Research project

Primary sclerosing cholangitis in inflammatory bowel disease (IBD)

Status: Ongoing

Sclerosing cholangitis is a chronic inflammatory disease that may lead to fibrosis of the intra- and/or extrahepatic bile ducts in pediatric-onset inflammatory bowel disease.

What we do

About our project

Background information

Liver and/or biliary tract disease develops in a high proportion of patients with inflammatory bowel disease (IBD). A rare example is primary sclerosing cholangitis (PSC), which is an important cause of morbidity and mortality in both children and adults. The disease etiopathogenesis is not clear and this undoubtedly explains why effective medical treatments are still lacking. Both clinical (project 1) and fundamental (project 2) research with a focus on the strong association between IBD and PSC will help gain better understanding of the pathogenesis of the disease and open up new therapeutic perspectives.

Overall aim

Project 1: The natural history of IBD-related liver disease in children in the Netherlands: a retrospective multi-center chart review.

Characterize the clinical, radiological and histological features of children with IBD-related liver disease at disease presentation and identify prognostic variables for a complicated disease course in the first five years after diagnosis.
Compare the outcomes of childhood-onset IBD-related liver disease.
Compare the outcomes of childhood-onset with those of adult-onset IBD-related liver disease.
Provide suggestions for the diagnostics and long term follow-up of this patient group.

Project 2: Identification of microbiota-specific immune responses driving primary sclerosing cholangitis) with concomitant inflammatory bowel disease (IBD).

Research method

Methods Project 1: We reviewed medical records of patients with autoimmune-mediated liver disease under the age of 18 years diagnosed between January 2000 and July 2017. We grouped patients according to biochemical, immunological, radiological and/or histological features (Table S1), into PSC, ASC and AIH. Data were extracted onto an online case report form using Castor EDC.
Methods Project 2:

Determining numbers and phenotypes of immune cells (neutrophils, monocytes, mucosal T cells) in peripheral blood, intestinal tissue and liver tissue;
Determining baseline levels of cytokines of mucosal T-cells from peripheral blood and intestinal biopsies;
Deternining the immunological responses of mucosal T-cells from peripheral blood and intestinal tissue upon re-stimulation with superantigens or microbial peptides;
Identifying Serological parameters (i.e. anti-flagellin antibodies).

Primary-sclerosing