Machine learning models based on adipocyte fatty acid-binding protein help predict the chronic and lethal outcomes of patients with drug-induced liver injury.

Purpose: Some patients with drug-induced liver injury (DILI) would progress into chronicity or lethal. Although adipocyte fatty acid-binding protein (AFABP) is essential in liver diseases, its role in DILI is unknown. We aimed to investigate their association and construct predictive models for chronic/lethal DILI using machine learning.

Methods: DILI patients (n = 331) were enrolled and categorized into recovery (n = 213), chronicity (n = 89), or death/liver transplantation (LT) group (n = 29) based on 6-month follow-up. ELISA and immunohistochemistry were used to determine serum and hepatic AFABP levels, respectively. Patients were randomly divided into training (70%) and validation (30%) cohorts. Machine learning models were constructed for chronic and death/LT outcomes based on serum AFABP. Furthermore, the performance of previous models and constructed models were evaluated for predicting death/LT outcome.

Results: The AFABP level was associated with the progression of DILI patients, whatever in serum or liver. The Extreme Gradient Boosting model presented the best predictive performance for chronic DILI, with the AUROC of 0.87 (95%CI = 0.82-0.91) in training cohort and AUROC of 0.90 (95%CI = 0.82-0.95) in validation cohort. The logistic regression model presented the best predictive performance for death/LT outcome, with the AUROC of 0.90 (95%CI = 0.85-0.94) in training cohort and AUROC of 0.92 (95%CI = 0.83-0.96) in validation cohort. Furthermore, it showed better predictive performance for death/LT outcome than previous models.

Conclusion: Serum AFABP level was associated with DILI progression, and machine learning models based on AFABP accurately predicted DILI outcomes, potentially assisting clinical management. Key messages What is already known on this topic: The chronic and lethal drug-induced liver injury (DILI) harms human health. Although adipocyte fatty acid-binding protein (AFABP) is essential in liver diseases, its role in DILI is unknown. We aimed to investigate their association and construct predictive models for chronic/lethal DILI using machine learning. What this study adds: The AFABP was associated with the progression of DILI patients, whatever in serum or liver. The Extreme Gradient Boosting model presented the best predictive performance for chronic DILI. The logistic regression model presented the best predictive performance for lethal DILI. Furthermore, it showed better predictive performance for lethal DILI than previous models. How this study might affect research, practice, or policy: We demonstrated that serum AFABP level was associated with the progression of DILI, and constructed accurate machine learning models to predict DILI outcomes based on serum AFABP, which could assist the clinical management of DILI patients.