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Event: 1549

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Liver Injury

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Liver Injury
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Organ

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE. Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
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

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

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:

Hepatocellular

(= acute hepatitis)

Characteristics = elevation of serum transaminases (ALT+AST)

Choleostatic

(= obstruction of the bile duct (bile cannot flow from liver to duodenum))

Characteristics =

a) elevation in serum alkaline phosphatase (ALP) with normal or mild elevations in serum transaminases (ALT+AST)

b) elevated bilirubin levels

Infiltrative

(= sarcoidosis, tuberculosis, liver abscess, metastatic malignancy)

Characteristics =

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

(= 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

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

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

· Ultrasound

· CT

· MRI

· Biopsy

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Regulatory Significance of the Adverse Outcome

An AO is a specialised KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

References

List of the literature that was cited for this KE description. More help

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.