{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:12:07Z","timestamp":1791774727839,"version":"4.3.4"},"reference-count":153,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis B virus (HBV) infection is a major global health problem causing acute and chronic liver disease that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). HBV covalently closed circular DNA (cccDNA) is essential for viral replication and the establishment of a persistent infection. Integrated HBV DNA represents another stable form of viral DNA regularly observed in the livers of infected patients. HBV DNA integration into the host genome occurs early after HBV infection. It is a common occurrence during the HBV life cycle, and it has been detected in all the phases of chronic infection. HBV DNA integration has long been considered to be the main contributor to liver tumorigenesis. The recent development of highly sensitive detection methods and research models has led to the clarification of some molecular and pathogenic aspects of HBV integration. Though HBV integration does not lead to replication-competent transcripts, it can act as a stable source of viral RNA and proteins, which may contribute in determining HBV-specific T-cell exhaustion and favoring virus persistence. The relationship between HBV DNA integration and the immune response in the liver microenvironment might be closely related to the development and progression of HBV-related diseases. While many new antiviral agents aimed at cccDNA elimination or silencing have been developed, integrated HBV DNA remains a difficult therapeutic challenge.<\/jats:p>","DOI":"10.3390\/v13030368","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T09:47:20Z","timestamp":1614332840000},"page":"368","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["HBV-Integration Studies in the Clinic: Role in the Natural History of Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Teresa","family":"Pollicino","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Hepatology, Department of Human Pathology, University Hospital \u201cG. Martino\u201d of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Caminiti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Hepatology, Department of Human Pathology, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"ref_1","unstructured":"WHO (World Health Organization) (2019, April 04). Global Hepatitis Report 2017. Available online: https:\/\/www.who.int\/hepatitis\/publications\/global-hepatitis-report2017\/en\/."},{"key":"ref_2","unstructured":"The Polaris Observatory Collaborators (2018). Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study. Lancet Gastroenterol. Hepatol., 3, 383\u2013403."},{"key":"ref_3","unstructured":"GBD 2016 Disease and Injury Incidence and Prevalence Collaborators (2017). 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