Fibrosis in Ulcerative Colitis is Directly Linked to Severity and Chronicity of Mucosal Inflammation

Background: Fibrosis in ulcerative colitis has remained largely unexplored despite its clinical implications.

Aims: This cross-sectional study was aimed at characterising the presence, anatomical location and degree of ulcerative colitis-associated fibrosis and its possible link to clinical parameters.

Methods: Seven hundred and six individual tissue cross-sections derived every 10 cm along the length of 89 consecutive Ulcerative colitis colectomy specimens were examined and compared to Crohn's disease colitis, diverticular disease and uninvolved areas from colorectal cancer patients. Degree of inflammation, fibrosis and morphometric measurements of all layers of the intestinal wall were evaluated. Three gastrointestinal pathologists independently assessed colon sections stained with haematoxylin and eosin, Masson trichrome and Sirius red. Clinical data were collected prospectively.

Results: Submucosal fibrosis was detected in 100% of ulcerative colitis colectomy specimens, but only in areas affected by inflammation. Submucosal fibrosis was associated with the severity of intestinal inflammation (Spearman correlations rho (95% confidence interval): 0.58 (P < 0.001) and histopathological changes of chronic mucosal injury, but not active inflammation. Colectomy for refractory disease rather than presence of dysplasia was associated with increased fibrosis and a thicker muscularis mucosae, whereas a thinner muscularis mucosae was associated with anti-tumour necrosis factor therapy. No feature on endoscopic mucosal biopsies could predict the underlying amount of fibrosis or the thickness of the muscularis mucosae.

Conclusions: A significant degree of fibrosis and muscularis mucosae thickening should be considered as common complications of chronic progressive ulcerative colitis. These features may have clinical consequences such as motility abnormalities and increased wall stiffness.