{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:43:47Z","timestamp":1792158227261,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","award":["ECTZ21574"],"award-info":[{"award-number":["ECTZ21574"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Blood donor screening occasionally identifies individuals with high HBV surface antigen (HBsAg) levels despite undetectable or extremely low HBV DNA. Molecular basis and transfusion risk of this discordant profile remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design and Methods<\/jats:title>\n                    <jats:p>Seventy\u2010five blood donors with HBsAg &gt;100\u2009IU\/mL and undetectable or very low HBV DNA (&lt;6\u2009IU\/mL), including 39 ID\u2010NAT\u2010nonreactive, were investigated. HBV DNA was further assessed using a second ID\u2010NAT assay, confirmatory PCR following virion concentration, and sequencing. Sequences were compared with those from genotype\u2010matched high\u2010viremia controls. Selected basic core promoter (BCP) and core mutations were introduced into 1.18\u2010mer replication\u2010competent Hepatitis B virus (HBV)\u00a0plasmids to assess effects on extracellular virion\u2010associated DNA production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four (5%) samples were nonreactive by the two ID\u2010NAT assays. HBV DNA was confirmed in all donors, often at unquantifiable levels, and all were anti\u2010HBc positive. No consistent molecular signature was identified. Heterogeneous, case\u2010specific mutations were detected in BCP, core, and PreS1, including variants predicted to affect pregenomic RNA transcription, encapsidation, or virion assembly, with no evidence of impaired polymerase activity. In vitro, selected BCP mutations significantly reduced extracellular HBV DNA without affecting HBsAg production. Most core mutations had minimal impact, although two strains carrying cN92T\/cM93T or cS170F showed reduced virion\u2010associated DNA. Some constructs exhibited impaired virion secretion or increased naked capsid production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HBsAg\u2010positive\/low\u2010DNA profile largely reflects chronic inactive infection with minimal viremia. Diverse regulatory and structural mutations may contribute in a multifactorial manner. Persistent viral genomes and residual replication support continued HBsAg screening where NAT sensitivity is suboptimal and anti\u2010HBc testing cannot be implemented.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.70334","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:22:11Z","timestamp":1784614931000},"page":"1993-2006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>Hepatitis B virus<\/scp>\n                    infection with high\n                    <scp>HBsAg<\/scp>\n                    and undetectable\n                    <scp>DNA<\/scp>\n                    levels in untreated blood donors: Viral mechanisms and transfusion safety implications"],"prefix":"10.1111","volume":"66","author":[{"given":"Maelenn Pa\u00efline","family":"Delcourt","sequence":"first","affiliation":[{"name":"Department of Blood Transmitted Agents National Institute of Blood Transfusion  Paris France"},{"name":"Institut Mondor\u2010(INSERM U955), Team \u201cViruses, Hepatology, Cancer\u201d  Cr\u00e9teil France"},{"name":"Department of Virology Henri Mondor Hospital (AP\u2010HP), University of Paris\u2010Est  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-4526","authenticated-orcid":false,"given":"Marion","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"The South African National Blood Service  Johannesburg Republic of South Africa"},{"name":"The University of the Free State  Bloemfontein Republic of South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Kopacz","sequence":"additional","affiliation":[{"name":"Department of Virology Institute of Haematology &amp; Transfusion Medicine  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Miletic","sequence":"additional","affiliation":[{"name":"Croatian Institute of Transfusion Medicine  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Saville","sequence":"additional","affiliation":[{"name":"The South African National Blood Service  Johannesburg Republic of South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Niederhauser","sequence":"additional","affiliation":[{"name":"Interregional Blood Transfusion SRC  Berne Switzerland"},{"name":"Institute for Infectious Diseases, University of Berne  Berne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0745-7559","authenticated-orcid":false,"given":"Jean\u2010Michel","family":"Pawlotsky","sequence":"additional","affiliation":[{"name":"Institut Mondor\u2010(INSERM U955), Team \u201cViruses, Hepatology, Cancer\u201d  Cr\u00e9teil France"},{"name":"Department of Virology Henri Mondor Hospital (AP\u2010HP), University of Paris\u2010Est  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syria","family":"Laperche","sequence":"additional","affiliation":[{"name":"Department of Blood Transmitted Agents National Institute of Blood Transfusion  Paris France"},{"name":"Etablissement Fran\u00e7ais du Sang  La Plaine Saint\u2010Denis France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-5373","authenticated-orcid":false,"given":"Daniel","family":"Candotti","sequence":"additional","affiliation":[{"name":"Department of Blood Transmitted Agents National Institute of Blood Transfusion  Paris France"},{"name":"Institut Mondor\u2010(INSERM U955), Team \u201cViruses, Hepatology, Cancer\u201d  Cr\u00e9teil France"},{"name":"Department of Virology Henri Mondor Hospital (AP\u2010HP), University of Paris\u2010Est  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2004.04055.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13990"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.13713"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.03.034"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13819"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14784"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15824"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2010.01.014"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2013.06.011"},{"issue":"1","key":"e_1_2_9_11_1","first-page":"8","article-title":"Alternative hepatitis B virus DNA confirmatory algorithm identified occult hepatitis B virus infection in Chinese blood donors with non\u2010discriminatory nucleic acid testing","volume":"20","author":"Deng X","year":"2022","journal-title":"Blood Transfus"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.04.017"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy270"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2019.1663130"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00272-18"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i1.65"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/v9030056"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.16137"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-017-0759-8"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00647-20"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01468-4"},{"key":"e_1_2_9_23_1","unstructured":"US Food and Drug Administration.Recommendations for testing blood donations for hepatitis B surface antigen. 2025. 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