Primary sclerosing cholangitis Digestive System
Conditions
Interventions
This is a single-centre cross-sectional observational cohort study with sample and data collection taking place in line with the routine standard of clinical care visits.
Participants eligible for th
however, it is intended that a single patient is eligible to donate more than one sample type. The total number of participants will be dictated by the number required to meet the target sample size f
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligible participants must fulfil the criteria set out below, as related to the sample type in question. Peripheral blood: 1. Adults (age 18 – 75 years). 2. Be able to provide written (signed) informed consent. 3. Be willing and able to comply with routine clinic visits and study-related procedures. 4. Be able to understand and complete study-related questionnaires. 5. Liver disease populations - participants must have an established diagnosis of any of the following conditions: 5.1. PSC 5.2. PBC 5.3. MASLD 6. IBD alone populations - participants must have an established diagnosis of one of the following, without a concurrent diagnosis of PSC: 6.1. Ulcerative colitis (UC) 6.2. Crohn’s disease with colonic involvement 6.3. IBD unclassified with colonic involvement 7. Healthy controls -defined as participants who do not have present or previous gastrointestinal or liver disease. Participants with functional gastrointestinal disorder (FGID) can be included. This will be clinician defined. Stool: 1. Adults (age 18 – 75 years). 2. Be able to provide written (signed) informed consent. 3. Be willing and able to comply with routine clinic visits and study-related procedures. 4. Be able to understand and complete study-related questionnaires. 5. Liver disease populations: participants must have an established diagnosis of any of the following conditions: 5.1. PSC 5.2. PBC 5.3. MASLD 6. IBD populations: participants must have an established diagnosis of one of the following, without a concurrent diagnosis of PSC: 6.1. Ulcerative colitis (UC) 6.2. Crohn’s disease with colonic involvement 6.3. IBD unclassified with colonic involvement 7. Healthy control populations: defined as participants who do not have present or previous gastrointestinal or liver disease. Participants with functional gastrointestinal disorder (FGID) can be included. This will be clinician defined. Colonic biopsies: 1. Adults (age 18 – 75 years). 2. Be able to provide written (signed) informed consent. 3. Be willing and able to comply with routine clinic visits and study-related procedures. 4. Be able to understand and complete study-related questionnaires. 5. Liver disease populations: participants must have an established diagnosis of PSC. 6. IBD population: participants must have an established diagnosis of one of the following, without a concurrent diagnosis of PSC: 6.1. Ulcerative colitis (UC) 6.2. Crohn’s disease with colonic involvement 6.3. IBD unclassified with colonic involvement 7. Healthy control populations: 7.1. Participants without a diagnosis of PSC or IBD, attending for a colonoscopy who do not meet the exclusion criteria. Biliary aspirates/biopsies: 1. Adults (age 18 – 75 years). 2. Be able to provide written (signed) informed consent. 3. Be willing and able to comply with routine clinic visits and study-related procedures. 4. Be able to understand and complete study-related questionnaires. 5. Established diagnosis of PSC.
Exclusion criteria
Exclusion criteria: Here is the revised text with the requested numbering system: Eligible participants must fulfill the criteria set out below, as related to the sample type in question. Peripheral blood: 1. Liver transplant recipients. 2. Evidence of acute or chronic liver disease not listed in the inclusion criteria, including, but not limited to: 1.1. Secondary sclerosing cholangitis 1.2. IgG4-related cholangitis 1.3. Viral hepatitis 1.4. Alcohol-related liver disease 1.5. Drug-induced liver disease or drug-induced sclerosing cholangitis 1.6. Hereditary haemochromatosis 1.7. Alpha-1-antitrypsin disease 1.8. Wilson disease 1.9. Budd-Chiari Syndrome *Individuals with autoimmune hepatitis, concomitant IBD, and overlapping features of sclerosing cholangitis are eligible and may be recruited to the PSC group.* 3. Evidence of acute or chronic gastrointestinal disease not listed in the inclusion criteria. 4. A history of malignancy within the prior 3 years, except for individuals with: 1.1. Prior gallbladder cancer, with gallbladder removal, and without evidence of recurrence or disseminated/metastatic disease. 1.2. Prior colonic cancer, with local resection, and without evidence of recurrence or disseminated/metastatic disease. 1.3. Prior non-melanomatous skin cancer that has been resected, without evidence of recurrence or disseminated/metastatic disease. 5. If the potential participant is a member of the clinical site study team and/or his/her immediate family. 6. Women who are pregnant or less than 12 weeks post-partum. Stool: 1. Liver transplant recipients. 2. Evidence of acute or chronic liver disease not listed in the inclusion criteria, including, but not limited to: 1.1. Secondary sclerosing cholangitis 1.2. IgG4-related cholangitis 1.3. Viral hepatitis 1.4. Alcohol-related liver disease 1.5. Drug-induced liver disease or drug-induced sclerosing cholangitis 1.6. Hereditary haemochromatosis 1.7. Alpha-1-antitrypsin disease 1.8. Wilson disease 1.9. Budd-Chiari Syndrome *Individuals with autoimmune hepatitis, concomitant IBD, and overlapping features of sclerosing cholangitis are eligible and may be recruited to the PSC group.* 3. Evidence of acute or chronic gastrointestinal disease not listed in the inclusion criteria. 4. A history of malignancy within the prior 3 years, except for individuals with: 1.1. Prior gallbladder cancer, with gallbladder removal, without evidence of recurrence or disseminated/metastatic disease. 1.2. Prior colonic cancer, with local resection, without evidence of recurrence or disseminated/metastatic disease. 1.3. Prior non-melanomatous skin cancer that has been resected, without evidence of recurrence or disseminated/metastatic disease. 5. Previous colonic or small bowel resection. 6. If the potential participant is a member of the clinical site study team and/or his/her immediate family. 7. Women who are pregnant or less than 12 weeks post-partum. Colonic biopsies: 1. Liver transplant recipients. 2. Evidence of acute or chronic liver disease not listed in the inclusion criteria, including, but not limited to: 1.1. Secondary sclerosing cholangitis 1.2. IgG4-related cholangitis 1.3. Viral hepatitis 1.4. Alcohol-related liver disease 1.5. Drug-induced liver disease or drug-induced sclerosing cholangitis 1.6. Hereditary haemochromatosis 1.7. Alpha-1-antitrypsin diseas
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Cellular and molecular signatures in immune, stromal, and epithelial cell populations in bile, colon and peripheral blood will be measured using the following methods at a single time point: 1.1. Transcriptional profiling through single-cell RNA sequencing of colonic biopsies, and biliary samples (biliary aspirates and/or brushings and/or biopsies) 1.2. Transcriptional profiling through bulk RNA sequencing of peripheral blood mononuclear cells, colonic biopsies, and biliary samples (biliary aspirates and/or brushings and/or biopsies) 1.3. Cellular profiling by multi-parameter flow cytometry on peripheral blood mononuclear cells 1.4. Cellular profiling by multi-parameter flow cytometry on immune cells isolated from biliary and colon samples 2. Human genetic variants that are associated with PSC, its disease severity, and progressive (high-risk) disease phenotypes will be measured genetic association studies using whole-exome sequencing and/or array genotyping to identify single variant and/or gene-based burden associations to disease risk, severity, progression, and related clinical traits using the following methods at a single time point | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Plasma proteome associated with PSC measured using proteomic profiling of peripheral blood plasma using Olink and/or complementary technologies to identify proteins that are differentially expressed at a single time point 2. Associations between the plasma proteome in PSC and disease severity measured using protein and/or RNA profiling using in situ hybridization/immunohistochemistry measures on colon and biliary biopsies at a single time point 3. T-cell receptor (TCR) repertoire in PSC versus disease controls and healthy controls measured using TCR sequencing of blood, biliary brushings/biopsies, and colonic biopsies for TCR repertoire analysis at a single time point | — |
Countries
England, United Kingdom
Contacts
Public ContactPalak Trivedi
Outcome results
None listed