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Liver fibrosis and cirrhosis result from the majority of chronic liver insults and represent a common and difficult clinical challenge of worldwide importance. At present, the only curative treatment for end stage cirrhosis is transplantation, but even in the developed world, the number of donor organs available and the clinical condition of the potential recipient limit the applicability of this technique. The alternative clinical course is one familiar to gastroenterologists—that of a progressive damage limitation exercise in which the complications of fibrosis and cirrhosis are treated with greater or lesser success. The development of fibrosis, and particularly cirrhosis, is associated with a significant morbidity and mortality. Thus, there is a considerable imperative to develop antifibrotic strategies that are applicable to liver fibrosis. Such an approach is attractive precisely because it is aimed at the final common pathological pathway of chronic liver disease, regardless of aetiology. However, because fibrotic liver disease may not present clinically until an advanced or cirrhotic stage, the possibility of reversing the fibrosis is an essential issue for developing therapeutic approaches.
Liver fibrosis represents the wound healing response of the liver, as such it demonstrates generic aspects that characterise tissue healing elsewhere in the body — a wound healing response that is dynamic and has the potential to resolve without persistent scarring. This may seem at odds with the clinical impression that advanced fibrosis and cirrhosis are at best irreversible and at worst progressive. However, recent developments in our understanding of the process of hepatic fibrogenesis confirm that the process is dynamic with respect to both cell and extracellular matrix (ECM) turnover and suggest that a capacity for recovery from advanced cirrhosis and fibrosis is possible. Moreover, with the advent of effective antiviral therapies, biopsy documented examples of improvements in fibrosis and in some examples resolution, including …