Results of the 4th Scientific Workshop of the ECCO (Group II): Markers of intestinal fibrosis in inflammatory bowel disease

Abstract

The fourth scientific workshop of the European Crohn's and Colitis Organization (ECCO) focused on intestinal fibrosis in inflammatory bowel disease (IBD). The objective was to better understand basic mechanisms and markers of intestinal fibrosis as well as to suggest new therapeutic targets to prevent or treat fibrosis. The results of this workshop are presented in three separate manuscripts. This section describes markers of fibrosis in IBD, identifies unanswered questions in the field and provides a framework for future studies addressing the unmet needs in the field of intestinal fibrosis.

Biomarkers of intestinal fibrosis – one step towards clinical trials for stricturing inflammatory bowel disease

“…1 In particular, transmural damage induced by chronic inflammation in Crohn's disease causes tissue remodelling of the entire intestinal wall, which is characterized by an excessive deposition of extracellular matrix (ECM) components due to an imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the context of a massive activation of ECM-producing cells responsible for the excessive deposition of fibrillar collagens, thus leading to tissue fibrosis as end-stage complication of Crohn's disease. 2,3 Increased amount of collagen and thickening of the muscularis mucosae have been also identified in the colon of ulcerative colitis patients both with short-and long-standing disease, with consequent shortening and increased rigidity of the colon.…”

“…9 Currently, there are no predictors able to estimate the risk of developing intestinal fibrosis in IBD patients. 1 All the proposed noninvasive biomarkers of intestinal fibrosis, including gene polymorphisms or variants, microRNAs (miRs), ECM components, growth factors and anti-microbial antibodies ( Figure 1 Nucleotide-binding oligomerization domain (NOD)2 variants, which imply loss of binding between NOD2 and the bacterial cell wall component muramyl dipeptide (MDP), polymorphisms of the chemokine fractalkine receptor CX3CR1, variants in the toll like receptor (TLR)4, in the autophagy-related-16L1 (ATG16L1) and in the interleukin 23 receptor (IL23R) induce chronic inflammation leading to stricture development. Excessive deposition of ECM components, which consist of fibronectin, laminin, collagen and its propeptide or telopeptide -such as N-terminal propeptide of type III collagen (PIIINP), C-terminal propeptide of type I collagen (PICP) and C-terminal telopeptide of type I collagen (ITCP) -and alterated tissue remodelling are also due to a specific single nucleotide polymorphism in matrix metalloproteinase (MMP)-3 gene, which loses its proteolytic activity on ECM, and to abnormal expression of tissue inhibitor of matrix metalloproteinases (TIMP)-1.…”

“…Biomarkers of intestinal fibrosis would be useful in order to stratify patients according to their risk of stricture development and to identify early stages of fibrosis with the aim of optimizing the therapeutic management. 1 Patients with known risk factors for severe disease course, that is, age below 40 years at diagnosis, early requirement of steroids and perianal disease, 10 have an increased rate of fibrostenotic complications, thus they should be more strictly followed up.…”

New endoscopic approach of anti-fibrotic therapy for inflammatory bowel disease

“…This implies that control of intestinal inflammation alone does not necessarily affect the associated fibrotic process. There are no standard anti-fibrotic medical treatments for IBD, and dilation of intestinal strictures with endoscopy or surgical treatment plays an important role in managing the strictures of IBD (3)(4)(5)(6)(7)(8)(9)(10). Therefore, treatment goals of IBD include not only symptom control alone but prevention of intestinal fibrosis with structural bowel damage, that is, bowel tissue remodeling (11,12).…”

“…Despite a great progress in modern anti-inflammatory therapies including immunosuppressants and biologics, intestinal fibrosis is a frequent complication in the natural history of IBD, as up to onethird of CD patients and about 5% of UC patients develop Review Article on Endoscopic Therapy strictures in the clinical course of the disease (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). In CD, chronic inflammation induces transmural damage which causes accumulation of extracellular matrix (ECM) and expansion of mesenchymal cells, finally leading to intestinal strictures.…”