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Event: 1395

Key Event Title

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

Liver Cancer

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 Cancer

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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

Organ term
liver

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
Cyp2E1 Activation Leading to Liver Cancer	AdverseOutcome	Francina Webster (send email)	Open for citation & comment	WPHA/WNT Endorsed

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

Term	Scientific Term	Evidence	Link
rodents	rodents	High	NCBI

Life Stages

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

Life stage	Evidence
All life stages	High

Sex Applicability

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

Term	Evidence
Mixed	High

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

Liver cancer is among the most common forms of cancer and the second leading cause of cancer death. It is more prevalent in males than females; however, prevalence has been increasing in both genders over the last two decades (Ellison, L.F., Wilkins, K. 2012). Hepatocellular carcinoma (HCC) is a primary cancer of the hepatocytes that is typically a progression from the benign hepatocellular adenoma (HCA). The most common risk factor for developing hepatocellular carcinoma is chronic liver injury and inflammation (caused by persistent infection, fatty liver disease, or chemical exposure). This disease is almost always lethal in the absence of extreme intervention measures (e.g., surgery, liver transplant).

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

In animal models, the presence of HCA and HCC are measured histologically following the standard two-year rodent bioassay, which is conducted according to OECD Test Guideline 451 (OECD 2009).
In humans, liver cancer is detected by abdominal CT scan followed by biopsy and pathological examination. Symptoms of liver cancer include: jaundice, abdominal pain, nausea, and liver dysfunction. Liver cancer is more common in patients with risk factors that include: viral hepatitis, non-viral hepatitis, chronic alcoholism, obesity leading to steatohepatitis, cirrhosis, and liver fluke infection (Bonder and Afdhal 2012, Paradis 2013, Venkatesh, et al. 2014).

Domain of Applicability

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

Hepatocellular carcinoma occurs in many vertebrate species including birds, fish, and mammals such as humans.

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

Any cancer endpoint is considered to be adverse from a regulatory perspective. Substances causing cancer are regulated such that the general population is not exposed to levels that exceed the carcinogenic dose. The standard assay for carcinogens is the two-year rodent bioassay, which is conducted by the National Toxicology Program in the U.S.A. (https://ntp.niehs.nih.gov/). The International Agency on Research on Cancer (IARC; https://www.iarc.fr/) categorizes substances based on available evidence pointing to their ability to cause cancer in humans and/or animals.

References

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

Bonder, A., Afdhal, N., 2012. Evaluation of liver lesions. Clin. Liver Dis. 16, 271-283.

Ellison, L.F., Wilkins, K., 2012. Canadian Trends in Cancer Prevalence. Health Reports 23.

OECD, 2009. OECD Guideline for the Testing of Chemicals: Carcinogenicity Studies (Test Guideline 451).

Paradis, V., 2013. Histopathology of hepatocellular carcinoma. Recent Results Cancer Res. 190, 21-32.

Venkatesh, S.K., Chandan, V., Roberts, L.R., 2014. Liver masses: a clinical, radiologic, and pathologic perspective. Clin. Gastroenterol. Hepatol. 12, 1414-1429.