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Emerging therapies for hepatic fibrosis

Author
Scott L Friedman, MD
Section Editor
Bruce A Runyon, MD
Deputy Editor
Anne C Travis, MD, MSc, FACG, AGAF

INTRODUCTION

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. 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".)

FIBROSIS REVERSIBILITY

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 [3] and hepatitis C [4], at least 70 percent of patients had reversal of cirrhosis following successful antiviral therapies.

The development of targeted therapies is moving closer to reality (table 1) [5]. 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.

As a general rule, the currently available antifibrotic therapies have been directed against suppressing hepatic inflammation rather than subduing fibrosis. In the future, targeting of stellate cells and fibrogenic mediators will be a mainstay of therapy. Points of therapeutic intervention may include efforts to remove the injurious stimuli, suppress hepatic inflammation, downregulate stellate cell activation, and promote matrix degradation.

                              

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Literature review current through: Nov 2016. | This topic last updated: Thu Jun 12 00:00:00 GMT+00:00 2014.
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