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Event: 2407

Key Event Title

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

Increase, Cirrhosis

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
Increase, Cirrhosis
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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
GR disruption leading to MASLD via IR-associated mitochondrial dysfunction AdverseOutcome You Song (send email) Under development: Not open for comment. Do not cite Under Development
GR disruption leading to MASLD via VLDL-associated mitochondrial dysfunction AdverseOutcome You Song (send email) Under development: Not open for comment. Do not cite Under Development
GR disruption leading to MASLD via lipogenesis-associated mitochondrial dysfunction AdverseOutcome You Song (send email) Under development: Not open for comment. Do not cite Under Development
GR disruption leading to MASLD via IR-associated ER stress AdverseOutcome You Song (send email) Under development: Not open for comment. Do not cite Under Development
GR disruption leading to MASLD via VLDL-associated ER stress AdverseOutcome You Song (send email) Under development: Not open for comment. Do not cite Under Development
GR disruption leading to MASLD via lipogenesis-associated ER stress AdverseOutcome You Song (send email) Under development: Not open for comment. Do not cite Under Development

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
Homo sapiens Homo sapiens NCBI
mouse Mus musculus NCBI
rat Rattus norvegicus NCBI
mammals mammals NCBI

Life Stages

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

Sex Applicability

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

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

Cirrhosis represents the end-stage consequence of chronic liver injury and sustained fibrogenesis. It is characterized by:

  • Extensive deposition of extracellular matrix (primarily type I collagen)

  • Bridging fibrosis connecting portal and central regions

  • Formation of regenerative nodules

  • Distortion of normal hepatic architecture

  • Altered vascular structure and portal hypertension

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

1. Histopathology (Gold Standard)

  • Masson's trichrome staining

  • Sirius Red staining for collagen deposition

  • Assessment of:

    • Bridging fibrosis

    • Nodular regeneration

    • Architectural distortion

Common scoring systems:

  • METAVIR (F4 stage indicates cirrhosis)

  • Ishak fibrosis score

  • SAF scoring system

2. Imaging (Clinical Context)

  • Transient elastography (FibroScan)

  • Magnetic resonance elastography

  • Ultrasound imaging (nodular surface, splenomegaly)

Imaging provides non-invasive assessment but histology confirms diagnosis.

3. Serum Biomarkers (Supportive)

  • Decreased albumin

  • Elevated bilirubin

  • Prolonged prothrombin time

  • Fibrosis biomarkers (e.g., hyaluronic acid, procollagen peptides)

These support functional impairment but do not independently confirm cirrhosis.

Domain of Applicability

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

Cirrhosis is a clinically recognized end-stage liver disease in humans and is reproducible in mammalian models of chronic hepatic injury. The mechanisms of fibrosis progression and architectural remodeling are highly conserved in mammals.

This KE is most applicable under:

  • Chronic exposure conditions

  • Sustained inflammatory and fibrogenic signaling

  • Adult or metabolically mature organisms

The biological plausibility is strong due to well-established fibrogenic pathways (e.g., TGF-β–mediated stellate cell activation) and consistent cross-species pathology.

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

An increase in cirrhosis represents:

  • A severe, adverse organ-level outcome

  • Largely irreversible structural liver damage

  • A major determinant of liver-related morbidity and mortality

From a regulatory perspective, cirrhosis constitutes a high-concern adverse outcome suitable for:

  • Chronic toxicity hazard identification

  • Chemical prioritization

  • Risk assessment frameworks

Because cirrhosis reflects irreversible architectural and functional liver impairment, it anchors the most severe end of MASLD progression within the AOP network.

References

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