Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Department of Infection, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Rev Med Virol. 2024 Mar;34(2):e2525. doi: 10.1002/rmv.2525.
Blood transfusion is a vital procedure, where transfusion-transmitted infection of hepatitis B virus (HBV) remains an important issue, especially from blood donors with occult hepatitis B virus infection (OBI). 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-core antibody assays defer almost all potentially infectious donations but have low specificity, and titres of anti-surface 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-genomic RNA and HBV core-related antigen, immunological HBV biomarkers of T-cell 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-transmitted HBV infection without compromising the sustainability of blood supplies.
输血是一项至关重要的程序，其中乙型肝炎病毒（HBV）的输血传播感染仍然是一个重要问题，特别是对于隐匿性乙型肝炎病毒感染（OBI）的献血者。隐匿性乙型肝炎病毒感染是一种复杂的实体，使用替代血液生物标志物来检测肝内病毒转录活性非常困难，需要不断改进用于筛选的一系列测试。本综述旨在批判性地评估当前血液生物标志物在识别 OBI 供体方面的最新进展，并讨论可能在未来诊断实践中引入的新型 HBV 标志物。检测低水平 HBV 表面抗原、突变体和复合物的挑战需要超灵敏的多价解离测定，而 HBV DNA 检测需要提高灵敏度，但会降低可及性。抗核心抗体检测会使几乎所有潜在的传染性供体都推迟，但特异性低，并且能够预防感染性的抗表面抗体的效价定义不佳，敏感性也不理想。这些传统血液 HBV 标志物所面临的挑战迫切需要替代生物标志物，以帮助我们更好地了解 OBI。新兴的病毒生物标志物，如前基因组 RNA 和 HBV 核心相关抗原、T 细胞反应和细胞因子水平的免疫 HBV 生物标志物，以及 microRNA 和人类白细胞抗原分子的宿主生物标志物，为更准确地评估肝内活性提供了潜在的进展。对这些标志物的进一步研究可能会发现使用各种新型和传统血液 HBV 标志物进行定量的 OBI 最佳诊断算法。解决本综述中确定的关键知识空白将降低输血传播 HBV 感染的残余风险，而不会影响血液供应的可持续性。
