{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T12:54:39Z","timestamp":1766408079108,"version":"3.41.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T00:00:00Z","timestamp":1627430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Most Chinese Blood Centers adopted mini pool (MP) nucleic acid testing (NAT) for HBV screening due to high cost of Individual donation (ID) NAT, and different proportions of MP-reactive but ID-non-reactive donations (MP+\/ID\u2212, defined as non-resolved donations) have been observed during daily donor screening process. Some of these non-resolved donations are occult HBV infections (OBIs), which pose potential risk of HBV transmission if they are not deferred. This study is aimed to further analyze these non-resolved donations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The non-resolved plasma samples were further analyzed by serological tests and various HBV DNA amplification assays including quantitative PCR (qPCR) and nested PCR amplifying the basic core and pre-core promoter regions (BCP\/PC; 295 base pairs) and HBsAg (S) region (496 base pairs). Molecular characterizations of HBV DNA+ non-resolved samples were determined by sequencing analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 17,226 MPs from 103,356 seronegative blood donations, 98 MPs were detected reactive for HBV. Fifty-six out of these 98 (57.1%) reactive MPs were resolved as HBV DNA+, but the remaining 42 pools (42.9%, 252 donations) were left non-resolved with a high rate (53.2%) of anti-HBc+. Surprisingly, among 42 non-resolved MPs, 17 contained one donation identified as OBIs by alternative NAT assays. Sequence analysis on HBV DNAs extracted from these OBI donations showed some key mutations in the S region that may lead to failure in HBsAg detection and vaccine escape.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A total of 53.2% of the non-resolved donations were anti-HBc+, and OBIs were identified in 40.5% of these non-resolved pools. Therefore, non-resolved donations with anti-HBc+ might pose potential risk for HBV transmission. Our present analysis indicates that anti-HBc testing in non-resolved donations should be used to identify OBIs in order to further increase blood safety in China.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.699217","type":"journal-article","created":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T10:15:50Z","timestamp":1627467350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["High Frequency Occult Hepatitis B Virus Infection Detected in Non-Resolved Donations Suggests the Requirement of Anti-HBc Test in Blood Donors in Southern China"],"prefix":"10.3389","volume":"12","author":[{"given":"Xianlin","family":"Ye","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Limin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.07.014","article-title":"Statements From the Taormina Expert Meeting on Occult Hepatitis B Virus Infection","volume":"49","author":"Raimondo","year":"2008","journal-title":"J Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.10.048","article-title":"Hepatitis B Virus Maintains its Prooncogenic Properties in the Case of Occult HBV Infection","volume":"126","author":"Pollicino","year":"2004","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2450\/2019.0182-19","article-title":"Occult Hepatitis B Infection Among Blood Donors From Yaound\u00e9, Cameroon","volume":"17","author":"Fopa","year":"2019","journal-title":"Blood Transfus"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-301281","article-title":"Occult Hepatitis B Infection in Blood Donors From South East Asia: Molecular Characterisation and Potential Mechanisms of Occurrence","volume":"61","author":"Candotti","year":"2012","journal-title":"Gut"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.05.009","article-title":"Influence of Mutations in Hepatitis B Virus Surface Protein on Viral Antigenicity and Phenotype in Occult HBV Strains From Blood Donors","volume":"57","author":"Huang","year":"2016","journal-title":"J Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.209148","article-title":"Prevalence of Occult Hepatitis B Infection in a Highly Endemic Area for Chronic Hepatitis B: A Study of a Large Blood Donor Population","volume":"59","author":"Yuen","year":"2006","journal-title":"Gut"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316490","article-title":"Multiple HBV Transfusion Transmissions From Undetected Occult Infections: Revising the Minimal Infectious Dose","volume":"68","author":"Candotti","year":"2019","journal-title":"Gut"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.06.016","article-title":"Poor Efficacy of Nucleic Acid Testing in Identifying Occult HBV Infection and Consequences for Safety of Blood Supply in Italy","volume":"63","author":"Spreafico","year":"2015","journal-title":"J Hepatol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1111\/j.1423-0410.2011.01506.x","article-title":"International Survey on NAT Testing of Blood Donations: Expanding Implementation and Yield From 1999 to 2009","volume":"102","author":"Roth","year":"2012","journal-title":"Vox Sang"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2010.02.004","article-title":"Analytical and Clinical Performance Evaluation of the Cobas TaqScreen MPX Test for Use on the Cobas s 201 System","volume":"165","author":"Ohhashi","year":"2010","journal-title":"J Virol Methods"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2008.01779.x","article-title":"Evaluation of the Roche Cobas s 201 System and Cobas TaqScreen Multiplex Test for Blood Screening: A European Multicenter Study","volume":"48","author":"Jarvis","year":"2008","journal-title":"Transfusion"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4215-9","article-title":"Nearly Half of Ultrio Plus NAT Nondiscriminated Reactive Blood Donors Were Identified as Occult HBV Infection in South China","volume":"19","author":"Ye","year":"2019","journal-title":"BMC Infect Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12653","article-title":"Comparison of Seven Hepatitis B Virus (HBV) Nucleic Acid Testing Assays in Selected Samples With Discrepant HBV Markers Results From United States Blood Donors","volume":"54","author":"Enjalbert","year":"2014","journal-title":"Transfusion"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00145-11","article-title":"Characterization of Occult Hepatitis B Virus Infection From Blood Donors in China","volume":"49","author":"Zheng","year":"2011","journal-title":"J Clin Microbiol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.11.004","article-title":"N-Glycosylation Mutations Within Hepatitis B Virus Surface","volume":"62","author":"Yu","year":"2014","journal-title":"J hepat"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13070","article-title":"HBV T1719G Mutation Reduced HBV Replication Through Mutant Enh II and Hbx Protein in Vitro","volume":"26","author":"Jiao","year":"2019","journal-title":"J Viral Hepat"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.tracli.2017.06.014","article-title":"Occult Hepatitis B Infection and Transfusion-Transmission Risk","volume":"24","author":"Candotti","year":"2017","journal-title":"Transfus Clin Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/vox.13045","article-title":"An Economic Reappraisal of Hepatitis B Virus Testing Strategy for Blood Donors in Taiwan","volume":"116","author":"Matanhire","year":"2021","journal-title":"Vox Sang"},{"key":"B19","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1111\/trf.12818","article-title":"What is The Meaning of a Nonresolved Viral Nucleic Acid Test-Reactive Minipool","volume":"55","author":"Wang","year":"2015","journal-title":"Transfusion"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2010.02804.x","article-title":"Refinement of a Viral Transmission Risk Model for Blood Donations in Seroconversion Window Phase Screened by Nucleic Acid Testing in Different Pool Sizes and Repeat Test Algorithms","volume":"51","author":"Weusten","year":"2011","journal-title":"Transfusion"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2007.01343.x","article-title":"Comparison of Two Automated Nucleic Acid Testing Systems for Simultaneous Detection of Human Immunodeficiency Virus and Hepatitis C Virus RNA and Hepatitis B Virus DNA","volume":"47","author":"Margaritis","year":"2007","journal-title":"Transfusion"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12096","article-title":"Infectivity of Blood Products From Donors With Occult Hepatitis B Virus Infection","volume":"53","author":"Allain","year":"2013","journal-title":"Transfusion"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2009.02322.x","article-title":"Infectivity of Human Immunodeficiency Virus-1, Hepatitis C Virus, and Hepatitis B Virus and Risk of Transmission by Transfusion","volume":"49","author":"Kleinman","year":"2009","journal-title":"Transfusion"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14050","article-title":"A Mathematical Model for Estimating Residual Transmission Risk of Occult Hepatitis B Virus Infection With Different Blood Safety Scenarios","volume":"57","author":"Weusten","year":"2017","journal-title":"Transfusion"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.2003.00541.x","article-title":"HIV Antibody Screening Remains Indispensable for Ensuring Viral Safety of Blood Components Despite NAT Implementation","volume":"43","author":"Laperche","year":"2013","journal-title":"Transfusion"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2009.02212.x","article-title":"Experience of Mandatory Nucleic Acid Testing (NAT) Screening Across All Blood Organizations in Germany: NAT Yield Versus Breakthrough Transmissions","volume":"49","author":"N\u00fcbling","year":"2009","journal-title":"Transfusion"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2012.03909.x","article-title":"Residual Risk of Transfusion Transmitted Hepatitis B Virus (HBV) Infection Caused by Blood Components Derived From Donors With Occult HBV Infection in Japan","volume":"53","author":"Taira","year":"2013","journal-title":"Transfusion"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2012.03909.x","article-title":"Hepatitis B Virus Infection and Transfusion Medicine: Science and the Occult","volume":"48","author":"Hollinger","year":"2008","journal-title":"Transfusion"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/trf.15393","article-title":"Optimal Titer of Anti-HBs in Blood Components Derived From Donors With Anti-HBc","volume":"59","author":"Hoshi","year":"2009","journal-title":"Transfusion"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.2001.41070878.x","article-title":"Analysis of HBV Infection After Blood Transfusion in Japan Through Investigation of a Comprehensive Donor Specimen Repository","volume":"41","author":"Matsumoto","year":"2001","journal-title":"Transfusion"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.02.016","article-title":"Anti-Hbs Positive Occult Hepatitis B Virus Carrier Blood Infectious in Two Transfusion Recipients","volume":"48","author":"Levicnik-Stezinar","year":"2008","journal-title":"J Hepatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/s0041-1345(99)00419-4","article-title":"Transmission of Hepatitis B by Transplantation of Livers From Donors Positive for Antibody to Hepatitis B Core Antigen","volume":"31","author":"Castells","year":"1999","journal-title":"Transplant Proc"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2008.04.017","article-title":"Characterization of Occult Hepatitis B Virus Form Blood Donors Carrying Genotype A2 or Genotype D Strains","volume":"49","author":"Candotti","year":"2008","journal-title":"J Hepatol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.jhep.2009.05.020","article-title":"Transfusion-Transmitted Hepatitis B Virus Infection","volume":"51","author":"Candotti","year":"2009","journal-title":"J Hepatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e32834bac10","article-title":"Challenges in Hepatitis B Detection Among Blood Donors","volume":"18","author":"Allain","year":"2011","journal-title":"Curr Opin Hematol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3148.2005.00551.x","article-title":"Acute Hepatitis B Infection Due to Erythrocyte Suspension Obtained From 'Anti-HBc Alone' Positive Donor","volume":"15","author":"Akcam","year":"2005","journal-title":"Transf Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131912","article-title":"Occult Hepatitis B Virus Infection in Nigerian Blood Donors and Hepatitis B Virus Transmission Risks","volume":"10","author":"Oluyinka","year":"2005","journal-title":"PloS One"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2010.002","article-title":"The Role of Anti-Core Antibody Response in the Detection of Occult Hepatitis B Virus Infection","volume":"48","author":"Urbani","year":"2010","journal-title":"Clin Chem Lab Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12218","article-title":"Transmission of Occult HBV Infection by ID-NAT Screened Blood","volume":"107","author":"Vermeulen","year":"2014","journal-title":"Vox Sang"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12198","article-title":"Infectivity of Blood Components From Donors With Occult Hepatitis B Infection \u2013 Results From an Australian Look Back Programme","volume":"108","author":"Seed","year":"2015","journal-title":"Vox Sang"},{"key":"B41","doi-asserted-by":"publisher","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":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-553X.2008.01092.x","article-title":"Sensitivity and Specificity of Anti-HBc Screening Assays \u2013 Which Assay Is Best for Blood Donor Screening","volume":"31","author":"Hourfar","year":"2009","journal-title":"Int J Lab Hematol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.tracli.2003.12.003","article-title":"Should HBV DNA NAT Replace HBsAg and\/or Anti-HBc Screening of Blood Donors","volume":"11","author":"Busch","year":"2004","journal-title":"Transfus Clin Biol"},{"key":"B44","doi-asserted-by":"publisher","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":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2013.08.005","article-title":"Six-Year Pilot Study on Nucleic Acid Testing for Blood Donations in China","volume":"49","author":"Ye","year":"2013","journal-title":"Trans Aphe Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.13303\/j.cjbt.issn.1004-549x.2014.02.0019","article-title":"Cost Benefit Analysis of 43 714 Donors Blood Nucleic Acid Testing Applied to Screening in Wuhan, China","volume":"27","author":"Cun","year":"2014","journal-title":"Chin J Blood Transfusion"},{"key":"B47","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1002\/hep.20748","article-title":"Functional Analysis of Hepatitis B Virus Reactivating in Hepatitis B Surface Antigen-Negative Individuals","volume":"42","author":"Hass","year":"2005","journal-title":"Hepatology"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2006.00874.x","article-title":"International Collaborative Study Proposal for the Characterization of Occult Hepatitis B Virus Infection Identified by Nucleic Acid or Anti-Hbc Screening","volume":"92","author":"Allain","year":"2007","journal-title":"Vox Sang"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.699217\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,28]],"date-time":"2021-07-28T10:15:54Z","timestamp":1627467354000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.699217\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,28]]},"references-count":48,"alternative-id":["10.3389\/fimmu.2021.699217"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.699217","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2021,7,28]]},"article-number":"699217"}}