{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:06:48Z","timestamp":1789657608514,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009210","name":"Food and Drug Administration","doi-asserted-by":"publisher","award":["Z01 BP02029"],"award-info":[{"award-number":["Z01 BP02029"]}],"id":[{"id":"10.13039\/100009210","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AA031412"],"award-info":[{"award-number":["R21 AA031412"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI139954"],"award-info":[{"award-number":["R21 AI139954"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI179019"],"award-info":[{"award-number":["R01 AI179019"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 AI186383"],"award-info":[{"award-number":["R21 AI186383"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PhoenixBio Research Grant"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Characterize hepatitis B virus (HBV) isolates from deferred blood donors identified by routine blood screening and confirmatory tests in the United States, using virological, serological, and biochemical methods, and evaluate their infectivity in human hepatocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Forty-six hepatitis B surface antigen (HBsAg)-positive plasma samples, including 32 reactive and 14 nonreactive for anti-HBV core (anti-HBc) were identified by blood donation testing and further analyzed for hepatitis B e antigen (HBeAg)\/anti-HBe, liver disease markers (alanine aminotransferase and aspartate aminotransferase), and sequencing to determine virus genotype. To evaluate virus infectivity, plasma was used to inoculate humanized liver chimeric mouse-derived human hepatocytes (HLCM-HH). HBV DNA and HBsAg were monitored in culture media over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Subjects with confirmed positive screening tests for HBV fell into 2 groups: (1) older, predominantly Caucasian or African American, anti-HBc nonreactive and genotype A, who had successfully donated blood on a previous occasion when they tested negative for HBV, suggesting recent horizontal transmission, and (2) younger, predominantly Asian, anti-HBc reactive with genotypes B or C, attempting to donate for the first time, suggesting distant vertical transmission. HBV from all samples could infect and replicate in HLCM-HH cultures as measured by DNA. Infectivity could be blocked by incubating with anti-HBV immunoglobulin. Kinetics of DNA accumulation suggested more robust replication of viruses from anti-HBc nonreactive plasma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Analyses of plasma samples from individuals with HBV identified 2 groups differing in age, race, HBV genotype, and likely transmission route. HBV from anti-HBc nonreactive samples showed greater replicative fitness in HLCM-HH cultures compared to anti-HBc reactive samples.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiag400","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:15:33Z","timestamp":1785323733000},"source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Hepatitis B Virus in Blood Donors Who Were Disqualified Based on Testing: Genotype Distribution, Infectivity, and Replicative Fitness in Human Hepatocytes"],"prefix":"10.1093","author":[{"given":"Rana","family":"Eltahan","sequence":"first","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-1476","authenticated-orcid":false,"given":"Bryan J","family":"Visser","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santanu","family":"Biswas","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Ishida","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California , Los Angeles, California ,","place":["USA"]},{"name":"Research and Development Department, PhoenixBio, Co., Ltd , Higashi-Hiroshima, Hiroshima ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaelle","family":"Fares-Gusmao","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4672-0735","authenticated-orcid":false,"given":"Jiangqin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakthivel","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7548-405X","authenticated-orcid":false,"given":"Alysia","family":"Scott","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0570-0530","authenticated-orcid":false,"given":"Annabel","family":"Tiong","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California , Los Angeles, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Krysztof","sequence":"additional","affiliation":[{"name":"American Red Cross Biomedical Services, Medical and Scientific Office , Washington, District of Columbia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7735-8420","authenticated-orcid":false,"given":"Laura","family":"Tonnetti","sequence":"additional","affiliation":[{"name":"American Red Cross Biomedical Services, Medical and Scientific Office , Washington, District of Columbia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2328-626X","authenticated-orcid":false,"given":"Anne","family":"Eder","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4632-4751","authenticated-orcid":false,"given":"Carlos H","family":"Villa","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6165-664X","authenticated-orcid":false,"given":"Takeshi","family":"Saito","sequence":"additional","affiliation":[{"name":"Division of Gastrointestinal and Liver Diseases, Department of Medicine, Keck School of Medicine, University of Southern California , Los Angeles, California ,","place":["USA"]},{"name":"Department of Immunology and Immune Therapeutics, Keck School of Medicine, University of Southern California"},{"name":"Department of Pathology, Keck School of Medicine, University of Southern California , Los Angeles, California ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3497-5087","authenticated-orcid":false,"given":"David R","family":"McGivern","sequence":"additional","affiliation":[{"name":"Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food, and Drug Administration , Silver Spring, Maryland ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"2026091710170329700_jiag400-B1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1111\/jvh.13982","article-title":"Modelling the potential impact of global hepatitis B vaccination on the burden of chronic hepatitis B in the United States","volume":"31","author":"Hutton","year":"2024","journal-title":"J Viral Hepat"},{"key":"2026091710170329700_jiag400-B2","doi-asserted-by":"crossref","DOI":"10.54394\/CJQU6666","volume-title":"Global hepatitis report 2024: action for access in low- and middle-income countries","author":"World Health Organization","year":"2024"},{"key":"2026091710170329700_jiag400-B3","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a021410","article-title":"Hepatitis B virus epidemiology","volume":"5","author":"MacLachlan","year":"2015","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2026091710170329700_jiag400-B4","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/S0140-6736(22)01468-4","article-title":"Hepatitis B","volume":"401","author":"Jeng","year":"2023","journal-title":"Lancet"},{"key":"2026091710170329700_jiag400-B5"},{"key":"2026091710170329700_jiag400-B6","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1111\/trf.18398","article-title":"Incidence and window period residual risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in United States blood donations, 2017 to 2023: the transfusion-transmissible infections monitoring system","volume":"65","author":"Huseynova","year":"2025","journal-title":"Transfusion"},{"key":"2026091710170329700_jiag400-B7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/cld.728","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"12","author":"Terrault","year":"2018","journal-title":"Clin Liver Dis (Hoboken)"},{"key":"2026091710170329700_jiag400-B8","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 Hepatol"},{"key":"2026091710170329700_jiag400-B9","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0016-5085(03)00895-3","article-title":"Hepatitis B virus genotypes in the United States: results of a nationwide study","volume":"125","author":"Chu","year":"2003","journal-title":"Gastroenterology"},{"key":"2026091710170329700_jiag400-B10","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1093\/infdis\/jir862","article-title":"Genetic diversity of recently acquired and prevalent HIV, hepatitis B virus, and hepatitis C virus infections in US blood donors","volume":"205","author":"Delwart","year":"2012","journal-title":"J Infect Dis"},{"key":"2026091710170329700_jiag400-B11","doi-asserted-by":"crossref","DOI":"10.1016\/j.tmrv.2023.150769","article-title":"Leveraging donor populations to study the epidemiology and pathogenesis of transfusion-transmitted and emerging infectious diseases","volume":"37","author":"Bloch","year":"2023","journal-title":"Transfus Med Rev"},{"key":"2026091710170329700_jiag400-B12","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.3390\/life13071527","article-title":"Cell culture systems for studying hepatitis B and hepatitis D virus infections","volume":"13","author":"Lee","year":"2023","journal-title":"Life-Basel"},{"key":"2026091710170329700_jiag400-B13","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.162404","article-title":"Persistent hepatic IFN system activation in HBV-HDV infection determines viral replication dynamics and therapeutic response","volume":"8","author":"Chida","year":"2023","journal-title":"JCI Insight"},{"key":"2026091710170329700_jiag400-B14","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202201292RR","article-title":"Long-term cell fate and functional maintenance of human hepatocyte through stepwise culture configuration","volume":"37","author":"Sugahara","year":"2023","journal-title":"FASEB J"},{"key":"2026091710170329700_jiag400-B15","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.jhep.2021.07.030","article-title":"Infection courses, virological features and IFN-alpha responses of HBV genotypes in cell culture and animal models","volume":"75","author":"Zhang","year":"2021","journal-title":"J Hepatol"},{"key":"2026091710170329700_jiag400-B16","article-title":"Hepatitis B virus genotypes A1 and A2 have distinct replication phenotypes due to polymorphisms in the HBx gene","volume":"21","author":"Zhang","year":"2025","journal-title":"PLoS Pathog"},{"key":"2026091710170329700_jiag400-B17","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jcv.2012.01.003","article-title":"Variable capacity of 13 hepatitis B virus surface antigen assays for the detection of HBsAg mutants in blood samples","volume":"53","author":"Servant-Delmas","year":"2012","journal-title":"J Clin Virol"},{"key":"2026091710170329700_jiag400-B18","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1056\/NEJMoa1007644","article-title":"Nucleic acid testing to detect HBV infection in blood donors","volume":"364","author":"Stramer","year":"2011","journal-title":"N Engl J Med"},{"key":"2026091710170329700_jiag400-B19","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1111\/trf.14784","article-title":"Blood donor testing for hepatitis B virus in the United States: is there a case for continuation of hepatitis B surface antigen detection?","volume":"58","author":"Dodd","year":"2018","journal-title":"Transfusion"},{"key":"2026091710170329700_jiag400-B20","doi-asserted-by":"crossref","DOI":"10.1097\/MD.0000000000004618","article-title":"New universal primers for genotyping and resistance detection of low HBV DNA levels","volume":"95","author":"Tong","year":"2016","journal-title":"Medicine (Baltimore)"},{"key":"2026091710170329700_jiag400-B21"},{"key":"2026091710170329700_jiag400-B22","article-title":"Modeling of hepatitis B virus kinetics and accumulation of cccDNA in primary human hepatocytes","volume":"7","author":"Shekhtman","year":"2025","journal-title":"JHEP Rep"},{"key":"2026091710170329700_jiag400-B23","doi-asserted-by":"crossref","DOI":"10.1128\/jvi.00927-25","article-title":"Modeling of hepatitis B virus infection spread in primary human hepatocytes","volume":"99","author":"Shi","year":"2025","journal-title":"J Virol"},{"key":"2026091710170329700_jiag400-B24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.cgh.2014.06.028","article-title":"Characteristics of adults in the hepatitis B research network in North America reflect their country of origin and hepatitis B virus genotype","volume":"13","author":"Ghany","year":"2015","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2026091710170329700_jiag400-B25","author":"Centers for Disease Control and Prevention"},{"key":"2026091710170329700_jiag400-B26","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.15585\/mmwr.mm7244a3","article-title":"Vaccination coverage by age 24 months among children born in 2019 and 2020\u2014National Immunization Survey-Child, United States, 2020\u20132022","volume":"72","author":"Hill","year":"2023","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2026091710170329700_jiag400-B27","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1093\/cid\/cir495","article-title":"Genotypic distribution of hepatitis B virus (HBV) among acute cases of HBV infection, selected United States counties, 1999\u20132005","volume":"53","author":"Teshale","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2026091710170329700_jiag400-B28","doi-asserted-by":"crossref","first-page":"13971","DOI":"10.1128\/JVI.01594-14","article-title":"Recent population expansions of hepatitis B virus in the United States","volume":"88","author":"Ramachandran","year":"2014","journal-title":"J Virol"},{"key":"2026091710170329700_jiag400-B29","doi-asserted-by":"crossref","first-page":"477","DOI":"10.15585\/mmwr.mm7113a1","article-title":"Universal hepatitis B vaccination in adults aged 19\u201359 years: updated recommendations of the advisory committee on immunization practices\u2014United States, 2022","volume":"71","author":"Weng","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2026091710170329700_jiag400-B30","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.cgh.2022.09.004","article-title":"Acute hepatitis B virus infection in North American adults","volume":"21","author":"Sterling","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2026091710170329700_jiag400-B31","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.virol.2017.12.011","article-title":"Phylogenetic analysis reveals three distinct epidemiological profiles in Dutch and Flemish blood donors with hepatitis B virus infection","volume":"515","author":"van de Laar","year":"2018","journal-title":"Virology"},{"key":"2026091710170329700_jiag400-B32","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1111\/trf.18357","article-title":"Assessing hepatitis B virus infectivity in blood components following pathogen reduction using a human hepatocyte model","volume":"65","author":"Visser","year":"2025","journal-title":"Transfusion"},{"key":"2026091710170329700_jiag400-B33","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.jhep.2019.08.022","article-title":"High tolerance of hepatitis B virus to thermal disinfection","volume":"71","author":"Konig","year":"2019","journal-title":"J Hepatol"},{"key":"2026091710170329700_jiag400-B34","doi-asserted-by":"crossref","DOI":"10.1097\/HC9.0000000000000047","article-title":"Evolutional transition of HBV genome during the persistent infection determined by single-molecule real-time sequencing","volume":"7","author":"Arasawa","year":"2023","journal-title":"Hepatol Commun"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag400\/70407881\/jiag400.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag400\/70407881\/jiag400.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:17:12Z","timestamp":1789654632000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/advance-article\/doi\/10.1093\/infdis\/jiag400\/8748170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":34,"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiag400","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"article-number":"jiag400"}}