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Cited by 71Liver physiology and pathologyLiver Disease Diagnosis and TreatmentDrug-Induced Hepatotoxicity and Protection

An update on animal models of liver fibrosis

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Wu, ShuTing, Wang, XinXin, Xing, WenBo, Li, FenYao, Liang, Ming, Li, KeShen, He, Yan, Wang, JianMing·2023·Frontiers in Medicine
DOI 10.3389/fmed.2023.1160053PMC PMC10076546
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Abstract

The development of liver fibrosis primarily determines quality of life as well as prognosis. Animal models are often used to model and understand the underlying mechanisms of human disease. Although organoids can be used to simulate organ development and disease, the technology still faces significant challenges. Therefore animal models are still irreplaceable at this stage. Currently, in vivo models of liver fibrosis can be classified into five categories based on etiology: chemical, dietary, surgical, transgenic, and immune. There is a wide variety of animal models of liver fibrosis with varying efficacy, which have different implications for proper understanding of the disease and effective screening of therapeutic agents. There is no high-quality literature recommending the most appropriate animal models. In this paper, we will describe the progress of commonly used animal models of liver fibrosis in terms of their development mechanisms, applications, advantages and disadvantages, and recommend appropriate animal models for different research purposes.

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  • The CCl4 model has disadvantages including high individual variation and systemic toxicity.

    “Disadvantages thereof include high individual variation and system toxicity of the drug due to its extensive tissue actions [68, 69].”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [69]

    The CCl4-induced liver fibrosis model section (page not available) says CCl4 is highly toxic, but does not describe systemic toxicity due to extensive tissue actions. It calls the model reproducible, rather than identifying high individual variation as a disadvantage. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The CCl4 model resembles numerous characteristics of alcoholic cirrhosis in humans, including progressive fibrosis.

    “The model resembles numerous characteristics of alcoholic cirrhosis (AC) in humans, including progressive fibrosis.”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [69]

    The CCl4-induced liver fibrosis model section (page unavailable) describes severe fibrosis, and Discussions and prospect says the model resembles human liver fibrosis in some morphological and pathophysiological respects. But the comparison with human alcoholic liver disease appears in Combine induction methods > Chemical + chemical (page unavailable) for a model using CCl4 plus ethanol, not CCl4 alone. The copy does not establish that the CCl4-only model resembles numerous characteristics of human alcoholic cirrhosis. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • CCl4 administration twice a week for 6-8 weeks induces oxidative stress and activates HSCs.

    “Subcutaneous or intraperitoneal administration twice a week for 6–8 weeks induces oxidative stress and activates HSCs using the CCl₄ induction schedule.”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [69]

    The CCl₄-induced liver fibrosis model section says CCl₄ causes oxidative stress, and the Introduction’s Figure 1 describes HSC activation in chemical-induction models. But the paper gives the usual CCl₄ schedule as intraperitoneal injection 2–3 times weekly for 4–6 weeks; it does not support the claimed subcutaneous route or 6–8-week schedule. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The BDL model is widely employed to study cholestatic cirrhosis, including primary biliary cholangitis.

    “The model is widely employed to study cholestatic cirrhosis, including primary biliary cholangitis [69].”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [69]

    The Surgical induction methods section calls BDL the most widely used experimental model for cholestasis and says it can induce cirrhosis in rats. It describes the model as producing obstructive, extrahepatic cholestasis, but does not identify primary biliary cholangitis as a condition it is used to study. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The BDL model induces cholestasis, inflammation, and hepatic fibrosis within 2-3 weeks.

    “The BDL model, with surgical occlusion of the common bile duct, immediately induces cholestasis, inflammation, and hepatic fibrosis within 2–3 weeks.”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [69]

    The Surgical induction methods section says BDL obstructs the common bile duct and produces cholestasis, inflammation, and fibrosis. It reports fibrosis developing by days 10 and 20 in mice, which supports the 2–3-week timeframe for mice, but does not establish that timeframe generally or that inflammation and fibrosis arise immediately. No page number is available in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Wu, S., Wang, X., Xing, W., Li, F., Liang, M., Li, K., He, Y., & Wang, J.
Affiliations
Wuhan University of Science and Technology (CN)
Corresponding author
  • He, Yan
  • Wang, JianMing
ORCID
Venue
Frontiers in Medicine
Publisher
Frontiers Media SA
Published
2023-03-23
Volume
10
Pages
1160053-1160053
ISSN
2296-858X (ISSN-L)
DOI
10.3389/fmed.2023.1160053
PMC
PMC10076546
OpenAlex
W4360618851
Cited by
71
References
8
Citations by year
2026: 16 · 2025: 29 · 2024: 21 · 2023: 5
FWCI
3.10
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Wuhan University of Science and Technology
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
liver fibrosis, animal models, in vivo models, surgical models, transgenic models, organoids, therapeutic screening

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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