{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:16:52Z","timestamp":1790713012358,"version":"4.1.0"},"reference-count":223,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Hepatitis B Virus (HBV) is an Old World virus with a high mutation rate, which puts its origins in Africa alongside the origins of Homo sapiens, and is a member of the Hepadnaviridae family that is characterized by a unique viral replication cycle. It targets human hepatocytes and can lead to chronic HBV infection either after acute infection via horizontal transmission usually during infancy or childhood or via maternal\u2013fetal transmission. HBV has been found in ~85% of HBV-related Hepatocellular Carcinomas (HCC), and it can integrate the whole or part of its genome into the host genomic DNA. The molecular mechanisms involved in the HBV DNA integration is not yet clear; thus, multiple models have been described with respect to either the relaxed-circular DNA (rcDNA) or the double-stranded linear DNA (dslDNA) of HBV. Various genes have been found to be affected by HBV DNA integration, including cell-proliferation-related genes, oncogenes and long non-coding RNA genes (lincRNAs). The present review summarizes the advances in the research of HBV DNA integration, focusing on the evolutionary and molecular side of the integration events along with the arising clinical aspects in the light of WHO\u2019s commitment to eliminate HBV and viral hepatitis by 2030.<\/jats:p>","DOI":"10.3390\/microorganisms9081787","type":"journal-article","created":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T10:24:17Z","timestamp":1629714257000},"page":"1787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["Hepatitis B Virus DNA Integration, Chronic Infections and Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2829-1642","authenticated-orcid":false,"given":"Maria","family":"Bousali","sequence":"first","affiliation":[{"name":"Bioinformatics and Applied Genomics Unit, Department of Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3518-4060","authenticated-orcid":false,"given":"George","family":"Papatheodoridis","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, \u201cLaiko\u201d General Hospital of Athens, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6167-7152","authenticated-orcid":false,"given":"Dimitrios","family":"Paraskevis","sequence":"additional","affiliation":[{"name":"Department of Hygiene Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0841-9159","authenticated-orcid":false,"given":"Timokratis","family":"Karamitros","sequence":"additional","affiliation":[{"name":"Bioinformatics and Applied Genomics Unit, Department of Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece"},{"name":"Laboratory of Medical Microbiology, Department of Microbiology, Hellenic Pasteur Institute, 11521 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1001\/jama.1984.03350020054026","article-title":"A \u201cNew\u201d Antigen in Leukemia Sera","volume":"252","author":"Blumberg","year":"1984","journal-title":"JAMA J. Am. Med. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.antiviral.2016.04.012","article-title":"A historical perspective on the discovery and elucidation of the hepatitis B virus","volume":"131","author":"Block","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/BF01929017","article-title":"Ueber das Vorkommen und den Nachweis des hepatogenen, insbesondere des katarrhalischen Icterus","volume":"32","author":"Gruber","year":"1865","journal-title":"Arch. Pathol. Anat. Physiol. Klin. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1007\/s11605-007-0281-1","article-title":"Jaundice in the hippocratic corpus","volume":"11","author":"Papavramidou","year":"2007","journal-title":"J. Gastrointest. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0002-9343(46)90017-4","article-title":"Homologous serum hepatitis and infectious (epidemic) hepatitis: Studies in volunteers bearing on immunological and other characteristics of the etiological agents","volume":"1","author":"Neefe","year":"1946","journal-title":"Am. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1097\/00005792-194209010-00001","article-title":"The natural history of laennec\u2019s cirrhosis of the liver an Analysis of 386 CASES","volume":"21","author":"Ratnoff","year":"1942","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Millman, I., Eisenstein, T., and Blumberg, B.S. (1984). The Development of the Hepatitis B Vaccine, Springer.","DOI":"10.1007\/978-1-4899-0369-3"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJM198612183152503","article-title":"Treatment of Chronic Non-A, Non-B Hepatitis with Recombinant Human Alpha Interferon","volume":"315","author":"Hoofnagle","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1056\/NEJM199807093390201","article-title":"A One-Year Trial of Lamivudine for Chronic Hepatitis B","volume":"339","author":"Lai","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1056\/NEJM198110293051807","article-title":"Integration of Hepatitis B Virus DNA into the Genome of Liver Cells in Chronic Liver Disease and Hepatocellular Carcinoma","volume":"305","author":"Shafritz","year":"1981","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0092-8674(83)90152-6","article-title":"Integration of hepatitis B virus DNA: Evidence for integration in the single-stranded gap","volume":"34","author":"Koshy","year":"1983","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/286533a0","article-title":"Presence of integrated hepatitis B virus DNA sequences in cellular DNA of human hepatocellular carcinoma","volume":"286","author":"Brechot","year":"1980","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/286531a0","article-title":"Identification of integrated hepatitis B virus DNA and expression of viral RNA in an HBsAg-producing human hepatocellular carcinoma cell line","volume":"286","author":"Chakraborty","year":"1980","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.jhep.2005.02.005","article-title":"The role of hepatitis B virus integrations in the pathogenesis of human hepatocellular carcinoma","volume":"42","author":"Guerrero","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1136\/gut.2004.054452","article-title":"Large scaled analysis of hepatitis B virus (HBV) DNA integration in HBV related hepatocellular carcinomas","volume":"54","author":"Murakami","year":"2005","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/humu.20701","article-title":"Integration of hepatitis B virus DNA into the myeloid\/lymphoid or mixed-lineage leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular carcinoma","volume":"29","author":"Saigo","year":"2008","journal-title":"Hum. Mutat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3813","DOI":"10.1038\/sj.onc.1206528","article-title":"Integrations of the hepatitis B virus (HBV) and human papillomavirus (HPV) into the human telomerase reverse transcriptase (hTERT) gene in liver and cervical cancers","volume":"22","author":"Ferber","year":"2003","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1038\/sj.onc.1206492","article-title":"Hepatitis B virus-related insertional mutagenesis occurs frequently in human liver cancers and recurrently targets human telomerase gene","volume":"22","author":"Saigo","year":"2003","journal-title":"Oncogene"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6233","DOI":"10.1038\/sj.onc.1204835","article-title":"Identification of human cancer-related genes by naturally occurring hepatitis B virus DNA tagging","volume":"20","author":"Gozuacik","year":"2001","journal-title":"Oncogene"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: A modelling study","volume":"3","author":"Gamkrelidze","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4959","DOI":"10.3748\/wjg.v24.i44.4959","article-title":"Hepatitis elimination by 2030: Progress and challenges","volume":"24","author":"Waheed","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e25050","DOI":"10.1002\/jia2.25050","article-title":"How far are we from viral hepatitis elimination service coverage targets?","volume":"21","author":"Hutin","year":"2018","journal-title":"J. Int. AIDS Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-68021-2","article-title":"A nationwide cross-sectional survey on hepatitis B and C screening among workers in Japan","volume":"10","author":"Tatemichi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_24","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\u2013480","author":"Seeger","year":"2015","journal-title":"Virology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/s41575-020-0296-6","article-title":"The evolution and clinical impact of hepatitis B virus genome diversity","volume":"17","author":"Revill","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/hep.26079","article-title":"Dating the origin and dispersal of hepatitis B virus infection in humans and primates","volume":"57","author":"Paraskevis","year":"2013","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ympev.2015.07.010","article-title":"Dating the origin of hepatitis B virus reveals higher substitution rate and adaptation on the branch leading to F\/H genotypes","volume":"93","author":"Paraskevis","year":"2015","journal-title":"Mol. Phylogenet. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/ng.2744","article-title":"Out-of-Africa migration and Neolithic coexpansion of Mycobacterium tuberculosis with modern humans","volume":"45","author":"Comas","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/nature05562","article-title":"An African origin for the intimate association between humans and Helicobacter pylori","volume":"445","author":"Linz","year":"2007","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1002\/hep.25852","article-title":"Tracing hepatitis B virus to the 16th century in a Korean mummy","volume":"56","author":"Kim","year":"2012","journal-title":"Hepatology"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Patterson Ross, Z., Klunk, J., Fornaciari, G., Giuffra, V., Duch\u00eane, S., Duggan, A.T., Poinar, D., Douglas, M.W., Eden, J.S., and Holmes, E.C. (2018). The paradox of HBV evolution as revealed from a 16th century mummy. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006887"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/s41586-018-0097-z","article-title":"Ancient hepatitis B viruses from the Bronze Age to the Medieval period","volume":"557","author":"Jones","year":"2018","journal-title":"Nature"},{"key":"ref_33","first-page":"1","article-title":"Neolithic and medieval virus genomes reveal complex evolution of hepatitis B","volume":"7","author":"Susat","year":"2018","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7920","DOI":"10.1128\/JVI.00832-16","article-title":"Distinct Viral Lineages from Fish and Amphibians Reveal the Complex Evolutionary History of Hepadnaviruses","volume":"90","author":"Dill","year":"2016","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"a021360","DOI":"10.1101\/cshperspect.a021360","article-title":"Origins and Evolution of Hepatitis B Virus and Hepatitis D Virus","volume":"6","author":"Littlejohn","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Velkov, S., Ott, J.J., Protzer, U., and Michler, T. (2018). The global hepatitis B virus genotype distribution approximated from available genotyping data. Genes, 9.","DOI":"10.3390\/genes9100495"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000360947","article-title":"Genotypes and genetic variability of hepatitis B virus","volume":"57","author":"Kramvis","year":"2014","journal-title":"Intervirology"},{"key":"ref_39","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. Gastroenterol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1128\/MMBR.05023-11","article-title":"Viral quasispecies evolution","volume":"76","author":"Domingo","year":"2012","journal-title":"Microbiol. Mol. Biol. Rev. MMBR"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Raihan, R., Akbar, S.M.F., Mahtab, M.A., Takahashi, K., Masumoto, J., Tabassum, S., Tee, K.K., and Mohamed, R.B. (2019). Genomic analysis of Hepatitis B virus and its association with disease manifestations in Bangladesh. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218744"},{"key":"ref_42","first-page":"1741","article-title":"Detection of HBV Genotype C in Hepatocellular Carcinoma Patients from North East India: A Brief Report","volume":"19","author":"Sarma","year":"2018","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1053\/j.gastro.2007.08.010","article-title":"Clearance of Hepatitis B e Antigen in Patients with Chronic Hepatitis B and Genotypes A, B, C, D, and F","volume":"133","author":"Livingston","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jhep.2007.11.011","article-title":"Natural history of chronic hepatitis B: Special emphasis on disease progression and prognostic factors","volume":"48","author":"Giovanna","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev.pathol.1.110304.100230","article-title":"Immunobiology and pathogenesis of viral hepatitis","volume":"1","author":"Guidotti","year":"2006","journal-title":"Annu. Rev. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104816","DOI":"10.1016\/j.antiviral.2020.104816","article-title":"Mechanisms of HBV immune evasion","volume":"179","author":"Kuipery","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/hep.22898","article-title":"The natural history of chronic hepatitis B virus infection","volume":"49","author":"McMahon","year":"2009","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/hep.510300109","article-title":"The long-term course of chronic hepatitis B","volume":"30","author":"Vaccaro","year":"1999","journal-title":"Hepatology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1053\/j.gastro.2005.11.016","article-title":"Predicting cirrhosis risk based on the level of circulating hepatitis B viral load","volume":"130","author":"Iloeje","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"European Association For The Study Of The Liver (2017). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol., 67, 370\u2013398.","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/hep.21724","article-title":"Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase","volume":"46","author":"Hui","year":"2007","journal-title":"Hepatology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1055\/s-2005-915644","article-title":"Epidemiology and natural history of hepatitis B","volume":"25","author":"McMahon","year":"2005","journal-title":"Semin. Liver Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/hep.21513","article-title":"Chronic hepatitis B","volume":"45","author":"Lok","year":"2007","journal-title":"Hepatology (Baltimore Md.)"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.antiviral.2015.06.008","article-title":"Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities","volume":"121","author":"Gish","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"a021345","DOI":"10.1101\/cshperspect.a021345","article-title":"Viral hepatitis: Past and future of HBV and HDV","volume":"5","author":"Thomas","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Iannacone, M., and Guidotti, L.G. (2021). Immunobiology and pathogenesis of hepatitis B virus infection. Nat. Rev. Immunol.","DOI":"10.1038\/s41577-021-00549-4"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/s41573-019-0037-0","article-title":"Therapeutic strategies for hepatitis B virus infection: Towards a cure","volume":"18","author":"Fanning","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Hu, J., and Liu, K. (2017). Complete and incomplete hepatitis B virus particles: Formation, function, and application. Viruses, 9.","DOI":"10.3390\/v9030056"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"104925","DOI":"10.1016\/j.antiviral.2020.104925","article-title":"Hepatitis B virus biology and life cycle","volume":"182","author":"Tsukuda","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/S0140-6736(70)90926-8","article-title":"Virus-like particles in serum of patients with Australia-antigen-associated hepatitis","volume":"1","author":"Dane","year":"1970","journal-title":"Lancet"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1111\/jvh.12361","article-title":"Genome-free hepatitis B virion levels in patient sera as a potential marker to monitor response to antiviral therapy","volume":"22","author":"Luckenbaugh","year":"2015","journal-title":"J. Viral Hepat."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"9786","DOI":"10.1128\/JVI.79.15.9786-9798.2005","article-title":"Mapping of the Hepatitis B Virus Pre-S1 Domain Involved in Receptor Recognition","volume":"79","author":"Barrera","year":"2005","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1128\/JVI.02303-05","article-title":"Lipid-Mediated Introduction of Hepatitis B Virus Capsids into Nonsusceptible Cells Allows Highly Efficient Replication and Facilitates the Study of Early Infection Events","volume":"80","author":"Rabe","year":"2006","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1016\/j.jhep.2016.02.008","article-title":"Intracellular transport and egress of hepatitis B virus","volume":"64","author":"Blondot","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_65","first-page":"E4244","article-title":"Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses","volume":"111","author":"Wingert","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Cui, X., McAllister, R., Boregowda, R., Sohn, J.A., Ledesma, F.C., Caldecott, K.W., Seeger, C., and Hu, J. (2015). Does tyrosyl DNA phosphodiesterase-2 play a role in hepatitis B virus genome repair?. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128401"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Qi, Y., Gao, Z., Xu, G., Peng, B., Liu, C., Yan, H., Yao, Q., Sun, G., Liu, Y., and Tang, D. (2016). DNA Polymerase \u03ba Is a Key Cellular Factor for the Formation of Covalently Closed Circular DNA of Hepatitis B Virus. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005893"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Tang, L., Sheraz, M., McGrane, M., Chang, J., and Guo, J.T. (2019). DNA Polymerase alpha is essential for intracellular amplification of hepatitis B virus covalently closed circular DNA. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007742"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Long, Q., Yan, R., Hu, J., Cai, D., Mitra, B., Kim, E.S., Marchetti, A., Zhang, H., Wang, S., and Liu, Y. (2017). The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006784"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kitamura, K., Que, L., Shimadu, M., Koura, M., Ishihara, Y., Wakae, K., Nakamura, T., Watashi, K., Wakita, T., and Muramatsu, M. (2018). Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007124"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/0092-8674(80)90443-2","article-title":"Hepatitis B virus contains protein attached to the 5\u2019 terminus of its complete DNA strand","volume":"21","author":"Gerlich","year":"1980","journal-title":"Cell"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"12472","DOI":"10.1128\/JVI.01123-07","article-title":"Characterization of the Intracellular Deproteinized Relaxed Circular DNA of Hepatitis B Virus: An Intermediate of Covalently Closed Circular DNA Formation","volume":"81","author":"Guo","year":"2007","journal-title":"J. Virol."},{"key":"ref_73","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_74","first-page":"1766","article-title":"Transcription of hepatitis B virus by RNA polymerase II","volume":"3","author":"Rall","year":"1983","journal-title":"Mol. Cell. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9710","DOI":"10.1128\/JVI.73.12.9710-9717.1999","article-title":"Integration of hepadnavirus DNA in infected liver: Evidence for a linear precursor","volume":"73","author":"Yang","year":"1999","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1073\/pnas.0409332102","article-title":"Clonal expansion of hepatocytes during chronic woodchuck hepatitis virus infection","volume":"102","author":"Mason","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1073\/pnas.0307422100","article-title":"Residual integrated viral DNA after hepadnavirus clearance by nucleoside analog therapy","volume":"101","author":"Summers","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8308","DOI":"10.1128\/JVI.00833-10","article-title":"Clonal expansion of normal-appearing human hepatocytes during chronic hepatitis B virus infection","volume":"84","author":"Mason","year":"2010","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1111\/jvh.12380","article-title":"Clonal expansion of hepatocytes with a selective advantage occurs during all stages of chronic hepatitis B virus infection","volume":"22","author":"Tu","year":"2015","journal-title":"J. Viral Hepat."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1053\/j.gastro.2016.07.012","article-title":"HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant","volume":"151","author":"Mason","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e02007-17","DOI":"10.1128\/JVI.02007-17","article-title":"Hepatitis B Virus DNA Integration Occurs Early in the Viral Life Cycle in an In Vitro Infection Model via Sodium Taurocholate Cotransporting Polypeptide-Dependent Uptake of Enveloped Virus Particles","volume":"92","author":"Tu","year":"2018","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/ng.2295","article-title":"Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma","volume":"44","author":"Sung","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"12992","DOI":"10.1038\/ncomms12992","article-title":"Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma","volume":"7","author":"Zhao","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1101\/gr.133926.111","article-title":"The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients","volume":"22","author":"Jiang","year":"2012","journal-title":"Genome Res."},{"key":"ref_85","first-page":"100034","article-title":"Insights into Hepatitis B Virus DNA Integration-55 Years after Virus Discovery","volume":"1","author":"Zhao","year":"2020","journal-title":"Innov. States"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1073\/pnas.81.17.5350","article-title":"Specific hepatitis B virus integration in hepatocellular carcinoma DNA through a viral 11-base-pair direct repeat","volume":"81","author":"Dejean","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1002\/hep.27722","article-title":"Characterization of the genotype and integration patterns of hepatitis B virus in early- and late-onset hepatocellular carcinoma","volume":"61","author":"Yan","year":"2015","journal-title":"Hepatology"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chauhan, R., Churchill, N.D., Mulrooney-Cousins, P.M., and Michalak, T.I. (2017). Initial sites of hepadnavirus integration into host genome in human hepatocytes and in the woodchuck model of hepatitis B-associated hepatocellular carcinoma. Oncogenesis, 6.","DOI":"10.1038\/oncsis.2017.22"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8396","DOI":"10.1128\/JVI.00700-09","article-title":"Detection of Clonally Expanded Hepatocytes in Chimpanzees with Chronic Hepatitis B Virus Infection","volume":"83","author":"Mason","year":"2009","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6871","DOI":"10.1093\/nar\/12.17.6871","article-title":"The genetic organization of integrated hepatitis B virus DNA in the human hepatoma cell line PLC\/PRF\/5","volume":"12","author":"Koch","year":"1984","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1128\/jvi.61.11.3491-3498.1987","article-title":"Tight clustering of human hepatitis B virus integration sites in hepatomas near a triple-stranded region","volume":"61","author":"Shih","year":"1987","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/0042-6822(84)90231-9","article-title":"Hepatitis B virus DNA forms in nuclear and cytoplasmic fractions of infected human liver","volume":"137","author":"Miller","year":"1984","journal-title":"Virology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4458","DOI":"10.1073\/pnas.82.13.4458","article-title":"Hepatitis B virus integration in hepatocellular carcinoma DNA: Duplication of cellular flanking sequences at the integration site","volume":"82","author":"Yaginuma","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2638","DOI":"10.1128\/jvi.63.6.2638-2643.1989","article-title":"Features of two hepatitis B virus (HBV) DNA integrations suggest mechanisms of HBV integration","volume":"63","author":"Hino","year":"1989","journal-title":"J. Virol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"8338","DOI":"10.1073\/pnas.83.21.8338","article-title":"Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17;18 translocation","volume":"83","author":"Hino","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.ccr.2014.01.030","article-title":"Viral-human chimeric transcript predisposes risk to liver cancer development and progression","volume":"25","author":"Lau","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Budzinska, M.A., Shackel, N.A., Urban, S., and Tu, T. (2018). Sequence analysis of integrated hepatitis B virus DNA during HBeAg-seroconversion. Emerg. Microbes Infect., 7.","DOI":"10.1038\/s41426-018-0145-7"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.tig.2008.08.007","article-title":"MMEJ repair of double-strand breaks: Deleted sequences and alternative endings","volume":"24","author":"Mcvey","year":"2017","journal-title":"Trends Genet."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/sj.onc.1206889","article-title":"Characterization of HBV integrants in 14 hepatocellular carcinomas: Association of truncated X gene and hepatocellular carcinogenesis","volume":"23","author":"Wang","year":"2004","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"11630","DOI":"10.3748\/wjg.v20.i33.11630","article-title":"Molecular mechanism of hepatitis B virus-induced hepatocarcinogenesis","volume":"20","author":"Tarocchi","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"12725","DOI":"10.1128\/JVI.78.23.12725-12734.2004","article-title":"The enigmatic X gene of hepatitis B virus","volume":"78","author":"Bouchard","year":"2004","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1001\/jamaoncol.2017.3055","article-title":"The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015","volume":"3","author":"Akinyemiju","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1053\/jhep.2002.36780","article-title":"Risk factors for hepatocellular carcinoma: Synergism of alcohol with viral hepatitis and diabetes mellitus","volume":"36","author":"Hassan","year":"2002","journal-title":"Hepatology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/aje\/kwg041","article-title":"Incidence and cofactors of hepatitis C virus-related hepatocellular carcinoma: A prospective study of 12,008 men in Taiwan","volume":"157","author":"Sun","year":"2003","journal-title":"Am. J. Epidemiol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Jiang, S., Yang, Z., Li, W., Li, X., Wang, Y., Zhang, J., Xu, C., Chen, P.J., Hou, J., and McCrae, M.A. (2012). Re-evaluation of the Carcinogenic Significance of Hepatitis B Virus Integration in Hepatocarcinogenesis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040363"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1046\/j.1365-2893.2000.00209.x","article-title":"Frequent integration of precore\/core mutants of hepatitis B virus in human hepatocellular carcinoma tissues","volume":"7","author":"Zhong","year":"2000","journal-title":"J. Viral Hepat."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Ding, D., Lou, X., Hua, D., Yu, W., Li, L., Wang, J., Gao, F., Zhao, N., Ren, G., and Li, L. (2012). Recurrent Targeted Genes of Hepatitis B Virus in the Liver Cancer Genomes Identified by a Next-Generation Sequencing-Based Approach. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1003065"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1038\/sj.onc.1208628","article-title":"Hepatitis B virus-related insertional mutagenesis in chronic hepatitis B patients as an early drastic genetic change leading to hepatocarcinogenesis","volume":"24","author":"Minami","year":"2005","journal-title":"Oncogene"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6761","DOI":"10.1128\/jvi.65.12.6761-6764.1991","article-title":"Chromosomal sites for hepatitis B virus integration in human hepatocellular carcinoma","volume":"65","author":"Tokino","year":"1991","journal-title":"J. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"11652","DOI":"10.1073\/pnas.1635109100","article-title":"Hepatocyte turnover during resolution of a transient hepadnaviral infection","volume":"100","author":"Summers","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.canlet.2006.11.010","article-title":"Hepatitis B virus integration, fragile sites, and hepatocarcinogenesis","volume":"252","author":"Feitelson","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"D633","DOI":"10.1093\/nar\/gkz867","article-title":"VISDB: A manually curated database of viral integration sites in the human genome","volume":"48","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1093\/carcin\/bgg085","article-title":"Transcriptional regulation of the telomerase hTERT gene as a target for cellular and viral oncogenic mechanisms","volume":"24","author":"Horikawa","year":"2003","journal-title":"Carcinogenesis"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1038\/ng.2291","article-title":"Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators","volume":"44","author":"Fujimoto","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8916","DOI":"10.1128\/JVI.00340-13","article-title":"Landscape of DNA Virus Associations across Human Malignant Cancers: Analysis of 3775 Cases Using RNA-Seq","volume":"87","author":"Khoury","year":"2013","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.ygeno.2013.07.002","article-title":"HIVID: An efficient method to detect HBV integration using low coverage sequencing","volume":"102","author":"Li","year":"2013","journal-title":"Genomics"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00535-015-1126-4","article-title":"Comprehensive analyses of mutations and hepatitis B virus integration in hepatocellular carcinoma with clinicopathological features","volume":"51","author":"Asahina","year":"2016","journal-title":"J. Gastroenterol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1016\/j.jhep.2016.02.005","article-title":"Novel pre-mRNA splicing of intronically integrated HBV generates oncogenic chimera in hepatocellular carcinoma","volume":"64","author":"Chiu","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/ng.3547","article-title":"Whole-genome mutational landscape and characterization of noncoding and structural mutations in liver cancer","volume":"48","author":"Fujimoto","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Gao, Q., Wang, Z.C., Duan, M., Lin, Y.H., Zhou, X.Y., Worthley, D.L., Wang, X.Y., Niu, G., Xia, Y., and Deng, M. (2017). Cell Culture System for Analysis of Genetic Heterogeneity Within Hepatocellular Carcinomas and Response to Pharmacologic Agents, Elsevier.","DOI":"10.1053\/j.gastro.2016.09.008"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.cell.2017.05.046","article-title":"Comprehensive and Integrative Genomic Characterization of Hepatocellular Carcinoma","volume":"169","author":"Ally","year":"2017","journal-title":"Cell"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Yoo, S., Wang, W., Wang, Q., Fiel, M.I., Lee, E., Hiotis, S.P., and Zhu, J. (2017). A pilot systematic genomic comparison of recurrence risks of hepatitis B virus-associated hepatocellular carcinoma with low- and high-degree liver fibrosis. BMC Med., 15.","DOI":"10.1186\/s12916-017-0973-7"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"25075","DOI":"10.18632\/oncotarget.25308","article-title":"Characterization of HBV integration patterns and timing in liver cancer and HBV-infected livers","volume":"9","author":"Furuta","year":"2018","journal-title":"Oncotarget"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/hep.30201","article-title":"Androgen Receptor Enhances Hepatic Telomerase Reverse Transcriptase Gene Transcription After Hepatitis B Virus Integration or Point Mutation in Promoter Region","volume":"69","author":"Li","year":"2019","journal-title":"Hepatology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3225","DOI":"10.7150\/jca.26052","article-title":"Molecular characterization of HBV DNA integration in patients with hepatitis and hepatocellular carcinoma","volume":"9","author":"Yang","year":"2018","journal-title":"J. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1038\/ncomms3513","article-title":"The landscape of viral expression and host gene fusion and adaptation in human cancer","volume":"4","author":"Tang","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Dong, H., Zhang, L., Qian, Z., Zhu, X., Zhu, G., Chen, Y., Xie, X., Ye, Q., Zang, J., and Ren, Z. (2015). Identification of HBV-MLL4 integration and its molecular basis in Chinese hepatocellular carcinoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123175"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2217\/epi.15.23","article-title":"DNA methylation consistency implicates the primary tumor cell origin of recurrent hepatocellular carcinoma","volume":"7","author":"Zhang","year":"2015","journal-title":"Epigenomics"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"28294","DOI":"10.1038\/srep28294","article-title":"Divergent viral presentation among human tumors and adjacent normal tissues","volume":"6","author":"Cao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Bayard, Q., Meunier, L., Peneau, C., Renault, V., Shinde, J., Nault, J.C., Mami, I., Couchy, G., Amaddeo, G., and Tubacher, E. (2018). Cyclin A2\/E1 activation defines a hepatocellular carcinoma subclass with a rearrangement signature of replication stress. Nat. Commun., 9.","DOI":"10.1038\/s41467-018-07552-9"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nrm3629","article-title":"Control of cell cycle transcription during G1 and S phases","volume":"14","author":"Bertoli","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/ng.2391","article-title":"Exome sequencing of hepatitis B virus-associated hepatocellular carcinoma","volume":"44","author":"Huang","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/carcin\/bgs406","article-title":"Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations","volume":"34","author":"Toh","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/0092-8674(94)90543-6","article-title":"Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age","volume":"79","author":"Hunter","year":"1994","journal-title":"Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/ncomms7120","article-title":"Whole-genome mutational landscape of liver cancers displaying biliary phenotype reveals hepatitis impact and molecular diversity","volume":"6","author":"Fujimoto","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Furler, R.L., and Uittenbogaart, C.H. (2012). GLI2 regulates TGF-\u03b21 in human CD4+ T cells: Implications in cancer and HIV pathogenesis. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040874"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.ccr.2012.04.012","article-title":"Distinct neural stem cell populations give rise to disparate brain tumors in response to N-MYC","volume":"21","author":"Swartling","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"8667","DOI":"10.1158\/0008-5472.CAN-08-2614","article-title":"Neuropilin-1 upholds dedifferentiation and propagation phenotypes of renal cell carcinoma cells by activating Akt and sonic hedgehog axes","volume":"68","author":"Cao","year":"2008","journal-title":"Cancer Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.1158\/0008-5472.CAN-06-3040","article-title":"Selective down-regulation of glioma-associated oncogene 2 inhibits the proliferation of hepatocellular carcinoma cells","volume":"67","author":"Kim","year":"2007","journal-title":"Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/hep.26394","article-title":"Hedgehog signaling pathway regulates autophagy in human hepatocellular carcinoma cells","volume":"58","author":"Wang","year":"2013","journal-title":"Hepatology"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1477-7819-11-25","article-title":"Expression of glioma-associated oncogene 2 (Gli 2) is correlated with poor prognosis in patients with hepatocellular carcinoma undergoing hepatectomy","volume":"11","author":"Zhang","year":"2013","journal-title":"World J. Surg. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.18632\/oncotarget.1555","article-title":"KMT2D maintains neoplastic cell proliferation and global histone H3 lysine 4 monomethylation","volume":"4","author":"Guo","year":"2013","journal-title":"Oncotarget"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Otsubo, T., Akiyama, Y., Hashimoto, Y., Shimada, S., Goto, K., and Yuasa, Y. (2011). Microrna-126 inhibits sox2 expression and contributes to gastric carcinogenesis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016617"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s12032-014-0461-2","article-title":"SOX5 promotes epithelial\u2013mesenchymal transition and cell invasion via regulation of Twist1 in hepatocellular carcinoma","volume":"32","author":"Wang","year":"2015","journal-title":"Med. Oncol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.2147\/OTT.S197087","article-title":"SOX5 promotes cell invasion and metastasis via activation of twist-mediated epithelial\u2013 mesenchymal transition in gastric cancer","volume":"12","author":"You","year":"2019","journal-title":"OncoTargets Ther."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Shiraishi, Y., Fujimoto, A., Furuta, M., Tanaka, H., Chiba, K.I., Boroevich, K.A., Abe, T., Kawakami, Y., Ueno, M., and Gotoh, K. (2014). Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114263"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"4641","DOI":"10.1016\/S0021-9258(18)32672-3","article-title":"Plasma fibronectin is synthesized and secreted by hepatocytes","volume":"258","author":"Tamkun","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/gcc.20020","article-title":"Parkin Gene Alterations in Hepatocellular Carcinoma","volume":"40","author":"Wang","year":"2004","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/BF00273649","article-title":"Population cytogenetics of folate-sensitive fragile sites\u2014I. Common fragile sites","volume":"80","year":"1988","journal-title":"Hum. Genet."},{"key":"ref_150","first-page":"1.30.1","article-title":"The GeneCards suite: From gene data mining to disease genome sequence analyses","volume":"2016","author":"Stelzer","year":"2016","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"7091","DOI":"10.1093\/emboj\/16.23.7091","article-title":"Cloning of an inr- and E-box-binding protein, TFII-I, that interacts physically and functionally with USF1","volume":"16","author":"Roy","year":"1997","journal-title":"EMBO J."},{"key":"ref_152","first-page":"5459","article-title":"GTF2I mutations are common in thymic epithelial tumors but not in hematological malignancies","volume":"37","author":"Tarrini","year":"2017","journal-title":"Anticancer Res."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"18","DOI":"10.21037\/med.2017.11.03","article-title":"GTF2I gene mutation\u2014A driver of thymoma pathogenesis","volume":"1","year":"2017","journal-title":"Mediastinum"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/ng.3016","article-title":"A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors","volume":"46","author":"Petrini","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Higuchi, R., Goto, T., Hirotsu, Y., Yokoyama, Y., Nakagomi, T., Otake, S., Amemiya, K., Oyama, T., Mochizuki, H., and Omata, M. (2020). Primary Driver Mutations in GTF2I Specific to the Development of Thymomas. Cancers, 12.","DOI":"10.3390\/cancers12082032"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"3721","DOI":"10.1073\/pnas.89.9.3721","article-title":"Molecular cloning and expression of human myocardial cGMP-inhibited cAMP phosphodiesterase","volume":"89","author":"Meacci","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1158\/1535-7163.MCT-18-1233","article-title":"Phosphodiesterase 3A Represents a Therapeutic Target that Drives Stem Cell-like Property and Metastasis in Breast Cancer","volume":"19","author":"Hao","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1038\/nchembio.1984","article-title":"Identification of cancer-cytotoxic modulators of PDE3A by predictive chemogenomics","volume":"12","author":"Lewis","year":"2016","journal-title":"Nat. Chem. Biol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.yexmp.2018.02.001","article-title":"Expression of proteins upregulated in hepatocellular carcinoma in patients with alcoholic hepatitis (AH) compared to non-alcoholic steatohepatitis (NASH): An immunohistochemical analysis of candidate proteins","volume":"104","author":"Lu","year":"2018","journal-title":"Exp. Mol. Pathol."},{"key":"ref_160","first-page":"902","article-title":"CHRM3 is a novel prognostic factor of poor prognosis in patients with endometrial carcinoma","volume":"7","author":"Wang","year":"2015","journal-title":"Am. J. Transl. Res."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"184","DOI":"10.2174\/1874467211666180119115828","article-title":"Targeting M3 Muscarinic Receptors for Colon Cancer Therapy","volume":"11","author":"Felton","year":"2018","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1152\/ajpgi.90519.2008","article-title":"Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells","volume":"296","author":"Xie","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Chen, J., Shin, V.Y., Cheuk, I., Siu, J., and Kwong, A. (2020). Abstract P1-07-01: Cholinergic receptor muscarinic 3 (CHRM3) contributes to breast cancer tumorigenesis through angiogenesis regulation. Cancer Res., 80.","DOI":"10.1158\/1538-7445.SABCS19-P1-07-01"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"608","DOI":"10.4103\/aja.aja_55_18","article-title":"Muscarinic acetylcholine receptor M1 mediates prostate cancer cell migration and invasion through hedgehog signaling","volume":"20","author":"Yin","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1007\/s13277-013-0982-x","article-title":"High expression of M3 muscarinic acetylcholine receptor is a novel biomarker of poor prognostic in patients with non-small cell lung cancer","volume":"34","author":"Wu","year":"2013","journal-title":"Tumor Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s005350050238","article-title":"Functional muscarinic m3 receptor expressed in gastric cancer cells stimulates tyrosine phosphorylation and MAP kinase","volume":"34","author":"Kodaira","year":"1999","journal-title":"J. Gastroenterol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Celiktas, M., Tanaka, I., Tripathi, S.C., Fahrmann, J.F., Aguilar-Bonavides, C., Villalobos, P., Delgado, O., Dhillon, D., Dennison, J.B., and Ostrin, E.J. (2017). Role of CPS1 in cell growth, metabolism, and prognosis in LKB1-inactivated lung adenocarcinoma. J. Natl. Cancer Inst., 109.","DOI":"10.1093\/jnci\/djw231"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/sj.embor.7400596","article-title":"Identification of preferred protein interactions by phage-display of the human Src homology-3 proteome","volume":"7","author":"Hiipakka","year":"2006","journal-title":"EMBO Rep."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"16527","DOI":"10.18632\/oncotarget.4113","article-title":"A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/ajmg.b.32530","article-title":"Genome-wide association study of HIV-associated neurocognitive disorder (HAND): A CHARTER group study","volume":"174","author":"Jia","year":"2017","journal-title":"Am. J. Med. Genet. Part B Neuropsychiatr. Genet. Off. Publ. Int. Soc. Psychiatr. Genet."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1001\/jamaneurol.2015.1424","article-title":"Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in PSEN1 with Familial Alzheimer Disease Among Caribbean Hispanics","volume":"72","author":"Lee","year":"2015","journal-title":"JAMA Neurol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1038\/s41467-020-16051-9","article-title":"SH3RF3 promotes breast cancer stem-like properties via JNK activation and PTX3 upregulation","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Mao, X., Bruneau, N., Gao, Q., Becq, H., Jia, Z., Xi, H., Shu, L., Wang, H., Szepetowski, P., and Aniksztejn, L. (2020). The Epilepsy of Infancy with Migrating Focal Seizures: Identification of de novo Mutations of the KCNT2 Gene That Exert Inhibitory Effects on the Corresponding Heteromeric KNa1.1\/KNa1.2 Potassium Channel. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00001"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1016\/j.ajpath.2011.08.014","article-title":"Insulin resistance and metabolic hepatocarcinogenesis with parent-of-origin effects in A\u00d7B mice","volume":"179","author":"Hines","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1053\/j.gastro.2016.11.042","article-title":"Molecular Classification of Hepatocellular Adenoma Associates with Risk Factors, Bleeding, and Malignant Transformation","volume":"152","author":"Nault","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"B\u00e9rub\u00e9, J.C., Gaudreault, N., Lavoie-Charland, E., Sbarra, L., Henry, C., Madore, A.M., Par\u00e9, P.D., Van Den Berge, M., Nickle, D., and Laviolette, M. (2016). Identification of Susceptibility Genes of Adult Asthma in French Canadian Women. Can. Respir. J., 2016.","DOI":"10.1155\/2016\/3564341"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1165\/rcmb.2014-0198OC","article-title":"Genome-wide association study identification of novel loci associated with airway responsiveness in chronic obstructive pulmonary disease","volume":"53","author":"Hansel","year":"2015","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ng.764","article-title":"Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47","volume":"43","author":"Anderson","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1093\/carcin\/bgu203","article-title":"Genetic polymorphisms in the 9p21 region associated with risk of multiple cancers","volume":"35","author":"Li","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Jo, J.H., Park, S.B., Park, S., Lee, H.S., Kim, C., Jung, D.E., and Song, S.Y. (2019). Novel gastric cancer stem cell-related marker LINGO2 is associated with cancer cell phenotype and patient outcome. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030555"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.1038\/s41467-019-12315-1","article-title":"TFF3 interacts with LINGO2 to regulate EGFR activation for protection against colitis and gastrointestinal helminths","volume":"10","author":"Belle","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4482","DOI":"10.1038\/onc.2014.378","article-title":"Tumor hypoxia induces nuclear paraspeckle formation through HIF-2\u03b1 dependent transcriptional activation of NEAT1 leading to cancer cell survival","volume":"34","author":"Choudhry","year":"2015","journal-title":"Oncogene"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1038\/ncomms6383","article-title":"The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer","volume":"5","author":"Chakravarty","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"4304","DOI":"10.1073\/pnas.1423819112","article-title":"SWI\/SNF chromatin-remodeling complexes function in noncoding RNA-dependent assembly of nuclear bodies","volume":"112","author":"Kawaguchi","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.micro.112408.134243","article-title":"Viruses, microRNAs, and host interactions","volume":"64","author":"Skalsky","year":"2010","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"18484","DOI":"10.1074\/jbc.M113.458158","article-title":"Hepatitis B viral RNA directly mediates down-regulation of the tumor suppressor microRNA miR-15a\/miR-16-1 in hepatocytes","volume":"288","author":"Wang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"3088","DOI":"10.1093\/bioinformatics\/btx346","article-title":"karyoploteR: An R\/Bioconductor package to plot customizable genomes displaying arbitrary data","volume":"33","author":"Gel","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ccr.2012.07.023","article-title":"TGF-\u03b2-miR-34a-CCL22 Signaling-Induced Treg Cell Recruitment Promotes Venous Metastases of HBV-Positive Hepatocellular Carcinoma","volume":"22","author":"Yang","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1365-2893.2010.01269.x","article-title":"Regulatory T cells in chronic hepatitis B patients affect the immunopathogenesis of hepatocellular carcinoma by suppressing the anti-tumour immune responses","volume":"17","author":"Zhang","year":"2010","journal-title":"J. Viral Hepat."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1365-2893.2008.00972.x","article-title":"Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C","volume":"15","author":"Fujita","year":"2008","journal-title":"J. Viral Hepat."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.3748\/wjg.v16.i48.6035","article-title":"Oxidative stress and antioxidants in hepatic pathogenesis","volume":"16","author":"Ha","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.canlet.2010.11.014","article-title":"Hepatitis B and C virus hepatocarcinogenesis: Lessons learned and future challenges","volume":"305","author":"Bouchard","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.4049\/jimmunol.170.3.1183","article-title":"Tumor Eradication by Hepatitis B Virus X Antigen-Specific CD8 + T Cells in Xenografted Nude Mice","volume":"170","author":"Chun","year":"2003","journal-title":"J. Immunol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1002\/hep.21594","article-title":"Impact of hepatitis B virus basic core promoter mutations on T cell response to an immunodominant HBx-derived epitope","volume":"45","author":"Malmassari","year":"2007","journal-title":"Hepatology"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1128\/JCM.41.12.5598-5603.2003","article-title":"Detection of the Hepatitis B Virus X Protein (HBx) Antigen and Anti-HBx Antibodies in Cases of Human Hepatocellular Carcinoma","volume":"41","author":"Hwang","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1002\/hep.22265","article-title":"The hepatitis B virus X protein induces paracrine activation of human hepatic stellate cells","volume":"47","author":"Majano","year":"2008","journal-title":"Hepatology"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1172\/JCI31457","article-title":"Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma","volume":"117","author":"Calvisi","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/hep.23247","article-title":"Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region-containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma","volume":"51","author":"Zhao","year":"2010","journal-title":"Hepatology"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.3748\/wjg.v17.i28.3353","article-title":"Hepatitis B virus and hepatocellular carcinoma at the miRNA level","volume":"17","author":"Zhang","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.cellsig.2013.01.019","article-title":"Epigenetic repression of miR-132 expression by the hepatitis B virus x protein in hepatitis B virus-related hepatocellular carcinoma","volume":"25","author":"Wei","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev.iy.13.040195.000333","article-title":"Hepatitis B virus immunopathogenesis","volume":"13","author":"Chisari","year":"1995","journal-title":"Annu. Rev. Immunol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.coi.2015.06.016","article-title":"Host\u2013virus interactions in hepatitis B virus infection","volume":"36","author":"Guidotti","year":"2015","journal-title":"Curr. Opin. Immunol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1016\/j.jhep.2016.01.026","article-title":"Adaptive immunity in HBV infection","volume":"64","author":"Bertoletti","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1128\/JVI.80.6.2797-2807.2006","article-title":"Immune suppression uncovers endogenous cytopathic effects of the hepatitis B virus","volume":"80","author":"Meuleman","year":"2006","journal-title":"J. Virol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1002\/jmv.24270","article-title":"Rethinking the pathogenesis of hepatitis B virus (HBV) infection","volume":"87","author":"Zhang","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1089\/vim.2019.0198","article-title":"Increased Proinflammatory Cytokine Production by Chronic Hepatitis B Patients with Mutant Hepatitis B Virus: Plausible Mechanisms Underlying Severe Liver Diseases in These Patients","volume":"33","author":"Raihan","year":"2020","journal-title":"Viral Immunol."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1053\/gast.2003.50053","article-title":"Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers","volume":"124","author":"Kao","year":"2003","journal-title":"Gastroenterology"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1093\/jnci\/djp180","article-title":"Associations between hepatitis B virus mutations and the risk of hepatocellular carcinoma: A meta-analysis","volume":"101","author":"Liu","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.12998\/wjcc.v9.i19.4890","article-title":"Molecular pathways in viral hepatitis-associated liver carcinogenesis: An update","volume":"9","author":"Elpek","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0065-230X(08)61037-4","article-title":"The pathogenesis of oncogenic avian retroviruses","volume":"39","author":"Enrietto","year":"1983","journal-title":"Adv. Cancer Res."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1006\/viro.1999.9678","article-title":"Activation of the N-myc2 oncogene by woodchuck hepatitis virus integration in the linked downstream b3n locus in woodchuck hepatocellular carcinoma","volume":"257","author":"Bruni","year":"1999","journal-title":"Virology"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1002\/hep.20106","article-title":"Integration of Woodchuck Hepatitis and N-myc Rearrangement Determine Size and Histologic Grade of Hepatic Tumors","volume":"39","author":"Jacob","year":"2004","journal-title":"Hepatology"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/modpathol.3800115","article-title":"Centrosome aberration accompanied with p53 mutation can induce genetic instability in hepatocellular carcinoma","volume":"17","author":"Nakajima","year":"2004","journal-title":"Mod. Pathol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1309\/BMTT-JBPD-D13H-1UVD","article-title":"Cytogenetic aberrations in primary and recurrent fibrolamellar hepatocellular carcinoma detected by comparative genomic hybridization","volume":"114","author":"Wilkens","year":"2000","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_215","doi-asserted-by":"crossref","unstructured":"Wooddell, C.I., Yuen, M.F., Chan, H.L.Y., Gish, R.G., Locarnini, S.A., Chavez, D., Ferrari, C., Given, B.D., Hamilton, J., and Kanner, S.B. (2017). RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg. Sci. Transl. Med., 9.","DOI":"10.1126\/scitranslmed.aan0241"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"2239","DOI":"10.31557\/APJCP.2019.20.8.2239","article-title":"Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis","volume":"20","author":"Poovorawan","year":"2019","journal-title":"Asian Pac. J. Cancer Prev. APJCP"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1128\/JVI.02844-06","article-title":"Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection","volume":"81","author":"Boni","year":"2007","journal-title":"J. Virol."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1136\/postgradmedj-2011-301073rep","article-title":"Innate and adaptive immune responses in chronic hepatitis B virus infections: Towards restoration of immune control of viral infection","volume":"89","author":"Bertoletti","year":"2013","journal-title":"Postgrad. Med. J."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S1535-6108(02)00024-7","article-title":"A matter of life and death","volume":"1","author":"Green","year":"2002","journal-title":"Cancer Cell"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/s41575-020-0332-6","article-title":"Progress towards elimination goals for viral hepatitis","volume":"17","author":"Cox","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1002\/hep.31030","article-title":"Guidance for Design and Endpoints of Clinical Trials in Chronic Hepatitis B\u2014Report From the 2019 EASL-AASLD HBV Treatment Endpoints Conference","volume":"71","author":"Cornberg","year":"2020","journal-title":"Hepatology"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.jfma.2015.06.003","article-title":"Perspectives and control of hepatitis B virus infection in Taiwan","volume":"114","author":"Lin","year":"2015","journal-title":"J. Formos. Med. Assoc. Taiwan Yi Zhi"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.jfma.2018.08.020","article-title":"Hepatitis B: From control to cure","volume":"117","author":"Kao","year":"2018","journal-title":"J. Formos. Med. Assoc."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/8\/1787\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:49:37Z","timestamp":1760165377000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/8\/1787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,23]]},"references-count":223,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["microorganisms9081787"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9081787","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,23]]}}}