This paper is the first in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the diagnosis and management of Crohn's disease and concerns the methodology of the consensus process, and the classification, diagnosis and medical management of active and quiescent Crohn's disease. Surgical management as well as special situations including management of perianal Crohn's disease of this ECCO Consensus are covered in a subsequent second paper [Gionchetti et al JCC 2016].

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Activated fibroblasts are key contributors to the fibrotic extracellular matrix accumulation during liver fibrosis. The origin of such fibroblasts is still debated, although several studies point to stellate cells as the principal source. The role of adult hepatocytes as contributors to the accumulation of fibroblasts in the fibrotic liver is yet undetermined. Here, we provide evidence that the pro-fibrotic growth factor, TGF-␤1, induces adult mouse hepatocytes to undergo phenotypic and functional changes typical of epithelial to mesenchymal transition (EMT). We perform lineage-tracing experiments using AlbCre. R26RstoplacZ double transgenic mice to demonstrate that hepatocytes which undergo EMT contribute substantially to the population of FSP1-positive fibroblasts in CCL 4 -induced liver fibrosis. Furthermore, we demonstrate that bone morphogenic protein-7 (BMP7), a member of the TGF␤ superfamily, which is known to antagonize TGF␤ signaling, significantly inhibits progression of liver fibrosis in these mice. BMP7 treatment abolishes EMT-derived fibroblasts, suggesting that the therapeutic effect of BMP7 was at least partially due to the inhibition of EMT. These results provide direct evidence for the functional involvement of adult hepatocytes in the accumulation of activated fibroblasts in the fibrotic liver. Furthermore, our findings suggest that EMT is a promising therapeutic target for the attenuation of liver fibrosis.Liver cirrhosis is still the sixth most common cause of death among United States citizens from ages 25 to 64 (1). Cirrhosis of the liver and its functional loss, which is caused by a progressive fibrosis, occurs due to a variety of insults, such as viral hepatitis, metabolic or autoimmune diseases, toxic injury, or congenital abnormalities (1-3). Fibrosis in the liver, as with fibrosis in other organs such as lung, kidney, heart, or skin, is described as excessive deposition of extracellular matrix (ECM), 6 which leads to the destruction of organ structure and impairment of organ function. Activated fibroblasts are key mediators of organ fibrosis. In the fibrotic liver, such activated fibroblasts are considered to derive via activation and proliferation of resident stellate cells and periportal fibroblasts (1, 2, 4 -9). Because specific treatments to halt progressive fibrosis of the liver are not yet available, further understanding of the underlying pathogenic mechanisms involved in the accumulation of scar-forming fibroblasts is required.Evidence is evolving that fibroblasts are more heterogeneous than traditionally thought (10) and recent studies reveal additional mechanisms such as recruitment of bone marrow-derived cells and conversion of resident epithelia as contributors to the accumulation of activated fibroblasts in fibrotic tissues (10,11). In this study, we attempted to gain further insights into the role of adult hepatocytes, the parenchymal epithelial cells of the liver, in the accumulation of fibroblasts in the inflamed liver. A direct contribution of hepatocytes to liver fibr...