Efficient analysis of drug interactions in liver injury: a retrospective study leveraging natural language processing and machine learning

Liver injury from drug-drug interactions (DDIs), notably with anti-tuberculosis drugs such as isoniazid, poses a significant safety concern. Electronic medical records contain comprehensive clinical information and have gained increasing attention as a potential resource for DDI detection. However, a substantial portion of adverse drug reaction (ADR) information is hidden in unstructured narrative text, which has yet to be efficiently harnessed, thereby introducing bias into the research. There is a significant need for an efficient framework for the DDI assessment. Using a Chinese natural language processing (NLP) model, we extracted 25,130 adverse drug reaction (ADR) records, dividing them into sets for training an automated normalization model. The trained models, in conjunction with liver function laboratory tests, were used to thoroughly and efficiently identify liver injury cases. Ultimately, we applied a case-control study design to detect DDI signals increasing isoniazid's liver injury risk. The Logistic Regression model demonstrated stable and superior performance in classification task. Based on laboratory criteria and NLP, we identified 128 liver injury cases among a cohort of 3,209 patients treated with isoniazid. Preliminary screening of 113 drug combinations with isoniazid highlighted 20 potential signal drugs, with antibacterials constituting 25%. Sensitivity analysis confirmed the robustness of signal drugs, especially in cardiac therapy and antibacterials. Our NLP and machine learning approach effectively identifies isoniazid-related DDIs that increase the risk of liver injury, identifying 20 signal drugs, mainly antibacterials. Further research is required to validate these DDI signals.