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Objective <p>To establish a machine learning (ML) model for the early diagnosis of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) based on clinical features and to utilize the Shapley Additive Explanations (SHAP) method to interpret the ML model, thereby providing reliable factors for diagnosing EBV-HLH.</p> Methods <p>We collected clinical data from 1,026 children with Epstein-Barr virus (EBV) infection who were hospitalized at Children’s Hospital of Soochow University from October 2017 to September 2024. First, we compared the clinical data of Epstein-Barr virus-associated infectious mononucleosis (EBV-IM) and EBV-HLH through univariate analysis and least absolute shrinkage and selection operator (LASSO) regression to select key features for machine learning training. Subsequently, we applied six machine learning algorithms and logistic regression to build diagnostic models, and the optimal model was selected based on multiple evaluation metrics. Finally, we utilized the Shapley Additive Explanations (SHAP) algorithm to clarify the importance of variables in the model to facilitate its application in clinical settings.</p> Results <p>Among the six machine learning models and logistic regression evaluated, the Extreme Gradient Boosting (XGBoost) model demonstrated the strongest discrimination ability, with an area under the receiver operating characteristic curve (AUC) of 0.9775, sensitivity of 0.9461 and specificity of 0.9784. The SHAP analysis indicated that the most important predictors for EBV-HLH were D-dimer, cervical lymphadenopathy (CLA), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and CD3 + CD4+ T cells.</p> Conclusions <p>The XGBoost model demonstrated excellent predictive performance for the early identification of EBV-HLH in children. Compared with other models, it achieved higher sensitivity and may serve as a promising decision-support tool pending external validation.</p> Clinical trial number <p>Not applicable.</p>

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Development and validation of machine learning models for early diagnosis of hemophagocytic lymphohistiocytosis in pediatric Epstein–Barr virus infection

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月27日

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  • Yingying Ye,
  • Yuqin Li,
  • Yuewen Su,
  • Meng Cao,
  • Jiaxue Liu,
  • Jiaying Ding,
  • Shaoyan Hu,
  • Jianmei Tian,
  • Weifang Zhou

摘要

Objective

To establish a machine learning (ML) model for the early diagnosis of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) based on clinical features and to utilize the Shapley Additive Explanations (SHAP) method to interpret the ML model, thereby providing reliable factors for diagnosing EBV-HLH.

Methods

We collected clinical data from 1,026 children with Epstein-Barr virus (EBV) infection who were hospitalized at Children’s Hospital of Soochow University from October 2017 to September 2024. First, we compared the clinical data of Epstein-Barr virus-associated infectious mononucleosis (EBV-IM) and EBV-HLH through univariate analysis and least absolute shrinkage and selection operator (LASSO) regression to select key features for machine learning training. Subsequently, we applied six machine learning algorithms and logistic regression to build diagnostic models, and the optimal model was selected based on multiple evaluation metrics. Finally, we utilized the Shapley Additive Explanations (SHAP) algorithm to clarify the importance of variables in the model to facilitate its application in clinical settings.

Results

Among the six machine learning models and logistic regression evaluated, the Extreme Gradient Boosting (XGBoost) model demonstrated the strongest discrimination ability, with an area under the receiver operating characteristic curve (AUC) of 0.9775, sensitivity of 0.9461 and specificity of 0.9784. The SHAP analysis indicated that the most important predictors for EBV-HLH were D-dimer, cervical lymphadenopathy (CLA), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and CD3 + CD4+ T cells.

Conclusions

The XGBoost model demonstrated excellent predictive performance for the early identification of EBV-HLH in children. Compared with other models, it achieved higher sensitivity and may serve as a promising decision-support tool pending external validation.

Clinical trial number

Not applicable.