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Cited by 1,237Liver physiology and pathologyLiver Disease Diagnosis and TreatmentLiver Diseases and Immunity

Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives

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Roehlen, Natascha, Crouchet, Emilie, Baumert, Thomas F.·2020·Cells
DOI 10.3390/cells9040875PMC PMC7226751
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Abstract

Liver fibrosis due to viral or metabolic chronic liver diseases is a major challenge of global health. Correlating with liver disease progression, fibrosis is a key factor for liver disease outcome and risk of hepatocellular carcinoma (HCC). Despite different mechanism of primary liver injury and disease-specific cell responses, the progression of fibrotic liver disease follows shared patterns across the main liver disease etiologies. Scientific discoveries within the last decade have transformed the understanding of the mechanisms of liver fibrosis. Removal or elimination of the causative agent such as control or cure of viral infection has shown that liver fibrosis is reversible. However, reversal often occurs too slowly or too infrequent to avoid life-threatening complications particularly in advanced fibrosis. Thus, there is a huge unmet medical need for anti-fibrotic therapies to prevent liver disease progression and HCC development. However, while many anti-fibrotic candidate agents have shown robust effects in experimental animal models, their anti-fibrotic effects in clinical trials have been limited or absent. Thus, no approved therapy exists for liver fibrosis. In this review we summarize cellular drivers and molecular mechanisms of fibrogenesis in chronic liver diseases and discuss their impact for the development of urgently needed anti-fibrotic therapies.

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  • Reversion of fibrosis is a gradual process that typically takes years to achieve.

    “Reversion of fibrosis, however, is a gradual process that typically takes years to achieve [7, 8].”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [8]

    Section 4, “Resolution of Liver Fibrosis” (page unavailable), says spontaneous resolution after removal or treatment of the inflammatory trigger occurs slowly. It does not say that reversion typically takes years, so the claimed timeframe is unsupported. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Early-stage cirrhosis can be reversible if the etiologic factor is addressed early through antiviral therapy or extended alcohol abstinence.

    “Cirrhosis, if in early stages, can be reversible if the etiologic factor (e.g., viral hepatitis or alcohol use) is addressed early through interventions such as antiviral therapy or extended alcohol abstinence.”

    From From signaling pathways to clinical trials: mesenchymal stem cells as multimodal regenerative architects in liver cirrhosis therapy (2025) · cites this paper as [8]

    Section 4, “Resolution of Liver Fibrosis” (page not provided), reports that removing the cause of chronic HBV or HCV infection can reverse fibrosis, including advanced fibrosis, though reversal is not universal. Section 3.3 identifies alcohol as a cause of fibrosis, but the paper does not specifically say that extended alcohol abstinence reverses cirrhosis or establish the claim’s early-intervention condition. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • During liver fibrosis, extracellular matrix deposition causes a progressive increase in tissue stiffness.

    “In parallel, the extracellular matrix (ECM) deposition causes a progressive increase of stiffness [1, 2].”

    From Mechanical stiffness orchestrates distinct regulation of <scp>MRTFs</scp> and <scp>YAP</scp> / <scp>TAZ</scp> transcriptional cofactors in hepatocytes (2026) · cites this paper as [2]

    The Introduction describes progressive ECM accumulation during liver fibrosis. Section 2.2 links ECM remodeling to changes in matrix stiffness, and Section 4.2 says collagen crosslinking contributes to stiffness. The paper does not explicitly establish that tissue stiffness increases progressively as ECM is deposited. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Roehlen, N., Crouchet, E., & Baumert, T. F.
Affiliations
  • Institute for Translational Medicine and Liver Disease (FR)
  • Université de Strasbourg, 67000 Strasbourg, France
  • Hôpitaux Universitaires de Strasbourg (FR)
Corresponding author
Baumert, Thomas F.
ORCID
Baumert, Thomas F.
Venue
Cells
Publisher
MDPI AG
Published
2020-04-03
Volume
9
Issue
4
Pages
875
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells9040875
PMC
PMC7226751
OpenAlex
W3014599953
Cited by
1,237
References
49
Citations by year
2026: 180 · 2025: 262 · 2024: 269 · 2023: 232 · 2022: 192 · 2021: 84 · 2020: 15 · 2019: 1 · 2018: 1
FWCI
17.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • European Union (ERC-AdG-2014-HEPCIR #671231, EU H2020-HEPCAR #667273, ERC PoC-HEPCAN #862551)
  • ARC, Paris and Institut Hospitalo-Universitaire, Strasbourg (IHUARC IHU201301187, IHUC201901299)
  • foundation of the University of Strasbourg (HEPKIN)
  • Agence National de Recherches sur le Sida et les Hépatites Virales (ANRS) (ANRS 2017/1633)
  • US National Institute of Health (R01CA233794, NCI 1R21CA209940-01A1)
  • Deutsche Forschungsgemeinschaft (RO 5983/1-1)
  • French National Research Agency (PLAN CANCER 2014-2019 HCCMICTAR, LABEX ANR-10-LABX-0028-HEPSYS)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
Keywords
liver fibrosis, chronic liver disease, antifibrotic therapy, hepatocellular carcinoma, viral hepatitis, metabolic liver disease, fibrosis reversibility
MeSH terms
Gastrointestinal Microbiome, Animals, Humans, Liver Cirrhosis, Models, Biological, Signal Transduction, Apoptosis, Oxidative Stress

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