Multiscale Modeling of Drug-Induced Liver Injury From Organ to Lobule

Authors

Alon Malka-Markovitz
Stelian Camara Dit Pinto
Mohammed Cherkaoui
Steven M Levine
Sharmila Anandasabapathy
Gagan K Sood
Sadhna Dhingra
Gao Yujia
John M Vierling
Nicolas R Gallo

Publication Date

6-23-2025

Journal

npj Digital Medicine

DOI

10.1038/s41746-025-01736-6

PMID

40550856

PMCID

PMC12185720

PubMedCentral® Posted Date

7-23-2025

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Computational models, Translational research, Computational science

Abstract

Drug-induced liver injury poses significant challenges in drug development and in clinical care. This study builds on prior work developing a Human Liver Virtual Twin by creating a Multiscale Computational Fluid Dynamics framework that integrates patient-specific anatomical data to predict acetaminophen-induced liver injury as a demonstration of its capability. The model bridges vascular, lobular, and cellular scales to simulate dynamic blood flow, drug transport, and injury mechanisms that accurately reflect clinically observed spatial heterogeneity. Results demonstrate accurate blood flow dynamics, predictions of hepatocellular damage, and a scalable framework for studying spatial heterogeneity applicable to other hepatic pathologies. This work establishes the foundational principles for a whole-organ virtual liver simulation methodology, potentially becoming a powerful tool to guide safety in therapeutic development and clinical treatment strategies, ultimately reducing reliance translation from animal models for preclinical drug testing.