Mechanistic Modelling of Drug-Induced Liver Injury: Investigating the Role of Innate Immune Responses.

Published online

Journal Article

Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration. The representation of innate immune responses, detailed here, consolidates much of the available data on the innate immune response in DILI within a single framework and affords the opportunity to systematically investigate the contribution of the innate response to DILI.

Full Text

Duke Authors

Cited Authors

  • Shoda, LK; Battista, C; Siler, SQ; Pisetsky, DS; Watkins, PB; Howell, BA

Published Date

  • 2017

Published In

Volume / Issue

  • 11 /

Start / End Page

  • 1177625017696074 -

PubMed ID

  • 28615926

Pubmed Central ID

  • 28615926

International Standard Serial Number (ISSN)

  • 1177-6250

Digital Object Identifier (DOI)

  • 10.1177/1177625017696074

Language

  • eng

Conference Location

  • United States