Intestinal fibrosis in inflammatory bowel disease - Current knowledge and future perspectives

Background and aims: Intestinal fibrosis is a common complication of IBD that can become seriously symptomatic and may require surgical intervention if stricture formation ensues. This review discusses existing and developing knowledge of intestinal fibrosis and its implications for therapy. Methods: Review of the literature, personal communications, unpublished observations. Results: Known mechanisms of intestinal fibrosis include fibroblast proliferation and migration, activation of stellate cells, and extraintestinal fibroblast recruitment. However, novel mechanisms are being uncovered, including epithelial-to-mesenchymal transition, endothetialto-mesenchymal transition, pericyte differentiation, and fibrocyte recruitment. Most of the traditional and novel mechanisms underlying intestinal fibrosis are associated to the presence of chronic inflammation, but is also possible that fibrosis develops independently of persistent immune activation in the gut. At the moment, the development of preventive, non-interventional, and more effective management of intestinal fibrosis is hampered by the tack of a greater knowledge of its basic pathophysiology and predisposing factors. Conclusions: It is reasonable to expect that therapy of IBD-associated fibrosis will radically improve once the underlying mechanisms are better understood, and therapeutic modalities will emerge that prevent or reverse this complication of IBD. (C) 2008 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.