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Key Event Title
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|Mitochondrial complex inhibition leading to liver injury||AdverseOutcome||Arthur Author (send email)||Under development: Not open for comment. Do not cite|
|IKK complex inhibition leading to liver injury||AdverseOutcome||Brendan Ferreri-Hanberry (send email)||Under development: Not open for comment. Do not cite|
|Inhibition of N-linked glycosylation leads to liver injury||AdverseOutcome||Arthur Author (send email)||Under development: Not open for comment. Do not cite|
Key Event Description
Hepatic Injury after apoptosis.(Landesmann, 2016)
Liver injury is the altered state of the liver wherein the normal homeostasis of all process in the liver are perturbed.
4 types of liver injury are distinguished in patients:
(= acute hepatitis)
Characteristics = elevation of serum transaminases (ALT+AST)
(= obstruction of the bile duct (bile cannot flow from liver to duodenum))
a) elevation in serum alkaline phosphatase (ALP) with normal or mild elevations in serum transaminases (ALT+AST)
b) elevated bilirubin levels
(= sarcoidosis, tuberculosis, liver abscess, metastatic malignancy)
a) elevation in serum alkaline phosphatase with normal or mild elevations (less than five times normal) in serum transaminases
b) no effects at bilirubin levels
(= autoimmune disease against liver components)
Characteristics = can present itself as hepatocellular when hepatocytes are target (= autoimmune hepatitis) or cholestatic when biliary ducts is the target (primary biliary cirrhosis)
Drug induced liver injury mostly manifest itself as hepatocellular injury, cholestasis or a mixture of both. In a mixture hepatitis the amount of hepatocellular and cholestatic features vary per case.
Biopsy results with mixed hepatitis is a combination of:
Hepatocellular = liver cell necrosis, inflammation
Choleostatic = bile stasis, portal inflammation, injury of bile ducts
Patient with any kind of mixed hepatitis demonstrates the following symptoms:
First symptoms = Fatigue, anorexia and nausea
Later symptoms = jaundice (=skin and eye white become yellows/greenish) dark urine and pruritus (= sensitization of itch)
How It Is Measured or Detected
Indicators of liver injury include: Levels of: ALT, AST, ALP, bilirubin, GGT, NTP, Ceruloplasmin, AFP
(Guicciardi et al. 2013)
Test in patients or in vivo(Gowda et al. 2009) (Musana et al. 2004):
· Biochemistry assays
· Levels of: ALT, AST, ALP, bilirubin, GGT, NTP, Ceruloplasmin, AFP,
· Imaging scans
Domain of Applicability
Regulatory Significance of the Adverse Outcome
Landesmann, B. (2016). Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis, (2).
Guicciardi ME, Malhi H, Mott JL, Gores GJ (2013) Apoptosis and Necrosis in the Liver Maria. Compr Physiol 3:977–1010 . doi: 10.1002/cphy.c120020.Apoptosis
Musana, K.A., Yale, S.H. & Abdulkarim, A.S., 2004. Tests of liver injury. Clin Med Res, 2(2), pp.129–131.
Gowda, S. et al., 2009. A review on laboratory liver function tests. The Pan African medical journal, 3(November), p.17. Available at: http://www.ncbi.nlm.nih.gov/pubmed/21532726%5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC2984286.