Construction and Validation of a Predictive Model for the Risk of Anti‐Tuberculosis Drug‐Induced Liver Injury Based on Machine Learning Algorithms

Anti-tuberculosis drug-induced liver injury (ATLI) is the most harmful to anti-tuberculosis (TB) treatment. This study aims to construct and validate a binary ATLI risk prediction model based on clinical data through seven machine learning algorithms (logistic regression, decision tree, support vector machine, random forest, gradient boosting decision tree, extreme gradient boosting, and light gradient boosting machine [LightGBM]). A retrospective cohort of 2356 TB patients followed between January 2017 and December 2024 was used to develop and evaluate the prediction model. Random undersampling was performed to address class imbalance problem. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and retained 27 of 31 original features. Seven ML algorithms were trained and the LightGBM model demonstrated optimal performance in testing set based on the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity (AUC = 0.789, sensitivity = 0.734, and specificity = 0.706). The model exhibited optimal simplicity and stability when incorporating the 8-feature combination comprising baseline high-density lipoprotein cholesterol (HDLC), γ-glutamyl transpeptidase (GGT), triglycerides, total cholesterol (TCHOL), uric acid, total bilirubin (TBIL), globulin (GLB), and liver disease history (AUC = 0.764, sensitivity = 0.758, and specificity = 0.610), and Shapely additive explanations analysis also revealed that these variables were the most influential contributors. The optimal model maintained robust predictive ability in the external validation cohort (AUC = 0.721, sensitivity = 0.828, and specificity = 0.604). This study determined that the combination of baseline HDLC, GGT, triglycerides, total cholesterol (TCHOL), uric acid, TBIL, GLB, and liver disease history was an important predictor of ATLI through LightGBM model, which could help clinicians in the early identification of ATLI.

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Publication Details

Journal
The Journal of Clinical Pharmacology
Published
2025-11-27
DOI
https://doi.org/10.1002/jcph.70131
Primary Topic
Drug-Induced Hepatotoxicity and Protection
Type
article
Field-Weighted Citation Impact
0.00

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article

Construction and Validation of a Predictive Model for the Risk of Anti‐Tuberculosis Drug‐Induced Liver Injury Based on Machine Learning Algorithms

Lihuan Lu, Jing-Ru C. Cheng, Hongqiu Pan, Shaowen Tang et al.
The Journal of Clinical Pharmacology
Drug-Induced Hepatotoxicity and Protection
article

Construction and Validation of a Predictive Model for the Risk of Anti‐Tuberculosis Drug‐Induced Liver Injury Based on Machine Learning Algorithms

Lihuan Lu, Jing-Ru C. Cheng, Hongqiu Pan, Shaowen Tang, Honggang Yi, Ruina Chen, Mei‐Ling Zhang, Xiaomin He
article en

Abstract

Anti-tuberculosis drug-induced liver injury (ATLI) is the most harmful to anti-tuberculosis (TB) treatment. This study aims to construct and validate a binary ATLI risk prediction model based on clinical data through seven machine learning algorithms (logistic regression, decision tree, support vector machine, random forest, gradient boosting decision tree, extreme gradient boosting, and light gradient boosting machine [LightGBM]). A retrospective cohort of 2356 TB patients followed between January 2017 and December 2024 was used to develop and evaluate the prediction model. Random undersampling was performed to address class imbalance problem. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and retained 27 of 31 original features. Seven ML algorithms were trained and the LightGBM model demonstrated optimal performance in testing set based on the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity (AUC = 0.789, sensitivity = 0.734, and specificity = 0.706). The model exhibited optimal simplicity and stability when incorporating the 8-feature combination comprising baseline high-density lipoprotein cholesterol (HDLC), γ-glutamyl transpeptidase (GGT), triglycerides, total cholesterol (TCHOL), uric acid, total bilirubin (TBIL), globulin (GLB), and liver disease history (AUC = 0.764, sensitivity = 0.758, and specificity = 0.610), and Shapely additive explanations analysis also revealed that these variables were the most influential contributors. The optimal model maintained robust predictive ability in the external validation cohort (AUC = 0.721, sensitivity = 0.828, and specificity = 0.604). This study determined that the combination of baseline HDLC, GGT, triglycerides, total cholesterol (TCHOL), uric acid, TBIL, GLB, and liver disease history was an important predictor of ATLI through LightGBM model, which could help clinicians in the early identification of ATLI.

The Journal of Clinical PharmacologyVol. 66(3)
Jiangsu University (CN), Taixing People's Hospital (CN), Affiliated Hospital of Jiangsu University (CN), Changshu No.1 People's Hospital (CN), Xian Yang Central Hospital (CN), Nanjing Medical University (CN)
National Natural Science Foundation of China
Openalex Percentile: Top 54%
Drug-Induced Hepatotoxicity and Protection
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