API

Event: 1549

Key Event Title

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Liver Injury

Short name

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Liver Injury

Biological Context

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Level of Biological Organization
Organ


Organ term

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Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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Stressors

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Taxonomic Applicability

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Life Stages

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Sex Applicability

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Key Event Description

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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

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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

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Regulatory Significance of the Adverse Outcome

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References

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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.