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Complete cure is characterized by the HBV elimination from the body\u00a0and is the goal of the chronic hepatitis B treatment, which once achieved, will enable the hepatitis B elimination. This, today, has been a scientific challenge. The difficulty in achieving a complete cure is due to the indefinite maintenance of a covalently closed episomal circular DNA (cccDNA) reservoir and the maintenance and persistence of an insufficient and dysfunctional immune response in chronically infected patients. Among the measures adopted to eliminate hepatitis B, two have the potential to directly interfere with the virus cycle, but with limited effect on HBV control. These are conventional vaccines\u2014blocking transmission and antiviral therapy\u2014inhibiting replication. Vaccines, despite their effectiveness in protecting against horizontal transmission and preventing mother\u2010to\u2010child vertical transmission, have no effect on chronic infection or potential to eliminate the virus. Treatment with antivirals suppresses viral replication, but has no curative effect, as it has no action against cccDNA. Therapeutic vaccines comprise an additional approach in the chronic infection treatment, however, they have only a modest effect on the immune system, enhancing it temporarily.\u00a0This manuscript aims to address (1)\u00a0the cccDNA persistence in the hepatocyte nucleus and the immune response dysfunction in chronically infected individuals\u00a0as two primary factors that have hampered the treatment and HBV elimination from the human body; (2)\u00a0the limitations of antiviral therapy and therapeutic vaccines, as strategies to control hepatitis B; and (3)\u00a0the possibly promising therapeutic approaches for the complete cure and elimination of hepatitis B.<\/jats:p>","DOI":"10.1002\/med.22030","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T05:29:24Z","timestamp":1711430964000},"page":"2015-2034","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Elimination of the hepatitis B virus: A goal, a challenge"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8909-9091","authenticated-orcid":false,"given":"Rob\u00e9rio Amorim de Almeida","family":"Pond\u00e9","sequence":"first","affiliation":[{"name":"Secretaria de Estado da Sa\u00fade\u2010SES Superintend\u00eancia de Vigil\u00e2ncia em Sa\u00fade\u2010SUVISA\/GO, Ger\u00eancia de Vigil\u00e2ncia Epidemiol\u00f3gica de Doen\u00e7as Transmiss\u00edveis\u2010GVEDT\/Coordena\u00e7\u00e3o de An\u00e1lises e Pesquisas\u2010CAP Goi\u00e2nia Goi\u00e1s Brazil"},{"name":"Department of Microbiology, Laboratory of Human Virology, Institute of Tropical Pathology and Public Health Federal University of Goi\u00e1s Goi\u00e2nia Goi\u00e1s Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-4979","authenticated-orcid":false,"given":"Guilherme de Sousa Pond\u00e9","family":"Amorim","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Evangelical University of Goi\u00e1s An\u00e1polis Goi\u00e1s Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"WHO 2017Geneva.https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/255016\/9789241565455-eng.pdf;jsessionid=E755A573714A211D864D6FECC4B18D47?sequence=1"},{"key":"e_1_2_10_3_1","unstructured":"WHO 2022a. 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