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Chronic Liver Failure pp 91–107Cite as

Fibrosis as a Major Mechanism of Chronic Liver Disease

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Part of the book series: Clinical Gastroenterology ((CG))

Abstract

Hepatic fibrosis and even cirrhosis have emerged as treatable and reversible consequences of chronic liver disease. With dramatic advances in understanding the cellular and molecular basis of fibrosis, there is increasing enthusiasm for new treatments that attack hepatic fibrosis directly. Basic research has focused on the hepatic stellate cell, which undergoes activation into a proliferative and fibrogenic myofibroblast-like cell during liver injury and is an important source of extracellular matrix in the liver. In addition, other fibrogenic populations, for example, portal fibroblasts, fibrocytes, and possibly bone-marrow-derived cells, as well as cells derived from epithelial–mesenchymal transition may be additional sources of extracellular matrix. Stimuli driving stellate cell activation include hepatocellular necrosis, apoptosis, and soluble growth factors. A cascade of signaling pathways and transcriptional events in stellate cells underlies the fibrogenic response to liver injury, with each step in the cascade representing a potential target for antifibrotic therapy. A key clinical challenge is to establish noninvasive means of assessing fibrosis stage and progression using serum tests, imaging, functional tests, and/or elastography. Given the slow course of disease progression, endpoints of antifibrotic clinical trials need to be established that provide evidence of benefit within a short interval. With continued progress, antifibrotic therapies will soon be a reality in treating chronic fibrosing liver disease.

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Authors and Affiliations

  1. Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, USA

    Scott L. Friedman

  2. Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Lars P. Bechmann

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  1. Lars P. Bechmann
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  2. Scott L. Friedman
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Correspondence to Scott L. Friedman .

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Editors and Affiliations

  1. Liver Unit, Hospital Clinic, University of Barcelona, Villarroel 170, Barcelona, 08036, Spain

    Pere Ginès

  2. College of Medicine, Division of Gastroenterology and Hepatol, Mayo Clinic, 200 First St. S.W, Rochester, 55905, Minnesota, USA

    Patrick S. Kamath

  3. Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, 08036, Spain

    Vicente Arroyo

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Bechmann, L.P., Friedman, S.L. (2011). Fibrosis as a Major Mechanism of Chronic Liver Disease. In: Ginès, P., Kamath, P., Arroyo, V. (eds) Chronic Liver Failure. Clinical Gastroenterology. Humana Press. https://doi.org/10.1007/978-1-60761-866-9_5

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