Background: Primary sclerosing cholangitis (PSC) is a progressive liver disease associated with inflammatory bowel disease (IBD). The percentage of PSC patients diagnosed with concomitant IBD varies considerably between studies. This raises the question whether all PSC patients would show intestinal inflammation if screened thoroughly, even in the absence of symptoms.
Methods: To address this question, we collected intestinal biopsies of healthy controls (n = 34), PSC (n = 25), PSC-IBD (n = 41), and IBD (n = 51) patients in a cross-sectional study and carried out cytokine expression profiling, 16S sequencing, in-depth histology, and endoscopy scoring.
Results: We found that the vast majority of PSC patients even without clinically manifest IBD showed infiltration of immune cells and increased expression of IL17A and IFNG in intestinal biopsies. However, expression of IL10 and FOXP3 were likewise increased, which may explain why these PSC patients have intestinal inflammation only on a molecular level. This subclinical inflammation in PSC patients was focused in the distal colon, whereas PSC-IBD patients showed inflammation either at the distal colon or on the right side of the colon and the terminal ileum. Furthermore, we observed that PSC patients without IBD showed signs of dysbiosis and exhibited a distinct microbial profile compared with healthy controls.
Conclusions: We found a gradient of intestinal inflammation in the vast majority of PSC patients even in the absence of IBD. Thus, further studies evaluating the effect of anti-inflammatory therapies in PSC patients and their impact on the emergence of clinically manifest IBD and colorectal cancer development are needed.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/ibd/izad137 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Hepatobiliary manifestations of inflammatory bowel disease in Saudi Arabia: A retrospective analysis.
Saudi Med J
January 2025
From the Department of Surgery (Aljiffry, Dahal, Baeisa, Alzahrani, Saleem, Alshahrany), from the Department of Medicine (Hijji, Alsahafi, Alghamdi, Mosli), from the Faculty of Medicine (Aljiffry, Daha, Baeisa, Alzahrani, Alshahrany, Hijji, Alsahafi, Saleem, Alghamdi, Mosli), King Abdulaziz University, from the Inflammatory Bowel Disease Research Group (Alsahafi, Mosli), and from the Gastrointestinal Oncology Unit (Saleem, Alghamdi), King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia.
Objectives: To evaluate the features and frequency of hepatobiliary diseases in individuals with Inflammatory bowel disease (IBD).
Methods: This retrospective study included all IBD patients at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The primary focus was on the prevalence of hepatobiliary diseases, such as primary sclerosing cholangitis (PSC), non-alcoholic fatty liver disease (NAFLD), autoimmune hepatitis (AIH), and others.
Diagnosing Crohn's Disease in Presumed Cryptoglandular Perianal Fistulas: An Expert Delphi Consensus on Early Identification of Patients at Risk of Crohn's Disease in Perianal Fistulas (PREFAB).
J Crohns Colitis
January 2025
Department of Surgery, Flevoziekenhuis, Almere, The Netherlands.
Background: The aim of this Delphi study was to reach consensus on a new clinical decision tool to help identify or exclude Crohn's disease (CD) in patients with perianal fistula(s) (PAF).
Methods: A panel of international experts in the field of proctology/Inflammatory Bowel Disease (IBD) were invited to participate. In the first round (electronic survey), participants were asked to anonymously provide their opinion probing 1) the relevance and use of clinical characteristics suggestive of underlying CD, 2) the use of faecal calprotectin (FCP) for screening for CD and 3) on the diagnostic work-up for CD in PAF patients with raised clinical suspicion.
The Differential Complement, Fc and Chemokine Receptor Expression of B Cells in IgG4-Related Pancreatobiliary Disease and Primary Sclerosing Cholangitis and Its Relevance for Targeting B Cell Pathways in Disease.
Biomedicines
December 2024
Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK.
Immune-mediated liver and biliary conditions, such as IgG4-related pancreatobiliary disease (IgG4-PB) and a subset of primary sclerosing cholangitis (PSC- high(h)IgG4), exhibit increased IgG4 levels in the blood. The relative expression of IgG4+ and IgG1+ B cells in the blood and the expression of complement and Fc receptors on these IgG1+ and IgG4+ B cells in IgG4-PB and PSC have not been previously described. We hypothesised that the patterns of expression of these cells and their receptors would differ, are relevant to disease pathogenesis and may represent therapeutic targets.
View Article and Find Full Text PDFMitochondrial dysfunction and lipid alterations in primary sclerosing cholangitis.
Scand J Gastroenterol
January 2025
Norwegian PSC Research Centre, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Objectives: Indications of mitochondrial dysfunction are commonly seen in liver diseases, but data are scarce in primary sclerosing cholangitis (PSC). Analyzing circulating and liver-resident molecules indirectly reflecting mitochondrial dysfunction, we aimed to comprehensively characterize this deficit in PSC, and whether this was PSC specific or associated with cholestasis.
Materials And Methods: We retrospectively included plasma from 191 non-transplant patients with large-duct PSC and 100 healthy controls and explanted liver tissue extracts from 24 PSC patients and 18 non-cholestatic liver disease controls.
FAecal micRobiota transplantation in primary sclerosinG chOlangitis (FARGO): study protocol for a randomised, multicentre, phase IIa, placebo-controlled trial.
BMJ Open
January 2025
National Institute of Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC) Center for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, England, UK
Introduction: Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). The strong association between gut and liver inflammation has driven several pathogenic hypotheses to which the intestinal microbiome is proposed to contribute. Pilot studies of faecal microbiota transplantation (FMT) in PSC and IBD are demonstrated to be safe and associated with increased gut bacterial diversity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!