A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction
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.
Authors
- Kenza E. Benzeroual
- Mohammed Cherkaoui (ORCID: https://orcid.org/0000-0003-4619-2696)
- Nicolas Gallo (ORCID: https://orcid.org/0009-0004-7967-4266)
- Debarshi Ghosh (ORCID: https://orcid.org/0000-0001-9673-5762)
- Sharmila Anandasabapathy (ORCID: https://orcid.org/0000-0001-5876-831X)
- Sadhna Dhingra (ORCID: https://orcid.org/0000-0003-0436-033X)
- S Levine (ORCID: https://orcid.org/0000-0002-6139-7297)
- Valentine Cazaubon
- Stelian Camara Dit Pinto (ORCID: https://orcid.org/0000-0003-2155-1672)
- Jalal Cherkaoui
- John M. Vierling
- Gagan Sood
Institutions
- Long Island University (US)
- Baylor College of Medicine (US)
- Methodist Hospital (US)
- Dassault Systèmes (France) (FR)
- Institut National des Sciences Appliquées de Lyon (FR)
Publication Details
- Journal
- npj Digital Medicine
- Published
- 2024-11-27
- DOI
- https://doi.org/10.1038/s41746-024-01349-5
- Citations
- 3
- Primary Topic
- Drug-Induced Hepatotoxicity and Protection
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- Long Island University