The authors have designated this AOP as all rights reserved. Re-use in any form requires advanced permission from the authors.

AOP: 494


A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE.  More help

AhR activation leading to liver fibrosis

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
AhR and chronic liver diseases
The current version of the Developer's Handbook will be automatically populated into the Handbook Version field when a new AOP page is created.Authors have the option to switch to a newer (but not older) Handbook version any time thereafter. More help
Handbook Version v2.5

Graphical Representation

A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs. More help
Click to download graphical representation template Explore AOP in a Third Party Tool


The names and affiliations of the individual(s)/organisation(s) that created/developed the AOP. More help

Xavier Coumoul*, Min Ji Kim$, Karine Audouze*, Etienne Blanc*, Jean-Pascal de Bandt*

Institutions : Université Paris Cité*, Université Sorbonne Nord$ / Inserm T3S Umr-S 1124

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section.   More help
Cataia Ives   (email point of contact)


Users with write access to the AOP page.  Entries in this field are controlled by the Point of Contact. More help
  • Xavier COUMOUL
  • Min Ji Kim
  • Karine Audouze
  • Etienne Blanc
  • Cataia Ives


This field is used to identify coaches who supported the development of the AOP.Each coach selected must be a registered author. More help

OECD Information Table

Provides users with information concerning how actively the AOP page is being developed and whether it is part of the OECD Workplan and has been reviewed and/or endorsed. OECD Project: Assigned upon acceptance onto OECD workplan. This project ID is managed and updated (if needed) by the OECD. OECD Status: For AOPs included on the OECD workplan, ‘OECD status’ tracks the level of review/endorsement of the AOP . This designation is managed and updated by the OECD. Journal-format Article: The OECD is developing co-operation with Scientific Journals for the review and publication of AOPs, via the signature of a Memorandum of Understanding. When the scientific review of an AOP is conducted by these Journals, the journal review panel will review the content of the Wiki. In addition, the Journal may ask the AOP authors to develop a separate manuscript (i.e. Journal Format Article) using a format determined by the Journal for Journal publication. In that case, the journal review panel will be required to review both the Wiki content and the Journal Format Article. The Journal will publish the AOP reviewed through the Journal Format Article. OECD iLibrary published version: OECD iLibrary is the online library of the OECD. The version of the AOP that is published there has been endorsed by the OECD. The purpose of publication on iLibrary is to provide a stable version over time, i.e. the version which has been reviewed and revised based on the outcome of the review. AOPs are viewed as living documents and may continue to evolve on the AOP-Wiki after their OECD endorsement and publication.   More help
OECD Project # OECD Status Reviewer's Reports Journal-format Article OECD iLibrary Published Version
This AOP was last modified on May 26, 2024 20:39

Revision dates for related pages

Page Revision Date/Time
Activation, AhR February 28, 2024 05:12
Up Regulation, CYP1A1 September 16, 2017 10:15
Increase, Reactive oxygen species March 19, 2019 09:41
Cell injury/death July 15, 2022 09:46
Activation, Stellate cells November 10, 2019 05:25
Leukocyte recruitment/activation December 01, 2017 09:33
Increased, extracellular matrix deposition January 25, 2022 16:26
N/A, Liver fibrosis December 05, 2018 08:29
Increased, Liver Steatosis May 21, 2024 10:00
Activation, AhR leads to Up Regulation, CYP1A1 December 03, 2016 16:37
Up Regulation, CYP1A1 leads to Increase, ROS April 13, 2023 08:40
Activation, AhR leads to Increased, Liver Steatosis May 14, 2024 13:55
Increased, Liver Steatosis leads to Cell injury/death May 14, 2024 13:53
Cell injury/death leads to Activation, Stellate cells November 29, 2016 19:54
Cell injury/death leads to Leukocyte recruitment/activation April 13, 2023 08:44
Leukocyte recruitment/activation leads to Increased extracellular matrix deposition April 13, 2023 08:44
Activation, Stellate cells leads to Increased extracellular matrix deposition April 13, 2023 08:47
Increased extracellular matrix deposition leads to N/A, Liver fibrosis April 10, 2021 11:49
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) February 09, 2017 14:32


A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance. More help

Liver fibrosis, characterized by excessive accumulation of extracellular matrix proteins, represents a significant health burden worldwide. The Ah receptor (AhR), a ligand-activated transcription factor primarily known for its involvement in xenobiotic metabolism, has emerged as a key player in various physiological processes, including liver homeostasis and inflammation. Recent studies have implicated the AhR signaling pathway in the development and progression of liver fibrosis. This AOP provides a comprehensive overview of the molecular mechanisms underlying the association between AhR activation and liver fibrogenesis. AhR activation by endogenous ligands, such as tryptophan metabolites and environmental toxins, triggers a cascade of events leading to hepatic stellate cell activation, inflammation, and fibrogenesis. Understanding the intricate interplay between AhR and liver fibrosis offers novel insights into the pathogenesis of chronic liver diseases and highlights AhR as a potential therapeutic target for the management of liver fibrosis.

AOP Development Strategy


Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. More help

Understanding the biological link between Ah receptor (AhR) activation and liver fibrosis holds significant relevance due to its implications in the pathogenesis of various liver diseases. Liver fibrosis represents a common pathological process underlying the progression of chronic liver disorders, including hepatitis, alcoholic liver disease, and non-alcoholic fatty liver disease (NAFLD). Notably, NAFLD, characterized by hepatic steatosis, inflammation, and fibrosis, has become a global health concern, closely associated with obesity, metabolic syndrome, and insulin resistance. Given that AhR activation has been implicated in the regulation of lipid metabolism and inflammation, elucidating its role in liver fibrosis provides valuable insights into the molecular mechanisms driving NAFLD progression. Moreover, the interconnected nature of liver diseases underscores the importance of investigating AhR-mediated pathways as potential therapeutic targets for the management of liver fibrosis and its comorbidities, including hepatic steatosis. Therefore, establishing a biological link between AhR activation and liver fibrosis not only enhances our understanding of disease pathogenesis but also offers promising avenues for the development of targeted therapies for liver-related disorders.


Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components.  Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used). More help

We have been working for many years on chronic liver diseases and AhR. We had written a review on the subject and, following on from experimental work showing the links between AhR and fibrosis (two publications), we decided as part of the PARC project to take advantage of this expertise to publish this AOP. 

Summary of the AOP

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Molecular Initiating Events (MIE)
An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP. More help
Key Events (KE)
A measurable event within a specific biological level of organisation. More help
Adverse Outcomes (AO)
An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help
Type Event ID Title Short name
MIE 18 Activation, AhR Activation, AhR
KE 80 Up Regulation, CYP1A1 Up Regulation, CYP1A1
KE 1364 Increase, Reactive oxygen species Increase, ROS
KE 55 Cell injury/death Cell injury/death
KE 459 Increased, Liver Steatosis Increased, Liver Steatosis
KE 265 Activation, Stellate cells Activation, Stellate cells
KE 1494 Leukocyte recruitment/activation Leukocyte recruitment/activation
KE 1501 Increased, extracellular matrix deposition Increased extracellular matrix deposition
AO 344 N/A, Liver fibrosis N/A, Liver fibrosis

Relationships Between Two Key Events (Including MIEs and AOs)

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Network View

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Prototypical Stressors

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Life Stage Applicability

The life stage for which the AOP is known to be applicable. More help
Life stage Evidence
Adults Moderate

Taxonomic Applicability

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Sex Applicability

The sex for which the AOP is known to be applicable. More help

Overall Assessment of the AOP

Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). More help

Domain of Applicability

Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context. More help

Essentiality of the Key Events

The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs. More help

Evidence Assessment

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Known Modulating Factors

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Modulating Factor (MF) Influence or Outcome KER(s) involved

Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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