Primary Sclerosing Cholangitis in Children

To characterize the major phenotypes of PSC including patients with large duct or small duct disease, with and without Inflammatory Bowel Disease (IBD), and with and without Auto Immune Hepatitis (AIH)

Data will be collected on all phenotypes of PSC but attention is focused on how the intestinal inflammation and clinical activity of Inflammatory Bowel Disease (IBD) affect the progression of PSC, better classification of patients with features of Auto Immune Hepatitis (AIH), and the implications of bacterial cholangitis amongst all PSC phenotypes. Collection of retrospective clinical and laboratory data from the time of diagnosis of PSC and annual timepoints thereafter. Information regarding clinically important timepoints, laboratory data and FibroScan Liver Stiffness Measurements (LSM) are collected prospectively. Slides/images (if available) from each liver biopsy obtained at the time of diagnosis of PSC and thereafter and from the explanted liver recovered at the time of liver transplantation will undergo central review. Cholangiography results (MRCP, ERCP) will also undergo central review.

To identify the symptoms of PSC in children and the affects of those symptoms on the functional health of children.

Identify deficits in the functional health of children with PSC and explore the association of these functional parameters with biochemical markers of liver disease severity and IBD activity. Symptoms and the impact the symptoms on the functional health of children is measured through the use of "Patient Reported Outcomes" and performance-based metrics. The burden of disease on the quality of life for children with PSC is measured utilizing the Peds-QL questionnaires (parent proxy and self-report). Child self-report: 8-12 years, and 13-18 years. Young adult self-report: 18-25 years. Parent proxy report: 2-4 years, 5-7 years, 8-12 years, and 13-17 years. Itch and fatigue identified as predominant symptoms in PSC are measured through the administration (at every visit) of the 5-D ITCH scale and the PedsQL multidimensional fatigue and PROMIS Sleep Scales. Frailty parameters in children with PSC are measured through the Fried frailty criteria at every visit.

Utilizing imaging modalities measuring liver fibrosis, and large duct injury to correlate with other markers of fibrosis and biliary injury and predict progression of disease.

The imaging modalities are utilized to explore the two pathophysiological processes of PSC, liver fibrosis and bile duct damage. Quantitative MRI techniques may be more sensitive to disease progression than standard clinical and laboratory tests, as the liver and bile ducts are being explored directly. All participants will undergo a liver stiffness measurement (LSM) at baseline and annually. In addition to the LSM, participants who are eligible (eligibility criteria are different than those for the overall study) will be asked to undergo a research MRI at the baseline, Year 1 and Year 5 visits.

Development of a repository for formalin fixed paraffin embedded (FFPE) liver biopsy tissue, serum, plasma, peripheral blood mononuclear cells (PBMCs), DNA and stool.

Samples of peripheral blood mononuclear cells (PBMC), serum, plasma, DNA and stool are collected from participants at baseline and serum/plasma will be collected annually. In addition, any liver tissue previously collected or collected for clinical purposes in the future will be analyzed along with the PBMC, serum, plasma, DNA and stool within future mechanistic ancillary studies related to the diagnostic/prognostic biomarkers, and genetic, immune and microbial theories of pathogenesis.