Risk Prediction of Liver Injury in Pediatric Tuberculosis Treatment: Development of an Automated Machine Learning Model

Purpose: Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions related to first-line antituberculosis drugs in pediatric tuberculosis patients. This study aims to develop an automatic machine learning (AutoML) model for predicting the risk of anti-tuberculosis drug-induced liver injury (ATB-DILI) in children. Methods: A retrospective study was performed on the clinical data and therapeutic drug monitoring (TDM) results of children initially treated for tuberculosis at the affiliated Changsha Central Hospital of University of South China. After the features were screened by univariate risk factor analysis, AutoML technology was used to establish predictive models. The area under the receiver operating characteristic curve (AUC) was used to evaluate model's performance, and then the TreeShap algorithm was employed to interpret the variable contributions. Results: A total of 184 children were enrolled in this study, of whom 19 (10.33%) developed ATB-DILI. Univariate analysis showed that seven variables were risk factors for ATB-DILI, including the plasma peak concentration (Cmax) of rifampicin, body mass index (BMI), alanine aminotransferase, total bilirubin, total bile acids, aspartate aminotransferase and creatinine. Among the numerous predictive models constructed by the "H2O" AutoML platform, the gradient boost machine (GBM) model exhibited the superior performance with AUCs of 0.838 and 0.784 on the training and testing sets, respectively. The TreeShap algorithm showed that C max of rifampicin and BMI were important features that affect the AutoML model's performance. Conclusion: The GBM model established by AutoML technology shows high predictive accuracy and interpretability for ATB-DILI in children. The prediction model can assist clinicians to implement timely interventions and mitigation strategies, and formulate personalized medication regimens, thereby minimizing potential harm to high-risk children of ATB-DILI.