Upstream eventNecrotic Tissue
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Mitochondrial complex inhibition leading to liver injury||adjacent||High||High|
|IKK complex inhibition leading to liver injury||adjacent||High||High|
Life Stage Applicability
Key Event Relationship Description
Logically when liver tissue is degraded, the liver will fail to execute its function. Again, this can be tissue type dependent(Krishna 2017)
Evidence Supporting this KER
Necrotic tissue is frequently observed in liver disease, e.g. a failing liver.
(Guicciardi et al. 2013): Apoptosis and necrosis in the liver.
(Luedde et al. 2014): Cell death in liver disease.
(Krishna 2017): Patterns of Necrosis in Liver disease.
(Malhi et al. 2006): Apoptosis and necrosis in the liver (including TNF signaling (NFkB and Caspase8) part)
Uncertainties and Inconsistencies
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Krishna, M., 2017. Patterns of Necrosis in Liver Disease. , 10(2), pp.53–56.
Guicciardi, M.E. et al., 2013. Apoptosis and Necrosis in the Liver. Comprehensive Physiology, 3(2), pp.977–1010. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3867948&tool=pmcentrez&rendertype=abstract.
Luedde, T., Kaplowitz, N. & Schwabe, R.F., 2014. Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance. Gastroenterology., 14(11), pp.871–882.
Malhi, H., Gores, G.J. & Lemasters, J.J., 2006. Apoptosis and necrosis in the liver: A tale of two deaths? Hepatology, 43(2 SUPPL. 1), pp.31–44.