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Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro
11:06

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro

Published on: January 31, 2022

Mechanisms of drug-induced liver disease

Basuki K Gunawan1, Neil Kaplowitz

  • 1Research Center for Liver Disease, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, HMR 101, Los Angeles, CA 90033, USA.

Clinics in Liver Disease
|August 29, 2007
PubMed

Insights

Drug-induced liver injury begins with liver cell stress and death, leading to immune system activation. Individual susceptibility varies due to genetics and environmental factors influencing these responses.

Area of Science:

  • Toxicology
  • Immunology
  • Hepatology

Background:

  • Drug-induced liver injury (DILI) is a significant clinical concern.
  • DILI pathogenesis involves hepatocyte stress, cell death, and immune system activation.
  • Individual susceptibility to DILI varies widely.

Purpose of the Study:

  • To elucidate the sequential events in drug-induced liver injury.
  • To explore the role of innate immunity in DILI outcomes.
  • To identify factors contributing to differential susceptibility to DILI.

Main Methods:

  • Review of existing literature on DILI mechanisms.
  • Analysis of cellular stress and death pathways in response to drugs.
  • Examination of innate immune system components in DILI.

Main Results:

  • Hepatocyte stress and cell death are initial events in DILI, triggered by drugs or metabolites.
  • Innate immune system recruitment follows, with its inflammatory/anti-inflammatory balance dictating injury outcome.
  • Genetic and environmental factors influence individual responses to cellular stress and immune activation.

Conclusions:

  • DILI is a complex process involving initial cellular damage followed by immune responses.
  • The interplay of inflammation and anti-inflammation within the innate immune system is critical for DILI progression.
  • Variations in genetic makeup and environmental exposures underlie individual differences in DILI susceptibility.

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