{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:19:06Z","timestamp":1792804746160,"version":"4.5.0"},"reference-count":224,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,4]],"date-time":"2023-03-04T00:00:00Z","timestamp":1677888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Center for Infection Research","award":["HI858\/12-4"],"award-info":[{"award-number":["HI858\/12-4"]}],"id":[{"id":"https:\/\/ror.org\/028s4q594","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Loewe Center DRUID","award":["HI858\/12-4"],"award-info":[{"award-number":["HI858\/12-4"]}]},{"name":"German Research Foundation","award":["HI858\/12-4"],"award-info":[{"award-number":["HI858\/12-4"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The hepatitis B virus (HBV) counts as a major global health problem, as it presents a significant causative factor for liver-related morbidity and mortality. The development of hepatocellular carcinomas (HCC) as a characteristic of a persistent, chronic infection could be caused, among others, by the pleiotropic function of the viral regulatory protein HBx. The latter is known to modulate an onset of cellular and viral signaling processes with emerging influence in liver pathogenesis. However, the flexible and multifunctional nature of HBx impedes the fundamental understanding of related mechanisms and the development of associated diseases, and has even led to partial controversial results in the past. Based on the cellular distribution of HBx\u2014nuclear-, cytoplasmic- or mitochondria-associated\u2014this review encompasses the current knowledge and previous investigations of HBx in context of cellular signaling pathways and HBV-associated pathogenesis. In addition, particular focus is set on the clinical relevance and potential novel therapeutic applications in the context of HBx.<\/jats:p>","DOI":"10.3390\/ijms24054964","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T03:49:08Z","timestamp":1678074548000},"page":"4964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis"],"prefix":"10.3390","volume":"24","author":[{"given":"Anja","family":"Schollmeier","sequence":"first","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8799-7565","authenticated-orcid":false,"given":"Mirco","family":"Glitscher","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3020-9564","authenticated-orcid":false,"given":"Eberhard","family":"Hildt","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Vos","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5427","DOI":"10.3748\/wjg.v20.i18.5427","article-title":"Hepatitis B virus genotypes: Global distribution and clinical importance","volume":"20","author":"Sunbul","year":"2014","journal-title":"World J. 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