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Emerging therapies for hepatic fibrosis

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


Hepatic fibrosis is a scarring response to liver damage, which may be considered beneficial since it can encapsulate injury. However, in doing so liver function may ultimately become impaired [1].

There has been exciting progress in understanding hepatic fibrosis, which 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 [1,2]. An understanding of these mechanisms has a number of clinical implications, including the development of interventions designed to impede or reverse hepatic fibrosis, some of which are already available [3]. Perhaps the greatest change in the field of antifibrotic therapy has been the intense focus on NASH as a therapeutic target, reflecting the growing appreciation of this disease as a public health threat [4], combined with the realization that with cures for hepatitis C virus (HCV) in the majority of patients due to direct acting antiviral therapies, fewer HCV and hepatitis B virus patients will need antifibrotic therapies, although in reality cirrhosis due to HCV remains a large unmet need [5]. This topic review will focus on possible future treatments aimed at impeding or reversing fibrosis. The pathogenesis of hepatic fibrosis is presented elsewhere. (See "Pathogenesis of hepatic fibrosis".)


The exact moment at which fibrosis becomes irreversible is unknown, either in terms of a histologic marker or a specific change in the matrix composition or content. Dense cirrhosis with nodule formation, portal hypertension, and early liver failure is generally considered irreversible, but less advanced lesions can show remarkable reversibility when the underlying cause of the liver injury is controlled and possibly by other therapeutic interventions. In studies of patients with hepatitis B hepatitis C, and NASH, up to 70 percent of patients had reversal of cirrhosis following successful antiviral therapies or bariatric surgery, respectively [6-8].

The development of targeted therapies is moving closer to reality (table 1) [3,9]. The ideal drug would be the one which could be easily delivered, is well tolerated, has high liver specificity, and promotes the resorption of excess interstitial matrix without abolishing the salutary effects of the normal hepatic extracellular matrix. The hope is not necessarily to eliminate fibrosis entirely, but rather to attenuate its development so that patients with chronic liver disease do not succumb to the end organ failure that it creates (eg, portal hypertension, ascites, liver failure). While no therapy yet meets these goals, the framework for developing such treatments is in place and progress is accelerating.

As a general rule, the currently available antifibrotic therapies have been directed against suppressing hepatic inflammation or injury rather than subduing fibrosis. However, targeting of stellate cells and fibrogenic mediators has emerged as an equally promising complement to therapies that reduce injury. Points of therapeutic intervention may include efforts to remove the injurious stimuli, suppress hepatic inflammation, downregulate stellate cell activation, and promote matrix degradation [10].

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Literature review current through: Nov 2017. | This topic last updated: Oct 27, 2017.
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