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Occult hepatitis B virus infection is a complex entity to detect using surrogate blood biomarkers for intrahepatic viral transcriptional activity, requiring a continually refined battery of tests utilised for screening. This review aims to critically evaluate the latest advances in the current blood biomarkers to guide the identification of OBI donors and discuss novel HBV markers that could be introduced in future diagnostic practice. Challenges in detecting low HBV surface antigen levels, mutants, and complexes necessitate ultrasensitive multivalent dissociation assays, whilst HBV DNA testing requires improved sensitivity but worsens inaccessibility. Anti\u2010core antibody assays defer almost all potentially infectious donations but have low specificity, and titres of anti\u2010surface antibodies that prevent infectivity are poorly defined with suboptimal sensitivity. The challenges associated with these traditional blood HBV markers create an urgent need for alternative biomarkers that would help us better understand the OBI. Emerging viral biomarkers, such as pre\u2010genomic RNA and HBV core\u2010related antigen, immunological HBV biomarkers of T\u2010cell reactivity and cytokine levels, and host biomarkers of microRNA and human leucocyte antigen molecules, present potential advances to gauge intrahepatic activity more accurately. Further studies on these markers may uncover an optimal diagnostic algorithm for OBI using quantification of various novel and traditional blood HBV markers. Addressing critical knowledge gaps identified in this review would decrease the residual risk of transfusion\u2010transmitted HBV infection without compromising the sustainability of blood supplies.<\/jats:p>","DOI":"10.1002\/rmv.2525","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T06:22:47Z","timestamp":1708410167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biomarkers of transfusion transmitted occult hepatitis B\u00a0virus infection: Where are we and what next?"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-7917","authenticated-orcid":false,"given":"Michael X.","family":"Fu","sequence":"first","affiliation":[{"name":"Nuffield Department of Medicine University of Oxford  Oxford 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