{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T12:20:47Z","timestamp":1772713247861,"version":"3.50.1"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01 AI138810"],"award-info":[{"award-number":["R01 AI138810"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01 AI116868"],"award-info":[{"award-number":["R01 AI116868"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01 OD011095"],"award-info":[{"award-number":["R01 OD011095"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["T32 CA193145"],"award-info":[{"award-number":["T32 CA193145"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["K24 DA034621"],"award-info":[{"award-number":["K24 DA034621"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01 DK094818"],"award-info":[{"award-number":["R01 DK094818"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Nucleos(t)ide analogues (NUCs) rarely cure chronic hepatitis B (CHB) because they do not eliminate covalently closed circular deoxyribonucleic acid, the stable replication template. In hepatitis B e antigen (HBeAg)-positive CHB during NUCs, HBV-infected cells decline slowly and are transcriptionally silenced. Whether these occur in HBeAg-negative CHB is unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using paired liver biopsies separated by 2.7\u20133.7 years in 4 males with HIV and HBeAg-negative CHB at both biopsies and 1 male with HIV who underwent HBeAg seroconversion between biopsies, we quantified amounts of viral nucleic acids in hundreds of individual hepatocytes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the 4 persistently HBeAg-negative participants, HBV-infected hepatocytes ranged from 6.2% to 17.7% (biopsy 1) and significantly declined in 3 of 4 by biopsy 2. In the HBeAg seroconverter, the proportion was 97.4% (biopsy 1) and declined to 81.9% at biopsy 2 (P &amp;lt; .05). We extrapolated that HBV eradication with NUCs would take &amp;gt;100 years. At biopsy 1 in the persistently HBeAg-negative participants, 23%\u201356.8% of infected hepatocytes were transcriptionally inactive\u2014higher than we observed in HBeAg-positive CHB\u2014and significantly declined in 1 of 4 at biopsy 2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In HBeAg-negative CHB on NUCs, the negligible decline in infected hepatocytes is similar to HBeAg-positive CHB, supporting the need for more potent therapeutics to achieve functional cure.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad124","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T12:04:09Z","timestamp":1683029049000},"page":"1219-1226","source":"Crossref","is-referenced-by-count":8,"title":["Hepatitis B e Antigen-Negative Single Hepatocyte Analysis Shows Transcriptional Silencing and Slow Decay of Infected Cells With Treatment"],"prefix":"10.1093","volume":"228","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8851-8319","authenticated-orcid":false,"given":"Chloe L","family":"Thio","sequence":"first","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"},{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maraake","family":"Taddese","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmeen","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina","family":"Zambo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruy M","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Los Alamos National Laboratory , Los Alamos, New Mexico , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanner","family":"Grudda","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health , Baltimore, Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S","family":"Sulkowski","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard K","family":"Sterling","sequence":"additional","affiliation":[{"name":"Divison of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University , Richmond, Virginia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal and Hepatic Pathology, Joint Pathology Center , Silver Spring, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric D","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyon S","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwin","family":"Balagopal","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,5,2]]},"reference":[{"key":"2023110719191747600_jiad124-B1","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","author":"Lampertico","year":"2017","journal-title":"J Hepatol"},{"key":"2023110719191747600_jiad124-B2","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.jhep.2020.11.003","article-title":"Transition to HBeAg-negative chronic hepatitis B virus infection is associated with reduced cccDNA transcriptional 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