],"award-info":[{"award-number":["22fk0310518"]}]},{"name":"Ministry of Education, Culture, Sports, Science, and Technology","award":["21K07897"],"award-info":[{"award-number":["21K07897"]}]},{"name":"Ministry of Education, Culture, Sports, Science, and Technology","award":["20K16996"],"award-info":[{"award-number":["20K16996"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis B virus (HBV) causes acute and, most importantly, chronic hepatitis B worldwide. Antiviral treatments have been developed to reduce viral loads but few patients with chronic hepatitis B (CHB) achieve a functional cure. The development of new therapeutic agents is desirable. Recently, many novel agents have been developed, including drugs targeting HBV-DNA and HBV-RNA. This review provides an overview of the developmental status of these drugs, especially direct acting antiviral agents (DAAs). Serological biomarkers of HBV infection are essential for predicting the clinical course of CHB. It is also important to determine the amount and activity of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. Hepatitis B core-associated antigen (HBcrAg) is a new HBV marker that has an important role in reflecting cccDNA in CHB, because it is associated with hepatic cccDNA, as well as serum HBV DNA. The highly sensitive HBcrAg (iTACT-HBcrAg) assay could be a very sensitive HBV activation marker and an alternative to HBV DNA testing for monitoring reactivation. Many of the drugs currently in clinical trials have shown efficacy in reducing hepatitis B surface antigen (HBsAg) levels. Combination therapies with DAAs and boost immune response are also under development; finding the best combinations will be important for therapeutic development.<\/jats:p>","DOI":"10.3390\/v14071393","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T22:50:23Z","timestamp":1656283823000},"page":"1393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Drug Discovery Study Aimed at a Functional Cure for HBV"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8990-9496","authenticated-orcid":false,"given":"Takehisa","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9164-9152","authenticated-orcid":false,"given":"Sanae","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-6966","authenticated-orcid":false,"given":"Yasuhito","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.jhep.2011.12.032","article-title":"Peginterferon-\u03b1 does not improve early peripheral blood HBV-specific T-cell responses in HBeAg-negative chronic hepatitis","volume":"56","author":"Penna","year":"2012","journal-title":"J. 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