Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy

Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy...

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Veröffentlicht in:Archives of toxicology 2024-09, Vol.98 (9), p.3049-3061
Hauptverfasser: Ma, Hongying, Huang, Sihui, Li, Fengxin, Pang, Zicheng, Luo, Jian, Sun, Danfeng, Liu, Junsong, Chen, Zhuoming, Qu, Jian, Qu, Qiang
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container_end_page 3061
container_issue 9
container_start_page 3049
container_title Archives of toxicology
container_volume 98
creator Ma, Hongying
Huang, Sihui
Li, Fengxin
Pang, Zicheng
Luo, Jian
Sun, Danfeng
Liu, Junsong
Chen, Zhuoming
Qu, Jian
Qu, Qiang
description Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using “H2O” autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.
doi_str_mv 10.1007/s00204-024-03803-5
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subjects Abnormalities
Adolescent
Adult
Aged
Algorithms
Anticonvulsants - adverse effects
automation
Bilirubin
Biomedical and Life Sciences
Biomedicine
Chemical and Drug Induced Liver Injury - etiology
chi-square distribution
Chi-square test
Child
Child, Preschool
data collection
Datasets
Environmental Health
Epilepsy
Epilepsy - drug therapy
Female
Hepatotoxicity
Humans
In Silico
Learning algorithms
leukocyte count
Machine Learning
Male
Middle Aged
Occupational Medicine/Industrial Medicine
oral administration
Parameters
Pharmacology/Toxicology
Pharmacovigilance
Prediction models
Predictions
Regression analysis
risk
t-test
Transaminase
Transaminases
Transaminases - blood
Valproic Acid
Young Adult
title Development and validation of an automatic machine learning model to predict abnormal increase of transaminase in valproic acid-treated epilepsy
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