Cited by 4,958Liver physiology and pathologyLiver Disease Diagnosis and TreatmentLiver Disease and Transplantation

Liver fibrosis

Open access
Bataller, Ramón, Brenner, David A.·2005·Journal of Clinical Investigation

Abstract

Liver fibrosis is the excessive accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines such as TGF-beta1, angiotensin II, and leptin. Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs. Emerging antifibrotic therapies are aimed at inhibiting the accumulation of fibrogenic cells and/or preventing the deposition of extracellular matrix proteins. Although many therapeutic interventions are effective in experimental models of liver fibrosis, their efficacy and safety in humans is unknown. This review summarizes recent progress in the study of the pathogenesis and diagnosis of liver fibrosis and discusses current antifibrotic strategies.

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  • HSCs have fibrosis-independent roles through RSPO3, regulating critical parameters that affect CLD progression and outcomes, including metabolic hepatocyte functions, liver regeneration and hepatocyte death.

    “The current study amends this fibrocentric concept by demonstrating fibrosis-independent roles for HSCs through RSPO3, regulating critical parameters that affect CLD progression and outcomes, including metabolic hepatocyte functions, liver regeneration and hepatocyte death2,49,50.”
  • In more advanced disease stages, the ECM can replace functional liver parenchyma and thereby contribute to the development of liver cirrhosis, which is characterized by bridging fibrosis, regenerative nodules, and the loss of liver function.

    “In more advanced disease stages, the ECM can replace functional liver parenchyma and thereby contribute to the development of liver cirrhosis, which is characterized by bridging fibrosis, regenerative nodules, and the loss of liver function [230].”
  • TGF-β and PDGF are prototype cytokines responsible for activation of hepatic stellate cells during liver injury.

    “Two of the prototype cytokines responsible for the activation of HSCs during liver injury are the transforming growth factor-β (TGF-β) and the platelet-derived growth factor (PDGF).[3]”

    From Nuclear receptors in liver fibrosis (2021) · cites this paper as [3]

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Research works printed but not linked: 1

  1. Ludwig, J., Viggiano, T.R., McGill, D.B., and Oh, B.J. 1980. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin. Proc. 55:434-438.

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Authors
Bataller, R., & Brenner, D. A.
Affiliations
Columbia University (US)
Corresponding author
Brenner, David A.
Venue
Journal of Clinical Investigation
Published
2005-02-01
Volume
115
Issue
2
Pages
209-218
ISSN
0021-9738 (ISSN-L)
OpenAlex
W4255712601
Cited by
4,958
References
136
Citations by year
2026: 177 · 2025: 236 · 2024: 285 · 2023: 289 · 2022: 307 · 2021: 321 · 2020: 294 · 2019: 275 · 2018: 284 · 2017: 295 · 2016: 281 · 2015: 307 · 2014: 229 · 2013: 224 · 2012: 222
FWCI
17.47
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministerio de Ciencia y Tecnología
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
Keywords
liver fibrosis, extracellular matrix accumulation, collagen deposition, chronic liver disease, liver cirrhosis, hepatic stellate cells, portal fibroblasts, myofibroblasts, TGF-β1, angiotensin II, leptin, fibrogenic cytokines, antifibrotic agents, fibrosis pathogenesis, fibrosis diagnosis, liver transplantation
MeSH terms
Angiotensin II, Animals, Humans, Hypertension, Portal, Liver Cirrhosis, Transforming Growth Factor beta, Liver Failure, Leptin

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