A Virtual Scalable Model of the Hepatic Lobule for Acetaminophen Hepatotoxicity Prediction

Authors

Stelian Camara Dit Pinto
Jalal Cherkaoui
Debarshi Ghosh
Valentine Cazaubon
Kenza E Benzeroual
Steven M Levine
Mohammed Cherkaoui
Gagan K Sood
Sharmila Anandasabapathy
Sadhna Dhingra
John M Vierling
Nicolas R Gallo

Publication Date

11-28-2024

Journal

npj Digital Medicine

DOI

10.1038/s41746-024-01349-5

PMID

39604584

PMCID

PMC11603025

PubMedCentral® Posted Date

11-28-2024

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

no

Abstract

Addressing drug-induced liver injury is crucial in drug development, often causing Phase III trial failures and market withdrawals. Traditional animal models fail to predict human liver toxicity accurately. Virtual twins of human organs present a promising solution. We introduce the Virtual Hepatic Lobule, a foundational element of the Living Liver, a multi-scale liver virtual twin. This model integrates blood flow dynamics and an acetaminophen-induced injury model to predict hepatocyte injury patterns specific to patients. By incorporating metabolic zonation, our predictions align with clinical zonal hepatotoxicity observations. This methodology advances the development of a human liver virtual twin, aiding in the prediction and validation of drug-induced liver injuries.

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