Predicting Antituberculosis Drug–Induced Liver Injury Using an Interpretable Machine Learning Method: Model Development and Validation Study

Zhong, Tao; Zhuang, Zian; Dong, Xiaoli; Wong, Ka Hing; Wong, Wing Tak; Wang, Jian; He, Daihai; Liu, Shengyuan

BACKGROUND: Tuberculosis (TB) is a pandemic, being one of the top 10 causes of death and the main cause of death from a single source of infection. Drug-induced liver injury (DILI) is the most common and serious side effect during the treatment of TB. OBJECTIVE: We aim to predict the status of liver injury in patients with TB at the clinical treatment stage. METHODS: We designed an interpretable prediction model based on the XGBoost algorithm and identified the most robust and meaningful predictors of the risk of TB-DILI on the basis of clinical data extracted from the Hospital Information System of Shenzhen Nanshan Center for Chronic Disease Control from 2014 to 2019. RESULTS: In total, 757 patients were included, and 287 (38%) had developed TB-DILI. Based on values of relative importance and area under the receiver operating characteristic curve, machine learning tools selected patients’ most recent alanine transaminase levels, average rate of change of patients’ last 2 measures of alanine transaminase levels, cumulative dose of pyrazinamide, and cumulative dose of ethambutol as the best predictors for assessing the risk of TB-DILI. In the validation data set, the model had a precision of 90%, recall of 74%, classification accuracy of 76%, and balanced error rate of 77% in predicting cases of TB-DILI. The area under the receiver operating characteristic curve score upon 10-fold cross-validation was 0.912 (95% CI 0.890-0.935). In addition, the model provided warnings of high risk for patients in advance of DILI onset for a median of 15 (IQR 7.3-27.5) days. CONCLUSIONS: Our model shows high accuracy and interpretability in predicting cases of TB-DILI, which can provide useful information to clinicians to adjust the medication regimen and avoid more serious liver injury in patients.