Clinically suitable approach for gene-mediated therapy of cirrhosis.

Abstract Persistent injury to the liver can cause chronic inflammation and dysregulated deposition of extracellular matrix (ECM), leading to accumulation of fibrotic scar tissue and eventually cirrhosis. While fibrosis is a normal wound healing response, in excess, it can further injure tissue and activate pro-fibrotic cells, resulting in a positive feedback loop. Scar tissue is not static, ECM remodeling is a dynamic and regulated process that holds promise for targeted intervention of fibrotic disease. Furthermore, recent observations suggest the potential for the 'reversal' of advanced liver disease upon removal of the source of injury. In cirrhosis, aggressive removal of scar tissue would likely be needed to halt the positive feedback loop and create space for healthy hepatocyte growth. One hypothesis for achieving this is the introduction of ECM regulating enzymes, such as the collagenase Matrix Metalloprotienase-8 (MMP-8), thus shifting the balance of pro-fibrotic versus anti-fibrotic components, break