血浆和全血中EBV-DNA诊断潜力的前瞻性评估。

A prospective evaluation of the diagnostic potential of EBV-DNA in plasma and whole blood.

作者信息

Ludvigsen Lene Ugilt Pagter, Andersen Annemette Sloth, Hamilton-Dutoit Stephen, Jensen-Fangel Søren, Bøttger Pernille, Handberg Kurt Jensen, Ivarsen Per, d'Amore Francesco, Bibby Bo Martin, Albertsen Birgitte Klug, Jespersen Bente, Thomsen Marianne Kragh

机构信息

Department of Renal Medicine, Aarhus University Hospital, Denmark; Department of Infectious Diseases, Odense University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.

Department of Clinical Microbiology, Aarhus University Hospital, Denmark.

出版信息

J Clin Virol. 2023 Oct;167:105579. doi: 10.1016/j.jcv.2023.105579. Epub 2023 Aug 30.

DOI:10.1016/j.jcv.2023.105579

PMID:37683299

Abstract

BACKGROUND

Quantitative polymerase chain reaction (qPCR) for Epstein-Barr virus (EBV)-DNA is an important diagnostic tool for EBV-associated disease, but interpretation of its clinical significance is challenging.

OBJECTIVES

We assessed the diagnostic and clinical performance of WHO-standardised qPCR for EBV-DNA (WHO EBV-qPCR) in plasma and whole blood (WB) for proven EBV disease in a prospectively accrued patient cohort.

STUDY DESIGN

Central Denmark Region patients, tested with WHO EBV-qPCR from November 2017 to March 2019, were screened for EBV disease. Incidence (IR) was estimated by Poisson regression. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for EBV-qPCR in plasma and WB. Risk of diagnostic latency was compared between patients with EBV-positive and EBV-negative lymphomas.

RESULTS

EBV disease was diagnosed in 95 of 1484 participants (IR: 16.3 per 1000 patientyears 95%CI; 13.3-19.9). Sensitivity and specificity of WHO EBV-qPCR in plasma was 82.4% (95% CI; 74.2-90.7%) and 87.8% (95% CI; 85.6-90%), yielding a PPV of 32.2% (95% CI; 24.9-39.5%) and NPV of 98.6% (95% CI; 97.7-99.5%) for proven EBV disease. Sensitivity and NPV were comparable in WB, while specificity and PPV decreased to 66.9% (95% CI; 60.6-73.1%) and 18.1% (95% CI; 7.5-28.7%). Risk of diagnostic latency was 2.3-fold (95% CI 1.4-4.1) higher for patients with EBV-positive compared with EBV-negative lymphomas.

CONCLUSIONS

WHO EBV-qPCR in plasma and WB have a low PPV but a high NPV for proven EBV disease. Implementation of WHO EBV-qPCR could improve interpretation and facilitate EBV-positive lymphoma diagnosis.

摘要

背景

针对爱泼斯坦-巴尔病毒（EBV）-DNA的定量聚合酶链反应（qPCR）是EBV相关疾病的重要诊断工具，但其临床意义的解读具有挑战性。

目的

我们评估了世界卫生组织标准化的血浆和全血（WB）EBV-DNA qPCR（WHO EBV-qPCR）在一个前瞻性纳入的患者队列中对确诊EBV疾病的诊断和临床性能。

研究设计

对2017年11月至2019年3月间接受WHO EBV-qPCR检测的丹麦中部地区患者进行EBV疾病筛查。发病率（IR）通过泊松回归估计。计算血浆和WB中EBV-qPCR的敏感性、特异性、阳性和阴性预测值（PPV、NPV）。比较EBV阳性和EBV阴性淋巴瘤患者的诊断延迟风险。

结果

1484名参与者中有95人被诊断为EBV疾病（IR：每1000患者年16.3例，95%CI；13.3 - 19.9）。血浆中WHO EBV-qPCR的敏感性和特异性分别为82.4%（95%CI；74.2 - 90.7%）和87.8%（95%CI；85.6 - 90%），对于确诊的EBV疾病，PPV为32.2%（95%CI；24.9 - 39.5%），NPV为98.6%（95%CI；97.7 - 99.5%）。WB中的敏感性和NPV相当，而特异性和PPV分别降至66.9%（95%CI；60.6 - 73.1%）和18.1%（95%CI；7.5 - 28.7%）。EBV阳性淋巴瘤患者的诊断延迟风险比EBV阴性淋巴瘤患者高2.3倍（95%CI 1.4 - 4.1）。