J Clin Invest 115(2): 209-218

Liver fibrosis

^{Liver Unit, Institut de Malalties Digestives i Metabòliques, Hospital Clinic, Institut d’Investigació Biomèdiques August Pi i Sunyer (IDIBAPS),Barcelona, Catalonia, Spain.}^{Department of Medicine, Columbia University, New York, New York, USA.}

Address correspondence to: David A. Brenner, Department of Medicine, Columbia University Medical Center, College of Physicians and Surgeons, 622 West 168th Street, PH 8E-105J, New York, New York 10032, USA. Phone: (212) 305-5838; Fax: (212) 305-8466; E-mail: ude.aibmuloc@6012bad.

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-β1, 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.

Abstract

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Acknowledgments

The authors’ work is supported by grants from the NIH, the Ministerio de Ciencia y Tecnología de España, and the Instituto de Investigación Carlos III (SAF2002-03696 and BFI2002-01202).

Due to space constraints, a number of important references could not be included in this article. References S1–S27 are available online with this article; doi:10.1172/JCI200524282DS1.

Acknowledgments

Footnotes

Nonstandard abbreviations used: CTLA, cytotoxic T lymphocyte antigen; HSC, hepatic stellate cell; NASH, nonalcoholic steatohepatitis; PBC, primary biliary cirrhosis; TIMP-1, tissue inhibitor of metalloproteinase type 1.

Conflict of interest: The authors have declared that no conflict of interest exists.

Footnotes

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