{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:22:04Z","timestamp":1791836524162,"version":"4.3.4"},"reference-count":44,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T00:00:00Z","timestamp":1671580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jhep-reports.eu","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["JHEP Reports"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1016\/j.jhepr.2022.100664","type":"journal-article","created":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T19:53:40Z","timestamp":1672084420000},"page":"100664","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"title":["Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells"],"prefix":"10.1016","volume":"5","author":[{"given":"Abhishek","family":"Aggarwal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela M.","family":"Odorizzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Brodbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2746-4422","authenticated-orcid":false,"given":"Nicholas","family":"van Buuren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaryVic","family":"Adona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silpa","family":"Suthram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vithika","family":"Suri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Trowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Turner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Marcellin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Buti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuj","family":"Gaggar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon P.","family":"Fletcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Diehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5639-506X","authenticated-orcid":false,"given":"Becket","family":"Feierbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Balsitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jhepr.2022.100664_bib1","series-title":"Global hepatitis report","year":"2017"},{"key":"10.1016\/j.jhepr.2022.100664_bib2","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1136\/gutjnl-2013-305517","article-title":"HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: clinical outcomes and durability","volume":"63","author":"Kim","year":"2014","journal-title":"Gut"},{"issue":"Suppl. 1","key":"10.1016\/j.jhepr.2022.100664_bib3","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jhep.2016.01.027","article-title":"Overview of hepatitis B viral replication and genetic variability","volume":"64","author":"Tong","year":"2016","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100664_bib4","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3390\/v9040075","article-title":"HBV DNA integration: molecular mechanisms and clinical implications","volume":"9","author":"Tu","year":"2017","journal-title":"Viruses"},{"key":"10.1016\/j.jhepr.2022.100664_bib5","doi-asserted-by":"crossref","first-page":"368","DOI":"10.3390\/v13030368","article-title":"HBV-integration studies in the clinic: role in the natural history of infection","volume":"13","author":"Pollicino","year":"2021","journal-title":"Viruses"},{"key":"10.1016\/j.jhepr.2022.100664_bib6","article-title":"Targeted long-read sequencing reveals clonally expanded HBV-associated chromosomal translocations in patients with chronic hepatitis B","volume":"4","author":"van Buuren","year":"2022","journal-title":"JHEP Rep"},{"key":"10.1016\/j.jhepr.2022.100664_bib7","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":"10.1016\/j.jhepr.2022.100664_bib8","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":"10.1016\/j.jhepr.2022.100664_bib9","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/s41426-018-0145-7","article-title":"Sequence analysis of integrated hepatitis B virus DNA during HBeAg-seroconversion","volume":"7","author":"Budzinska","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"10.1016\/j.jhepr.2022.100664_bib10","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":"10.1016\/j.jhepr.2022.100664_bib11","article-title":"Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma","volume":"7","author":"Zhao","year":"2016","journal-title":"Nat Commun"},{"key":"10.1016\/j.jhepr.2022.100664_bib12","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1136\/gutjnl-2020-323153","article-title":"Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma","volume":"71","author":"P\u00e9neau","year":"2022","journal-title":"Gut"},{"key":"10.1016\/j.jhepr.2022.100664_bib13","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aan0241","article-title":"RNAi-based treatment of chronically infected patients and chimpanzees reveals that integrated hepatitis B virus DNA is a source of HBsAg","volume":"9","author":"Wooddell","year":"2017","journal-title":"Sci Transl Med"},{"key":"10.1016\/j.jhepr.2022.100664_bib14","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.jhep.2021.04.051","article-title":"Ubiquitous expression of HBsAg from integrated HBV DNA in patients with low viral load","volume":"75","author":"Meier","year":"2021","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100664_bib15","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.cld.2021.07.001","article-title":"Novel therapies that may cure chronic hepatitis B virus","volume":"25","author":"Loglio","year":"2021","journal-title":"Clin Liver Dis"},{"key":"10.1016\/j.jhepr.2022.100664_bib16","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1056\/NEJMoa0802878","article-title":"Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B","volume":"359","author":"Marcellin","year":"2008","journal-title":"N\u00a0Engl J Med"},{"key":"10.1016\/j.jhepr.2022.100664_bib17","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/hep.26277","article-title":"Efficacy of tenofovir disoproxil fumarate at 240 weeks in patients with chronic hepatitis B with high baseline viral load","volume":"58","author":"Gordon","year":"2013","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100664_bib18","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"67","year":"2017","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100664_bib19","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01695-20","article-title":"Characterization of hepatitis B precore\/core-related antigens","volume":"95","author":"Hong","year":"2021","journal-title":"J Virol"},{"key":"10.1016\/j.jhepr.2022.100664_bib20","article-title":"Multi-institutional TSA-amplified multiplexed immunofluorescence reproducibility evaluation (MITRE) study","volume":"9","author":"Taube","year":"2021","journal-title":"J\u00a0Immunother Cancer"},{"key":"10.1016\/j.jhepr.2022.100664_bib21","series-title":"Medical image computing and computer-assisted intervention \u2013 MICCAI 2015","first-page":"234","article-title":"U-Net: convolutional networks for biomedical image segmentation","author":"Ronneberger","year":"2015"},{"key":"10.1016\/j.jhepr.2022.100664_bib22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/hep.27381","article-title":"Serum hepatitis B virus RNA levels as an early predictor of hepatitis B e antigen seroconversion during treatment with polymerase inhibitors","volume":"61","author":"van B\u00f6mmel","year":"2015","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100664_bib23","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.jhep.2022.02.016","article-title":"Multi-parametric analysis of human livers reveals variation in intrahepatic inflammation across phases of chronic hepatitis B infection","volume":"77","author":"Montanari","year":"2022","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100664_bib24","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/hep.1840080408","article-title":"Correlation of hepatocyte HBsAg expression with virus replication and liver pathology","volume":"8","author":"Hsu","year":"1988","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100664_bib25","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1172\/JCI83339","article-title":"In situ analysis of intrahepatic virological events in chronic hepatitis B virus infection","volume":"126","author":"Zhang","year":"2016","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jhepr.2022.100664_bib26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/hep.1840040111","article-title":"Relationship between expression of hepatitis B virus antigens in isolated hepatocytes and autologous lymphocyte cytotoxicity in patients with chronic hepatitis B virus infection","volume":"4","author":"Naumov","year":"1984","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100664_bib27","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/S0168-8278(87)80060-0","article-title":"Biologic and prognostic significance of hepatocyte hepatitis B core antigen expressions in the natural course of chronic hepatitis B virus infection","volume":"5","author":"Hsu","year":"1987","journal-title":"J\u00a0Hepatol"},{"key":"10.1016\/j.jhepr.2022.100664_bib28","article-title":"Characterization of the liver immune microenvironment in liver biopsies from patients with chronic HBV infection","volume":"4","author":"van Buuren","year":"2022","journal-title":"JHEP Rep"},{"key":"10.1016\/j.jhepr.2022.100664_bib29","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1111\/j.1440-1746.2008.05416.x","article-title":"Correlation of hepatocyte expression of hepatitis B viral antigens with histological activity and viral titer in chronic hepatitis B virus infection: an immunohistochemical study","volume":"23","author":"Ramakrishna","year":"2008","journal-title":"J\u00a0Gastroenterol Hepatol"},{"key":"10.1016\/j.jhepr.2022.100664_bib30","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.3748\/wjg.v22.i12.3404","article-title":"Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma","volume":"22","author":"Safaie","year":"2016","journal-title":"World J Gastroenterol"},{"key":"10.1016\/j.jhepr.2022.100664_bib31","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\u00a0Virol"},{"key":"10.1016\/j.jhepr.2022.100664_bib32","doi-asserted-by":"crossref","first-page":"6255","DOI":"10.1128\/JVI.00346-14","article-title":"Support of the infectivity of hepatitis delta virus particles by the envelope proteins of different genotypes of hepatitis B virus","volume":"88","author":"Freitas","year":"2014","journal-title":"J\u00a0Virol"},{"key":"10.1016\/j.jhepr.2022.100664_bib33","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3390\/genes9070365","article-title":"Cellular genomic sites of hepatitis B virus DNA integration","volume":"9","author":"Budzinska","year":"2018","journal-title":"Genes (Basel)"},{"key":"10.1016\/j.jhepr.2022.100664_bib34","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1136\/jcp.38.4.393","article-title":"Widespread presence of cytoplasmic HBcAg in hepatitis B infected liver detected by improved immunochemical methods","volume":"38","author":"Gowans","year":"1985","journal-title":"J\u00a0Clin Pathol"},{"key":"10.1016\/j.jhepr.2022.100664_bib35","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3934\/medsci.2018.2.90","article-title":"Ground glass hepatocytes provide targets for therapy or prevention of hepatitis B virus-related hepatocellular carcinoma","volume":"5","author":"Chang","year":"2018","journal-title":"AIMS Med Sci"},{"key":"10.1016\/j.jhepr.2022.100664_bib36","doi-asserted-by":"crossref","first-page":"27724","DOI":"10.18632\/oncotarget.8388","article-title":"Resistance of ground glass hepatocytes to oral antivirals in chronic hepatitis B patients and implication for the development of hepatocellular carcinoma","volume":"7","author":"Tsai","year":"2016","journal-title":"Oncotarget"},{"key":"10.1016\/j.jhepr.2022.100664_bib37","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1053\/j.gastro.2021.12.286","article-title":"Inhibition of viral replication reduces transcriptionally active distinct hepatitis B virus integrations with implications on host gene dysregulation","volume":"162","author":"Hsu","year":"2022","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2022.100664_bib38","doi-asserted-by":"crossref","DOI":"10.1172\/JCI161818","article-title":"Integrated hepatitis B virus DNA maintains surface antigen production during antivirals","volume":"132","author":"Grudda","year":"2022","journal-title":"J\u00a0Clin Invest"},{"key":"10.1016\/j.jhepr.2022.100664_bib39","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0262516","article-title":"Ongoing viral replication and production of infectious virus in patients with chronic hepatitis B virus suppressed below the limit of quantitation on long-term nucleos(t)ide therapy","volume":"17","author":"Burdette","year":"2022","journal-title":"PLoS One"},{"key":"10.1016\/j.jhepr.2022.100664_bib40","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1053\/j.gastro.2004.03.018","article-title":"Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy","volume":"126","author":"Werle-Lapostolle","year":"2004","journal-title":"Gastroenterology"},{"key":"10.1016\/j.jhepr.2022.100664_bib41","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/hep.31240","article-title":"Rapid turnover of hepatitis B virus covalently closed circular DNA indicated by monitoring emergence and reversion of signature-mutation in treated chronic hepatitis B patients","volume":"73","author":"Huang","year":"2021","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100664_bib42","first-page":"416","article-title":"Export of intracellular HBsAg in chronic hepatitis B virus infection is related to viral replication","volume":"14","author":"Lau","year":"1991","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100664_bib43","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1002\/hep.23571","article-title":"Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers","volume":"51","author":"Thompson","year":"2010","journal-title":"Hepatology"},{"key":"10.1016\/j.jhepr.2022.100664_bib44","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/0016-5085(87)90863-8","article-title":"Intrahepatic distribution of hepatitis B surface\u00a0and\u00a0core antigens in chronic hepatitis B virus infection. Hepatocyte with\u00a0cytoplasmic\/membranous hepatitis B core antigen as a possible\u00a0target for immune hepatocytolysis","volume":"92","author":"Chu","year":"1987","journal-title":"Gastroenterology"}],"container-title":["JHEP Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555922002361?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589555922002361?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:32:14Z","timestamp":1762900334000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589555922002361"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["S2589555922002361"],"URL":"https:\/\/doi.org\/10.1016\/j.jhepr.2022.100664","relation":{},"ISSN":["2589-5559"],"issn-type":[{"value":"2589-5559","type":"print"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Intrahepatic quantification of HBV antigens in chronic hepatitis B reveals heterogeneity and treatment-mediated reductions in HBV core-positive cells","name":"articletitle","label":"Article Title"},{"value":"JHEP Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jhepr.2022.100664","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).","name":"copyright","label":"Copyright"}],"article-number":"100664"}}