A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction

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

doi:10.1038/s41746-024-01349-5

A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction

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

Houston Methodist

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English (US)
Article number	340
Journal	npj Digital Medicine
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41746-024-01349-5
State	Published - Dec 2024

ASJC Scopus subject areas

Medicine (miscellaneous)
Health Informatics
Computer Science Applications
Health Information Management

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Camara Dit Pinto, S., Cherkaoui, J., Ghosh, D., Cazaubon, V., Benzeroual, K. E., Levine, S. M., Cherkaoui, M., Sood, G. K., Anandasabapathy, S., Dhingra, S., Vierling, J. M., & Gallo, N. R. (2024). A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction. npj Digital Medicine, 7(1), Article 340. https://doi.org/10.1038/s41746-024-01349-5

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title = "A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction",

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.",

author = "\{Camara Dit Pinto\}, Stelian and Jalal Cherkaoui and Debarshi Ghosh and Valentine Cazaubon and Benzeroual, \{Kenza E.\} and Levine, \{Steven M.\} and Mohammed Cherkaoui and Sood, \{Gagan K.\} and Sharmila Anandasabapathy and Sadhna Dhingra and Vierling, \{John M.\} and Gallo, \{Nicolas R.\}",

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AU - Camara Dit Pinto, Stelian

AU - Cherkaoui, Jalal

AU - Ghosh, Debarshi

AU - Cazaubon, Valentine

AU - Benzeroual, Kenza E.

AU - Levine, Steven M.

AU - Cherkaoui, Mohammed

AU - Sood, Gagan K.

AU - Anandasabapathy, Sharmila

AU - Dhingra, Sadhna

AU - Vierling, John M.

AU - Gallo, Nicolas R.

PY - 2024/12

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N2 - 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.

AB - 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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A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction

Abstract

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