Development and validation of a risk stratification score for hemophagocytic syndrome in chronic active Epstein-Barr virus infection: A 10-year retrospective cohort study

IF 4.8 3区医学 Q1 INFECTIOUS DISEASES

Journal of Infection and Public Health Pub Date : 2026-03-01 Epub Date: 2025-11-19 DOI:10.1016/j.jiph.2025.103061

Fei Hu , Jiayi Zhan , Meijuan Peng , Haifeng Hu , Xuyang Zheng , Danfeng Ren , Rui Li , Hong Du , Wen Tian , Zhanhu Bi , Denghui Yu , Hongkai Xu , Xiaofei Yang , Yan Liang , Fangfang Li , Jingtao Hou , Yingli He , Jianqi Lian

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引用次数: 0

Abstract

Objective

This study aims to identify risk factors for the development of hemophagocytic lymphohistiocytosis (HLH) within three years among patients with chronic active Epstein-Barr virus infection (CAEBV) and to construct a risk stratification score.

Methods

A retrospective cohort study was conducted involving 165 patients with CAEBV admitted to two infectious disease centers in Northwest China between January 2012 and December 2022, through which we identified independent risk factors for HLH. Cox regression was utilized to establish the nomogram model and generate the risk stratification score. The discrimination and clinical utility of both the nomogram and score models were subsequently assessed using calibration plots, receiver operating characteristic (ROC) curves, decision curve analysis (DCA), and cross-validation.

Results

Among the 165 patients, 98 (59.4 %) developed HLH within three years. The median progression time was 405 days (IQR: 217, 740), with cumulative incidence rates of HLH at 1, 2, and 3 years of 41.3 %, 56.1 %, and 65.9 %, respectively. Five independent predictors were identified: cytopenia (HR: 1.70, 95 % CI: 1.07–2.70), EBV-DNA load in plasma (HR: 2.02, 95 % CI: 1.46–2.80), alanine aminotransferase (HR: 1.34, 95 % CI: 1.12–1.60), ferritin (HR: 1.01, 95 % CI: 1.01–1.01), and triglycerides (HR: 1.21, 95 % CI: 1.05–1.38). Both the nomogram and simplified score model demonstrated excellent discrimination (AUC > 0.7) and reliable calibration within a 3-year timeframe. The score model exhibited predictive power comparable to the nomogram, as indicated by net reclassification index and integrated discrimination index analyses.

Conclusion

The validated nomogram and score model facilitate rapid HLH risk stratification in CAEBV patients, supporting clinical risk assessment and early intervention.

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慢性活动性eb病毒感染中噬血细胞综合征风险分层评分的建立和验证：一项10年回顾性队列研究

目的探讨慢性活动性eb病毒感染（CAEBV）患者3年内发生嗜血球性淋巴组织细胞增生症（HLH）的危险因素，并建立危险分层评分。方法对2012年1月至2022年12月在中国西北地区两家传染病中心收治的165例CAEBV患者进行回顾性队列研究，确定HLH的独立危险因素。采用Cox回归建立nomogram模型，生成风险分层评分。随后，通过校准图、受试者工作特征（ROC）曲线、决策曲线分析（DCA）和交叉验证来评估nomogram和scoring模型的辨别性和临床实用性。结果165例患者中，98例（59.4 %）在3年内发生HLH。中位进展时间为405天（IQR: 217、740），1年、2年和3年的HLH累积发病率分别为41.3% %、56.1% %和65.9% %。确定了5个独立的预测因子：细胞减少症（HR: 1.70, 95 % CI: 1.07-2.70）、血浆EBV-DNA负荷（HR: 2.02, 95 % CI: 1.46-2.80）、丙氨酸转氨酶（HR: 1.34, 95 % CI: 1.12-1.60）、铁蛋白（HR: 1.01, 95 % CI: 1.01 - 1.01）和甘油三酯（HR: 1.21, 95 % CI: 1.05-1.38）。模态图和简化评分模型均表现出良好的判别性（AUC > 0.7）和3年时间框架内可靠的校准。从净重分类指数和综合判别指数分析可以看出，得分模型的预测能力与nomogram相当。结论经验证的nomogram和scoring model有助于快速对CAEBV患者进行HLH风险分层，为临床风险评估和早期干预提供支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Infection and Public Health PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH -INFECTIOUS DISEASES

CiteScore

13.10

自引率

1.50%

发文量

203

审稿时长

96 days

期刊介绍： The Journal of Infection and Public Health, first official journal of the Saudi Arabian Ministry of National Guard Health Affairs, King Saud Bin Abdulaziz University for Health Sciences and the Saudi Association for Public Health, aims to be the foremost scientific, peer-reviewed journal encompassing infection prevention and control, microbiology, infectious diseases, public health and the application of healthcare epidemiology to the evaluation of health outcomes. The point of view of the journal is that infection and public health are closely intertwined and that advances in one area will have positive consequences on the other. The journal will be useful to all health professionals who are partners in the management of patients with communicable diseases, keeping them up to date. The journal is proud to have an international and diverse editorial board that will assist and facilitate the publication of articles that reflect a global view on infection control and public health, as well as emphasizing our focus on supporting the needs of public health practitioners. It is our aim to improve healthcare by reducing risk of infection and related adverse outcomes by critical review, selection, and dissemination of new and relevant information in the field of infection control, public health and infectious diseases in all healthcare settings and the community.