{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T22:58:26Z","timestamp":1783465106166,"version":"3.55.0"},"reference-count":168,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Hepatitis B (HB) remains a global public health challenge, imposing significant burdens on patients and society. Therapeutic strategies and novel drug development for HB continue to be a major research focus, yet current treatments fail to achieve satisfactory clinical cure rates. To address this critical gap, more effective therapeutic approaches are urgently needed. A comprehensive understanding of the hepatitis B virus (HBV) life cycle and the immunopathogenesis of persistent HBV infection, combined with innovations in drug development and delivery systems, will lead to novel strategies for treating chronic HBV infection. This review summarizes recent advances in HBV therapeutic targets, encompassing both viral life cycle and host-directed targets. We critically evaluate emerging therapeutics, including synthetic compounds, herbal medicines, and immunomodulators, along with their supporting preclinical and clinical evidence, as well as progress in drug delivery systems including liver-targeted nanoparticles, and synergistic therapeutic strategies that combine conventional and Chinese-Western medical approaches for enhanced efficacy. Through this comprehensive analysis, this review aims to provide valuable insights for clinical management of HBV and development of innovative therapies, thereby advancing the HBV treatment field. We anticipate achieving complete cure for HB in the foreseeable future.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1692924","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T06:40:55Z","timestamp":1768372855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Current status and challenges of therapeutic targets, novel drugs and delivery systems for hepatitis B: how far to our goal?"],"prefix":"10.3389","volume":"15","author":[{"given":"Yanmei","family":"Liao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwen","family":"Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.jhep.2020.10.034","article-title":"Functional reconstitution of HBV-specific CD8 T cells by in vitro polyphenol treatment in chronic hepatitis B","volume":"74","author":"Acerbi","year":"2021","journal-title":"J. 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