Ma Chunxiang, Jiang Mingshan, Li Jiaxin, Zeng Zhen, Wu Yushan, Cheng Rui, Lin Hao, Pang Jiangmei, Yin Fang, Jia Yongbin, Li Lili, Zhang Hu
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China.
Centre for Inflammatory Bowel Disease, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Infect Microbiol. 2025 Jan 7;14:1526633. doi: 10.3389/fcimb.2024.1526633. eCollection 2024.
The prospective application of plasma Epstein-Barr virus (EBV) DNA load as a noninvasive measure of intestinal EBV infection remains unexplored. This study aims to identify ideal threshold levels for plasma EBV DNA loads in the diagnosis and outcome prediction of intestinal EBV infection, particularly in cases of primary intestinal lymphoproliferative diseases and inflammatory bowel disease (IBD).
Receiver operating characteristic (ROC) curves were examined to determine suitable thresholds for plasma EBV DNA load in diagnosing intestinal EBV infection and predicting its prognosis.
108 patients were retrospectively assigned to the test group, while 56 patients were included in the validation group. Plasma EBV DNA loads were significantly higher in the intestinal EBV infection group compared to the non-intestinal EBV infection group (Median: 2.02 × 10 copies/mL, interquartile range [IQR]: 5.49 × 10-6.34×10 copies/mL versus 4.2×10 copies/mL, IQR: 1.07 ×10-6.08×10 copies/mL; P < 0.0001). Plasma EBV DNA levels at 9.21×10 and 6.77×10 copies/mL proved beneficial for the identification and prognostication in intestinal EBV infection, respectively. Values of 0.82 and 0.71 were yielded by the area under the ROC curve (AUC) in the test cohort, corresponding to sensitivities of 84.38% (95% confidence interval [95%CI]: 68.25%-93.14%) and 87.5% (95%CI: 69%-95.66%), specificities of 83.33% (95%CI: 64.15%-93.32%) and 68.09% (95%CI: 53.83%-79.6%), positive predictive values (PPV) of 87.1% (95%CI: 71.15%-94.87%) and 58.33% (95%CI: 42.2%-72.86%), and positive likelihood ratios (LR) of 5.06 and 2.74 in the validation cohort, respectively. Furthermore, a plasma EBV DNA load of 5.4×10 copies/mL helped differentiate IBD with intestinal EBV infection from primary intestinal EBV-positive lymphoproliferative disorders (PIEBV+LPDs), achieving an AUC of 0.85 within the test cohort, as well as 85% sensitivity (95%CI: 63.96%-94.76%), 91.67% specificity (95%CI: 64.61%-99.57%), 94.44% PPV (95%CI: 74.24%-99.72%), and an LR of 10.2 in the validation cohort.
Plasma EBV DNA load demonstrates notable potential in distinguishing between different patient cohorts with intestinal EBV infection, although its sensitivity requires further optimization for clinical application.
血浆EB病毒(EBV)DNA载量作为肠道EBV感染的一种非侵入性检测指标的前瞻性应用尚未得到探索。本研究旨在确定血浆EBV DNA载量在肠道EBV感染诊断和预后预测中的理想阈值水平,特别是在原发性肠道淋巴增殖性疾病和炎症性肠病(IBD)病例中。
采用受试者工作特征(ROC)曲线来确定血浆EBV DNA载量在诊断肠道EBV感染及其预后预测中的合适阈值。
108例患者被回顾性纳入试验组,56例患者被纳入验证组。肠道EBV感染组的血浆EBV DNA载量显著高于非肠道EBV感染组(中位数:2.02×10拷贝/mL,四分位间距[IQR]:5.49×10 - 6.34×10拷贝/mL,而对照组为4.2×10拷贝/mL,IQR:1.07×10 - 6.08×10拷贝/mL;P<0.0001)。血浆EBV DNA水平分别为9.21×10和6.77×10拷贝/mL时,被证明分别有利于肠道EBV感染的识别和预后评估。试验队列中ROC曲线下面积(AUC)分别为0.82和0.71,对应的敏感度分别为84.38%(95%置信区间[95%CI]:68.25% - 93.14%)和87.5%(95%CI:69% - 95.66%),特异度分别为83.33%(95%CI:64.15% - 93.32%)和68.09%(95%CI:53.83% - 79.6%),阳性预测值(PPV)分别为87.1%(95%CI:71.15% - 94.87%)和58.33%(95%CI:42.2% - 72.86%),验证队列中的阳性似然比(LR)分别为5.06和2.74。此外,血浆EBV DNA载量为5.4×10拷贝/mL有助于区分合并肠道EBV感染的IBD与原发性肠道EBV阳性淋巴增殖性疾病(PIEBV + LPDs),在试验队列中的AUC为0.85,验证队列中的敏感度为85%(95%CI:63.96% - 94.76%),特异度为91.67%(95%CI:64.61% - 99.57%),PPV为94.44%(95%CI:74.24% - 99.72%),LR为10.2。
血浆EBV DNA载量在区分不同肠道EBV感染患者队列方面具有显著潜力,尽管其敏感度在临床应用中还需要进一步优化。