{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T22:36:19Z","timestamp":1790548579358,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T00:00:00Z","timestamp":1609113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic hepatitis B virus (HBV) infection is a major global health problem. It can cause progressive liver fibrosis leading to cirrhosis with end-stage liver disease, and a markedly increased risk of hepatocellular carcinoma. In the last two decades, substantial progress has been made in the treatment of chronic hepatitis, B. However, HBV is often reactivated after stopping nucloes(t)ide analogues because antivirals alone do not directly target covalently closed circular DNA, which is the template for all viral RNAs. Therefore, although currently available antiviral therapies achieve suppression of HBV replication in the majority of patients, hepatitis B surface antigen (HBsAg) loss and seroconversion is rarely achieved despite long-term antiviral treatment (HBsAg loss of less than 10% in 5 years). Various clinical trials of agents that interrupt the HBV life cycle in hepatocytes have been conducted. Potential treatment strategies and new agents are emerging as HBV cure. A combination of current and new anti-HBV agents may increase the rate of HBsAg seroclearance; thus, optimized regimens must be validated. Here, we review the newly investigated therapeutic compounds and the results of preclinical and\/or clinical trials.<\/jats:p>","DOI":"10.3390\/ijms22010213","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T10:33:56Z","timestamp":1609151636000},"page":"213","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Hepatitis B Virus Cure: Targets and Future Therapies"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3552-3560","authenticated-orcid":false,"given":"Hye Won","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2371-0967","authenticated-orcid":false,"given":"Jae Seung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hoon","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Institute of Gastroenterology, College of Medicine, Yonsei University, Seoul 03722, Korea"},{"name":"Yonsei Liver Center, Severance Hospital, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1136\/gutjnl-2015-309809","article-title":"HBV cccDNA: Viral persistence reservoir and key obstacle for a cure of chronic hepatitis, B","volume":"64","author":"Nassal","year":"2015","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1002\/hep.28025","article-title":"Present and future therapies of hepatitis B: From discovery to cure","volume":"62","author":"Liang","year":"2015","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.virol.2015.02.031","article-title":"Molecular biology of hepatitis B virus infection","volume":"479","author":"Seeger","year":"2015","journal-title":"Virology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e00049","DOI":"10.7554\/eLife.00049","article-title":"Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus","volume":"1","author":"Yan","year":"2012","journal-title":"elife"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5841","DOI":"10.1128\/JVI.00096-07","article-title":"Infectivity determinants of the hepatitis B virus pre-S domain are confined to the N-terminal 75 amino acid residues","volume":"81","author":"Blanchet","year":"2007","journal-title":"J. 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