{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:31:42Z","timestamp":1792150302925,"version":"4.4.0"},"reference-count":140,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and a leading cause of cancer-related deaths worldwide. Although much progress has been made in HCC drug development in recent years, treatment options remain limited. The major cause of HCC is chronic hepatitis B virus (HBV) infection. Despite the existence of a vaccine, more than 250 million individuals are chronically infected by HBV. Current antiviral therapies can repress viral replication but to date there is no cure for chronic hepatitis B. Of note, inhibition of viral replication reduces but does not eliminate the risk of HCC development. HBV contributes to liver carcinogenesis by direct and indirect effects. This review summarizes the current knowledge of HBV-induced host epigenetic alterations and their association with HCC, with an emphasis on the interactions between HBV proteins and the host cell epigenetic machinery leading to modulation of gene expression.<\/jats:p>","DOI":"10.3390\/jcm10081715","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T10:20:11Z","timestamp":1618568411000},"page":"1715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Host Epigenetic Alterations and Hepatitis B Virus-Associated Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1606-0131","authenticated-orcid":false,"given":"Mirjam B.","family":"Zeisel","sequence":"first","affiliation":[{"name":"Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Universit\u00e9 de Lyon 1 (UCBL1), 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2021-4394","authenticated-orcid":false,"given":"Francesca","family":"Guerrieri","sequence":"additional","affiliation":[{"name":"Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Universit\u00e9 de Lyon 1 (UCBL1), 69003 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4978-0875","authenticated-orcid":false,"given":"Massimo","family":"Levrero","sequence":"additional","affiliation":[{"name":"Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Universit\u00e9 de Lyon 1 (UCBL1), 69003 Lyon, France"},{"name":"Hospices Civils de Lyon, H\u00f4pital Croix Rousse, Service d\u2019H\u00e9pato-Gastroent\u00e9rologie, 69004 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,16]]},"reference":[{"key":"ref_1","unstructured":"Observatory, I.-W.G.C. (2020, August 17). Globocan 2020 Database. Available online: https:\/\/gco.iarc.fr\/."},{"key":"ref_2","unstructured":"European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J. Hepatol., 69, 182\u2013236."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.1016\/j.jhep.2016.02.021","article-title":"Mechanisms of HBV-induced hepatocellular carcinoma","volume":"64","author":"Levrero","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Caruso, S., O\u2019Brien, D.R., Cleary, S.P., Roberts, L.R., and Zucman-Rossi, J. (2020). Genetics of HCC: Novel approaches to explore molecular diversity. Hepatology.","DOI":"10.1002\/hep.31394"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.jhep.2019.06.001","article-title":"Molecular and histological correlations in liver cancer","volume":"71","author":"Calderaro","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/s41467-019-14050-z","article-title":"Intratumoral heterogeneity and clonal evolution in liver cancer","volume":"11","author":"Losic","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S211","DOI":"10.37765\/ajmc.2020.88512","article-title":"A concise review of the changing landscape of hepatocellular carcinoma","volume":"26","author":"Draper","year":"2020","journal-title":"Am. J. Manag. Care"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.jhep.2019.09.010","article-title":"Molecular therapies for HCC: Looking outside the box","volume":"72","author":"Faivre","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1056\/NEJMoa1915745","article-title":"Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pinter, M., Jain, R.K., and Duda, D.G. (2020). The Current Landscape of Immune Checkpoint Blockade in Hepatocellular Carcinoma: A Review. JAMA Oncol.","DOI":"10.1001\/jamaoncol.2020.3381"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1136\/gutjnl-2020-321702","article-title":"Immunotherapy for advanced hepatocellular carcinoma: A focus on special subgroups","volume":"70","author":"Pinter","year":"2021","journal-title":"Gut"},{"key":"ref_12","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_13","doi-asserted-by":"crossref","unstructured":"Peneau, C., Imbeaud, S., La Bella, T., Hirsch, T.Z., Caruso, S., Calderaro, J., Paradis, V., Blanc, J.F., Letouze, E., and Nault, J.C. (2021). Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma. Gut.","DOI":"10.1136\/gutjnl-2020-323153"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1053\/j.gastro.2006.01.001","article-title":"Hepatitis B virus replication is regulated by the acetylation status of hepatitis B virus cccDNA-bound H3 and H4 histones","volume":"130","author":"Pollicino","year":"2006","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19975","DOI":"10.1073\/pnas.0908365106","article-title":"Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function","volume":"106","author":"Belloni","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1055\/s-0033-1345721","article-title":"Molecular mechanisms of HBV-associated hepatocarcinogenesis","volume":"33","author":"Guerrieri","year":"2013","journal-title":"Semin. Liver Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1016\/j.jhep.2015.06.023","article-title":"HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase","volume":"63","author":"Riviere","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"E5715","DOI":"10.1073\/pnas.1518090112","article-title":"Mapping of histone modifications in episomal HBV cccDNA uncovers an unusual chromatin organization amenable to epigenetic manipulation","volume":"112","author":"Tropberger","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2066","DOI":"10.1002\/hep.29479","article-title":"Epigenetic regulation of hepatitis B virus covalently closed circular DNA: Implications for epigenetic therapy against chronic hepatitis B","volume":"66","author":"Hong","year":"2017","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1038\/s41467-018-03999-y","article-title":"Epigenetic landscape influences the liver cancer genome architecture","volume":"9","author":"Hama","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Guerrieri, F., Belloni, L., D\u2019Andrea, D., Pediconi, N., Le Pera, L., Testoni, B., Scisciani, C., Floriot, O., Zoulim, F., and Tramontano, A. (2017). Genome-wide identification of direct HBx genomic targets. BMC Genom., 18.","DOI":"10.1186\/s12864-017-3561-5"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/ng.3252","article-title":"Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets","volume":"47","author":"Schulze","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jhep.2019.03.007","article-title":"A comprehensive study of epigenetic alterations in hepatocellular carcinoma identifies potential therapeutic targets","volume":"71","author":"Bayo","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e12791","DOI":"10.1111\/cpr.12791","article-title":"The roles of mutated SWI\/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review","volume":"53","author":"Hu","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Manna, D., and Sarkar, D. (2020). Non-Coding RNAs: Regulating Disease Progression and Therapy Resistance in Hepatocellular Carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12051243"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40169-019-0230-0","article-title":"Epigenetics of hepatocellular carcinoma","volume":"8","author":"Toh","year":"2019","journal-title":"Clin. Transl. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Barrena, M.G., Arechederra, M., Colyn, L., Berasain, C., and Avila, M.A. (2020). Epigenetics in hepatocellular carcinoma development and therapy: The tip of a big iceberg. JHEP Rep., 100167.","DOI":"10.1016\/j.jhepr.2020.100167"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.antiviral.2017.11.015","article-title":"The diverse functions of the hepatitis B core\/capsid protein (HBc) in the viral life cycle: Implications for the development of HBc-targeting antivirals","volume":"149","author":"Diab","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.1099\/vir.0.18966-0","article-title":"Hepatitis B virus downregulates the human interferon-inducible MxA promoter through direct interaction of precore\/core proteins","volume":"84","author":"Fernandez","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/cdd.2008.144","article-title":"Hepatitis B virus core protein inhibits TRAIL-induced apoptosis of hepatocytes by blocking DR5 expression","volume":"16","author":"Du","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.antiviral.2015.04.013","article-title":"The hepatitis B virus (HBV) core protein enhances the transcription activation of CRE via the CRE\/CREB\/CBP pathway","volume":"120","author":"Xiang","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Salerno, D., Chiodo, L., Alfano, V., Floriot, O., Cottone, G., Paturel, A., Pallocca, M., Plissonnier, M.L., Jeddari, S., and Belloni, L. (2020). Hepatitis B protein HBx binds the DLEU2 lncRNA to sustain cccDNA and host cancer-related gene transcription. Gut.","DOI":"10.1136\/gutjnl-2019-319637"},{"key":"ref_34","first-page":"276A","article-title":"The nuclear function of Hepatitis B capsid (HBc) protein is to inhibit IFN response very early after infection of hepatocytes","volume":"58","author":"Gruffaz","year":"2013","journal-title":"Hepatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S155","DOI":"10.1016\/S0168-8278(13)60380-3","article-title":"Hepatitis B core (HBc) protein is a key and very early negative regulator of the interferon response","volume":"58","author":"Gruffaz","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_36","first-page":"277A","article-title":"HAPs hepatitis B virus (HBV) capsid inhibitors block core protein interaction with the viral minichromosome and host cell genes and affect cccDNA transcription","volume":"58","author":"Belloni","year":"2013","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Guo, Y., Kang, W., Lei, X., Li, Y., Xiang, A., Liu, Y., Zhao, J., Zhang, J., and Yan, Z. (2012). Hepatitis B viral core protein disrupts human host gene expression by binding to promoter regions. BMC Genom., 13.","DOI":"10.1186\/1471-2164-13-563"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1002\/hep.27732","article-title":"DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma","volume":"61","author":"Villanueva","year":"2015","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Hernandez-Vargas, H., Lambert, M.P., Le Calvez-Kelm, F., Gouysse, G., McKay-Chopin, S., Tavtigian, S.V., Scoazec, J.Y., and Herceg, Z. (2010). Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009749"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.jhep.2010.07.027","article-title":"Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake","volume":"54","author":"Lambert","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sun, S., Li, Y., Han, S., Jia, H., Li, X., and Li, X. (2019). A comprehensive genome-wide profiling comparison between HBV and HCV infected hepatocellular carcinoma. BMC Med. Genom., 12.","DOI":"10.1186\/s12920-019-0580-x"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Kuss-Duerkop, S.K., Westrich, J.A., and Pyeon, D. (2018). DNA Tumor Virus Regulation of Host DNA Methylation and Its Implications for Immune Evasion and Oncogenesis. Viruses, 10.","DOI":"10.3390\/v10020082"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1053\/j.gastro.2007.01.034","article-title":"Aberrant epigenetic modifications in hepatocarcinogenesis induced by hepatitis B virus X protein","volume":"132","author":"Park","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9555","DOI":"10.1073\/pnas.1400604111","article-title":"HBx induces hypomethylation of distal intragenic CpG islands required for active expression of developmental regulators","volume":"111","author":"Lee","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1053\/j.gastro.2013.10.056","article-title":"Hepatitis virus infection affects DNA methylation in mice with humanized livers","volume":"146","author":"Okamoto","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13148-015-0053-9","article-title":"Aberrant DNA methylation of imprinted loci in hepatocellular carcinoma and after in vitro exposure to common risk factors","volume":"7","author":"Lambert","year":"2015","journal-title":"Clin. Epigenetics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"44877","DOI":"10.18632\/oncotarget.6270","article-title":"Genomic responses to hepatitis B virus (HBV) infection in primary human hepatocytes","volume":"6","author":"Ancey","year":"2015","journal-title":"Oncotarget"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1002\/hep.30146","article-title":"Global DNA 5-Hydroxymethylcytosine and 5-Formylcytosine Contents Are Decreased in the Early Stage of Hepatocellular Carcinoma","volume":"69","author":"Liu","year":"2019","journal-title":"Hepatology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6617","DOI":"10.1038\/sj.onc.1208827","article-title":"Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1","volume":"24","author":"Lee","year":"2005","journal-title":"Oncogene"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.1158\/0008-5472.CAN-07-0529","article-title":"Expression of DNA methyltransferase 1 is activated by hepatitis B virus X protein via a regulatory circuit involving the p16INK4a-cyclin D1-CDK 4\/6-pRb-E2F1 pathway","volume":"67","author":"Jung","year":"2007","journal-title":"Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jhep.2008.10.019","article-title":"Epigenetic modification induced by hepatitis B virus X protein via interaction with de novo DNA methyltransferase DNMT3A","volume":"50","author":"Zheng","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_53","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_54","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1038\/oncsis.2012.26","article-title":"Epigenetic control of metastasis-associated protein 1 gene expression by hepatitis B virus X protein during hepatocarcinogenesis","volume":"1","author":"Lee","year":"2012","journal-title":"Oncogenesis"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/ijc.28697","article-title":"Epigenetic silencing of SFRP1 and SFRP5 by hepatitis B virus X protein enhances hepatoma cell tumorigenicity through Wnt signaling pathway","volume":"135","author":"Xie","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3892\/mmr.2015.4545","article-title":"Hepatitis B virus X protein upregulates DNA methyltransferase 3A\/3B and enhances SOCS-1CpG island methylation","volume":"13","author":"Fu","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/sj.onc.1209154","article-title":"Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation","volume":"25","author":"Ying","year":"2006","journal-title":"Oncogene"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3892\/or.2013.2848","article-title":"Upregulation of DNMT1 mediated by HBx suppresses RASSF1A expression independent of DNA methylation","volume":"31","author":"Qiu","year":"2014","journal-title":"Oncol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10238-012-0182-9","article-title":"Silencing of PCDH10 in hepatocellular carcinoma via de novo DNA methylation independent of HBV infection or HBX expression","volume":"13","author":"Fang","year":"2013","journal-title":"Clin. Exp. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/onc.2011.255","article-title":"Epigenetic repression of E-cadherin expression by hepatitis B virus x antigen in liver cancer","volume":"31","author":"Arzumanyan","year":"2012","journal-title":"Oncogene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1101\/gad.276568.115","article-title":"Role of TET enzymes in DNA methylation, development, and cancer","volume":"30","author":"Rasmussen","year":"2016","journal-title":"Genes Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1016\/j.jmb.2019.07.039","article-title":"Protein Interactions at Oxidized 5-Methylcytosine Bases","volume":"432","author":"Pfeifer","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1002\/hep.24606","article-title":"The histone deacetylase 4\/SP1\/microrna-200a regulatory network contributes to aberrant histone acetylation in hepatocellular carcinoma","volume":"54","author":"Yuan","year":"2011","journal-title":"Hepatology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Freese, K., Seitz, T., Dietrich, P., Lee, S.M.L., Thasler, W.E., Bosserhoff, A., and Hellerbrand, C. (2019). Histone Deacetylase Expressions in Hepatocellular Carcinoma and Functional Effects of Histone Deacetylase Inhibitors on Liver Cancer Cells In Vitro. Cancers, 11.","DOI":"10.3390\/cancers11101587"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.virusres.2008.09.006","article-title":"Hepatitis B virus-X protein recruits histone deacetylase 1 to repress insulin-like growth factor binding protein 3 transcription","volume":"139","author":"Shon","year":"2009","journal-title":"Virus Res."},{"key":"ref_66","first-page":"276","article-title":"Hepatitis B virus X (HBX) protein upregulates beta-catenin in a human hepatic cell line by sequestering SIRT1 deacetylase","volume":"28","author":"Srisuttee","year":"2012","journal-title":"Oncol. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"4277","DOI":"10.1074\/jbc.M606774200","article-title":"The hepatitis B virus X protein functionally interacts with CREB-binding protein\/p300 in the regulation of CREB-mediated transcription","volume":"282","author":"Cougot","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_68","first-page":"956","article-title":"Epigenetic modulation of insulin-like growth factor-II overexpression by hepatitis B virus X protein in hepatocellular carcinoma","volume":"5","author":"Liu","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1309\/AJCPTFDSE2V3LCZP","article-title":"Characteristics of hepatic igf-ii expression and monitored levels of circulating igf-ii mRNA in metastasis of hepatocellular carcinoma","volume":"134","author":"Qian","year":"2010","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.molcel.2012.11.006","article-title":"Histone lysine methylation dynamics: Establishment, regulation, and biological impact","volume":"48","author":"Black","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/labinvest.2008.52","article-title":"The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma","volume":"88","author":"Sasaki","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1136\/gut.2010.231993","article-title":"EZH2 protein: A promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies","volume":"60","author":"Cai","year":"2011","journal-title":"Gut"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s11684-013-0253-7","article-title":"Epigenetic dysregulation in hepatocellular carcinoma: Focus on polycomb group proteins","volume":"7","author":"Au","year":"2013","journal-title":"Front. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1002\/hep.26083","article-title":"Histone lysine methyltransferase, suppressor of variegation 3\u20139 homolog 1, promotes hepatocellular carcinoma progression and is negatively regulated by microRNA-125b","volume":"57","author":"Fan","year":"2013","journal-title":"Hepatology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/hep.28304","article-title":"Up-regulation of histone methyltransferase SETDB1 by multiple mechanisms in hepatocellular carcinoma promotes cancer metastasis","volume":"63","author":"Wong","year":"2016","journal-title":"Hepatology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jhep.2017.05.015","article-title":"Histone methyltransferase G9a promotes liver cancer development by epigenetic silencing of tumor suppressor gene RARRES3","volume":"67","author":"Wei","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"84883","DOI":"10.18632\/oncotarget.12751","article-title":"Hepatitis B virus X protein influences enrichment profiles of H3K9me3 on promoter regions in human hepatoma cell lines","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1093\/infdis\/jiaa317","article-title":"Signal activation of hepatitis B virus-related hepatocarcinogenesis by upregulation of SUV39h1","volume":"222","author":"Takeuchi","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1096\/fj.201700645RRRRR","article-title":"SUV39H1\/DNMT3A-dependent methylation of the RB1 promoter stimulates PIN1 expression and melanoma development","volume":"32","author":"Kim","year":"2018","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1158\/0008-5472.CAN-14-2928","article-title":"PLK1 and HOTAIR Accelerate Proteasomal Degradation of SUZ12 and ZNF198 during Hepatitis B Virus-Induced Liver Carcinogenesis","volume":"75","author":"Zhang","year":"2015","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/hep.28698","article-title":"RNA helicase DEAD box protein 5 regulates Polycomb repressive complex 2\/Hox transcript antisense intergenic RNA function in hepatitis B virus infection and hepatocarcinogenesis","volume":"64","author":"Zhang","year":"2016","journal-title":"Hepatology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1002\/hep.30947","article-title":"HBx Protein Contributes to Liver Carcinogenesis by H3K4me3 Modification Through Stabilizing WD Repeat Domain 5 Protein","volume":"71","author":"Gao","year":"2020","journal-title":"Hepatology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nsmb0709-678","article-title":"WDR5, a complexed protein","volume":"16","author":"Trievel","year":"2009","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s12032-008-9144-1","article-title":"Hepatitis B virus X protein upregulates expression of SMYD3 and C-MYC in HepG2 cells","volume":"26","author":"Yang","year":"2009","journal-title":"Med. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.molcel.2016.11.003","article-title":"Arginine Methylation: The Coming of Age","volume":"65","author":"Blanc","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/s41580-019-0155-x","article-title":"The regulation, functions and clinical relevance of arginine methylation","volume":"20","author":"Guccione","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"115444","DOI":"10.18632\/oncotarget.23296","article-title":"Novel prognostic marker PRMT1 regulates cell growth via downregulation of CDKN1A in HCC","volume":"8","author":"Ryu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1159\/000490983","article-title":"PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway","volume":"47","author":"Zhang","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"112152","DOI":"10.1016\/j.yexcr.2020.112152","article-title":"PRMT2 accelerates tumorigenesis of hepatocellular carcinoma by activating Bcl2 via histone H3R8 methylation","volume":"394","author":"Hu","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/s12967-015-0721-8","article-title":"Targeting protein arginine methyltransferase 5 inhibits human hepatocellular carcinoma growth via the downregulation of beta-catenin","volume":"13","author":"Zhang","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"381","DOI":"10.3892\/ijo.2017.3833","article-title":"The protein arginine methyltransferase 5 promotes malignant phenotype of hepatocellular carcinoma cells and is associated with adverse patient outcomes after curative hepatectomy","volume":"50","author":"Shimizu","year":"2017","journal-title":"Int. J. Oncol."},{"key":"ref_92","first-page":"536","article-title":"Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells","volume":"40","author":"Jeon","year":"2018","journal-title":"Oncol. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1038\/s41467-018-04006-0","article-title":"The LINC01138 drives malignancies via activating arginine methyltransferase 5 in hepatocellular carcinoma","volume":"9","author":"Li","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1111\/cas.13598","article-title":"PRMT9 promotes hepatocellular carcinoma invasion and metastasis via activating PI3K\/Akt\/GSK-3beta\/Snail signaling","volume":"109","author":"Jiang","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.celrep.2018.09.053","article-title":"PRMT6 Regulates RAS\/RAF Binding and MEK\/ERK-Mediated Cancer Stemness Activities in Hepatocellular Carcinoma through CRAF Methylation","volume":"25","author":"Chan","year":"2018","journal-title":"Cell Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/hep.30923","article-title":"CRAF Methylation by PRMT6 Regulates Aerobic Glycolysis-Driven Hepatocarcinogenesis via ERK-Dependent PKM2 Nuclear Relocalization and Activation","volume":"71","author":"Wong","year":"2020","journal-title":"Hepatology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/hep.29133","article-title":"PRMT5 restricts hepatitis B virus replication through epigenetic repression of covalently closed circular DNA transcription and interference with pregenomic RNA encapsidation","volume":"66","author":"Zhang","year":"2017","journal-title":"Hepatology"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"4360","DOI":"10.1128\/JVI.02574-12","article-title":"Methyltransferase PRMT1 is a binding partner of HBx and a negative regulator of hepatitis B virus transcription","volume":"87","author":"Benhenda","year":"2013","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1126\/science.1138341","article-title":"RNA maps reveal new RNA classes and a possible function for pervasive transcription","volume":"316","author":"Kapranov","year":"2007","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/hep.22749","article-title":"Differential microRNA expression between hepatitis B and hepatitis C leading disease progression to hepatocellular carcinoma","volume":"49","author":"Ura","year":"2009","journal-title":"Hepatology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/ijc.28075","article-title":"Identification of microRNAs specifically expressed in hepatitis C virus-associated hepatocellular carcinoma","volume":"133","author":"Diaz","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"7836","DOI":"10.3748\/wjg.v19.i44.7836","article-title":"Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma: Dysregulation and implications for early detection, diagnosis and therapy","volume":"19","author":"Hou","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.bbagrm.2011.07.010","article-title":"MicroRNA in HCV infection and liver cancer","volume":"1809","author":"Kumar","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s12275-014-4267-x","article-title":"The role of microRNAs in hepatitis C virus replication and related liver diseases","volume":"52","author":"Lee","year":"2014","journal-title":"J. Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/nrgastro.2017.169","article-title":"Non-coding RNAs in hepatocellular carcinoma: Molecular functions and pathological implications","volume":"15","author":"Wong","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhep.2014.10.004","article-title":"miR-122--a key factor and therapeutic target in liver disease","volume":"62","author":"Bandiera","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Plissonnier, M.L., Herzog, K., Levrero, M., and Zeisel, M.B. (2018). Non-Coding RNAs and Hepatitis C Virus-Induced Hepatocellular Carcinoma. Viruses, 10.","DOI":"10.3390\/v10110591"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.3389\/fonc.2020.01271","article-title":"Dysregulated microRNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Potential as Biomarkers and Therapeutic Targets","volume":"10","author":"Xu","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"545","DOI":"10.2741\/4734","article-title":"Role of microRNAs in the development of hepatocellular carcinoma and acquired drug resistance","volume":"24","author":"Tricoli","year":"2019","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7375","DOI":"10.3748\/wjg.v21.i24.7375","article-title":"Hepatitis B virus and microRNAs: Complex interactions affecting hepatitis B virus replication and hepatitis B virus-associated diseases","volume":"21","author":"Lamontagne","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1096\/fj.11-187781","article-title":"A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B virus and negatively regulates viral gene expression and replication","volume":"25","author":"Chen","year":"2011","journal-title":"FASEB J."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Damania, P., Sen, B., Dar, S.B., Kumar, S., Kumari, A., Gupta, E., Sarin, S.K., and Venugopal, S.K. (2014). Hepatitis B virus induces cell proliferation via HBx-induced microRNA-21 in hepatocellular carcinoma by targeting programmed cell death protein4 (PDCD4) and phosphatase and tensin homologue (PTEN). PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091745"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1053\/j.gastro.2007.05.022","article-title":"MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer","volume":"133","author":"Meng","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1016\/j.ejca.2014.07.008","article-title":"Hepatitis B virus X protein promotes hepatocellular carcinoma transformation through interleukin-6 activation of microRNA-21 expression","volume":"50","author":"Li","year":"2014","journal-title":"Eur. J. Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"23521","DOI":"10.1038\/srep23521","article-title":"HBx-upregulated lncRNA UCA1 promotes cell growth and tumorigenesis by recruiting EZH2 and repressing p27Kip1\/CDK2 signaling","volume":"6","author":"Hu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nrd.2016.256","article-title":"Marked for death: Targeting epigenetic changes in cancer","volume":"16","author":"Pfister","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13148-019-0776-0","article-title":"The timeline of epigenetic drug discovery: From reality to dreams","volume":"11","author":"Ganesan","year":"2019","journal-title":"Clin. Epigenet."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s12943-020-01197-3","article-title":"Epigenetic regulation in human cancer: The potential role of epi-drug in cancer therapy","volume":"19","author":"Lu","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41571-019-0267-4","article-title":"Combining epigenetic drugs with other therapies for solid tumours - past lessons and future promise","volume":"17","author":"Morel","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"110367","DOI":"10.18632\/oncotarget.22775","article-title":"Resminostat induces changes in epithelial plasticity of hepatocellular carcinoma cells and sensitizes them to sorafenib-induced apoptosis","volume":"8","author":"Soukupova","year":"2017","journal-title":"Oncotarget"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s00262-018-2283-0","article-title":"Enhanced anti-tumor efficacy of checkpoint inhibitors in combination with the histone deacetylase inhibitor Belinostat in a murine hepatocellular carcinoma model","volume":"68","author":"Llopiz","year":"2019","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"16698","DOI":"10.18632\/oncotarget.3677","article-title":"An open-label, single-arm, phase I\/II study of lower-dose decitabine based therapy in patients with advanced hepatocellular carcinoma","volume":"6","author":"Mei","year":"2015","journal-title":"Oncotarget"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1200\/JCO.2011.41.2395","article-title":"Epigenetic therapy using belinostat for patients with unresectable hepatocellular carcinoma: A multicenter phase I\/II study with biomarker and pharmacokinetic analysis of tumors from patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group","volume":"30","author":"Yeo","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jhep.2016.02.043","article-title":"Resminostat plus sorafenib as second-line therapy of advanced hepatocellular carcinoma\u2014The SHELTER study","volume":"65","author":"Bitzer","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1016\/j.febslet.2010.04.067","article-title":"Curcumin inhibits hepatitis B virus via down-regulation of the metabolic coactivator PGC-1alpha","volume":"584","author":"Rechtman","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1349-7006.1989.tb02308.x","article-title":"Demethylation by 5-azacytidine results in the expression of hepatitis B virus surface antigen in transgenic mice","volume":"80","author":"Araki","year":"1989","journal-title":"Jpn. J. Cancer Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ijc.2910520124","article-title":"Enhancement of hepatitis-B surface-antigen expression by 5-azacytidine in a hepatitis-B-virus-transfected cell line","volume":"52","author":"Miyoshi","year":"1992","journal-title":"Int. J. Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.3324\/haematol.2009.008607","article-title":"Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: A case series report","volume":"94","author":"Ritchie","year":"2009","journal-title":"Haematologica"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"5159","DOI":"10.3748\/wjg.v19.i31.5159","article-title":"Effects of SAHA on proliferation and apoptosis of hepatocellular carcinoma cells and hepatitis B virus replication","volume":"19","author":"Wang","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_130","first-page":"1087","article-title":"Silencing of GSTP1 gene by CpG island DNA hypermethylation in HBV-associated hepatocellular carcinomas","volume":"8","author":"Zhong","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1158\/1940-6207.CAPR-12-0001","article-title":"Resveratrol helps recovery from fatty liver and protects against hepatocellular carcinoma induced by hepatitis B virus X protein in a mouse model","volume":"5","author":"Lin","year":"2012","journal-title":"Cancer Prev. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"419","DOI":"10.4142\/jvs.2017.18.4.419","article-title":"Inhibitory effects of resveratrol on hepatitis B virus X protein-induced hepatocellular carcinoma","volume":"18","author":"Park","year":"2017","journal-title":"J. Vet. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.bbrc.2012.10.102","article-title":"SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis","volume":"429","author":"Srisuttee","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/carcin\/bgs365","article-title":"Histone deacetylase inhibitor suberoylanilide hydroxamic acid suppresses the pro-oncogenic effects induced by hepatitis B virus pre-S2 mutant oncoprotein and represents a potential chemopreventive agent in high-risk chronic HBV patients","volume":"34","author":"Hsieh","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.1038\/s41598-018-23318-1","article-title":"Delta-like 3 is silenced by HBx via histone acetylation in HBV-associated HCCs","volume":"8","author":"Hamamoto","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nrd4018","article-title":"Targeting long non-coding RNA to therapeutically upregulate gene expression","volume":"12","author":"Wahlestedt","year":"2013","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_137","first-page":"878","article-title":"HCV infection and miravirsen","volume":"369","author":"Janssen","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/S0140-6736(16)31715-9","article-title":"Safety, tolerability, and antiviral effect of RG-101 in patients with chronic hepatitis C: A phase 1B, double-blind, randomised controlled trial","volume":"389","author":"Stelma","year":"2017","journal-title":"Lancet"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00281-020-00780-6","article-title":"Epigenetic modulation in chronic hepatitis B virus infection","volume":"42","author":"Dandri","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"3550","DOI":"10.1111\/febs.14094","article-title":"Virus-host interplay in hepatitis B virus infection and epigenetic treatment strategies","volume":"284","author":"Hensel","year":"2017","journal-title":"FEBS J."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/8\/1715\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:48:37Z","timestamp":1760161717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/8\/1715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,16]]},"references-count":140,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["jcm10081715"],"URL":"https:\/\/doi.org\/10.3390\/jcm10081715","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,16]]}}}