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Pathogenesis of hepatic fibrosis

Scott L Friedman, MD
Section Editor
Bruce A Runyon, MD
Deputy Editor
Kristen M Robson, MD, MBA, FACG


Fibrosis is a wound healing response in which damaged regions are encapsulated by an extracellular matrix or scar. It develops in almost all patients with chronic liver injury at variable rates depending in part upon the cause of liver disease and host factors [1-4]. In contrast, for unclear reasons, patients with self-limited injury (such as fulminant hepatitis) do not develop scarring despite an abundance of fibrogenic stimuli, unless they go on to develop chronic injury.

The composition of the hepatic scar is similar regardless of the cause of injury. Furthermore, hepatic fibrosis represents a paradigm for wound healing in other tissues, including skin, lung, and kidney, since it involves many of the same cell types and mediators.

Fibrosis occurs earliest in regions where injury is most severe, particularly in chronic inflammatory liver disease due to alcohol or viral infection. As an example, pericentral injury is a hallmark of alcoholic hepatitis; the development of pericentral fibrosis (also known as sclerosing hyaline necrosis or perivenular fibrosis) is an early marker of likely progression to panlobular cirrhosis [5].

The development of fibrosis usually requires several months to years of ongoing injury. Two exceptions in adults are veno-occlusive disease and mechanical biliary obstruction, in which (for unclear reasons) fibrosis can progress more rapidly.

While fibrosis is reversible in its initial stages, progressive fibrosis can lead to cirrhosis. The exact point when fibrosis becomes irreversible is incompletely understood. However, increasing evidence suggests that even early stages of cirrhosis may be reversible [6-11]. Furthermore, an understanding of the molecular mechanisms involved in fibrogenesis has a number of clinical implications, including the development of interventions designed to impede or reverse hepatic fibrosis, some of which are already available [12,13]. Despite significant advances in understanding hepatic fibrosis and defining targets of therapy, there are no antifibrotic drugs yet approved for clinical use in patients with advanced liver disease.

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Literature review current through: Oct 2017. | This topic last updated: Nov 24, 2015.
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