Small duct primary sclerosing cholangitis without inflammatory bowel disease is genetically different from large duct disease
Open accessAbstract
Background & Aims: Small duct primary sclerosing cholangitis (PSC) is phenotypically a mild version of large duct PSC, but it is unknown whether these phenotypes share aetiology. We aimed to characterize their relationship by investigating genetic associations in the human leucocyte antigen (HLA) complex, which represent the strongest genetic risk factors in large duct PSC. Methods: Four classical HLA loci (HLA‐A, HLA‐B, HLA‐C and HLA‐DRB 1) were genotyped in 87 small duct PSC patients, 485 large duct PSC patients and 1117 controls across three geographical regions. Results: HLA‐DRB 1*13:01 (OR = 2.0, 95% CI 1.2–3.4, P = 0.01) and HLA‐B*08 (OR = 1.6, 95% CI 1.1–2.4, P = 0.02) were significantly associated with small duct PSC compared with healthy controls. Based on the observed frequency of HLA‐B*08 in small duct PSC, the strongest risk factor in large duct PSC, an estimated 32% (95% CI 4–65%) of this population can be hypothesized to represent early stages or mild variants of large duct PSC. This subgroup may be constituted by small duct PSC patients with inflammatory bowel disease (IBD), which greatly resembled large duct PSC in its HLA association. In contrast, small duct PSC without IBD was only associated with HLA‐DRB 1*13:01(P = 0.03) and was otherwise distinctly dissimilar from large duct PSC. Conclusions: Small duct PSC with IBD resembles large duct PSC in its HLA association and may represent early stages or mild variants of large duct disease. Different HLA associations in small duct PSC without IBD could indicate that this subgroup is a different entity. HLA‐DRB 1*13:01 may represent a specific risk factor for inflammatory bile duct disease.
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Based on specific genetic associations, small duct PSC may represent very early stages of PSC in patients who also have inflammatory bowel disease, but not in those without.
“Based on specific genetic associations, small duct PSC may represent very early stages of PSC in patients who also have IBD, but not in those without.53”
From EASL Clinical Practice Guidelines on sclerosing cholangitis (2022) · cites this paper as [53]
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- Authors
- Næss, S., Björnsson, E., Anmarkrud, J. A., Mamari, S. A., Juran, B. D., Lazaridis, K. N., Chapman, R., Bergquist, A., Melum, E., Marsh, S. G. E., Schrumpf, E., Lie, B. A., Boberg, K. M., Karlsen, T. H., & Hov, J. R.
- Affiliations
- Oslo University Hospital (NO)
- Division of Gastroenterology and Hepatology Department of Internal Medicine Landspitali University Hospital Reykjavik Iceland
- Sultan Qaboos Hospital (OM)
- Mayo Clinic (US)
- John Radcliffe Hospital (GB)
- Karolinska University Hospital (SE)
- Anthony Nolan (GB)
- Corresponding author
- Hov, Johannes R.
- ORCID
- Venue
- Liver International
- Publisher
- Wiley
- Published
- 2014-03-07
- Volume
- 34
- Issue
- 10
- Pages
- 1488-1495
- ISSN
- 0106-9543 (ISSN-L)
- 1478-3223
- 1478-3231
- PMC
- PMC4128902
- OpenAlex
- W2080459269
- Cited by
- 54
- References
- 36
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 7 · 2016: 4 · 2015: 6 · 2014: 1
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Hirsla (Landspítali University Hospital) (submittedVersion)
- Funders
- Norwegian PSC Research Center
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- National Human Genome Research Institute
- National Institute of Child Health and Human Development
- Juvenile Diabetes Research Foundation International (U01 DK062418)
- NIH (DK084960)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- primary sclerosing cholangitis, inflammatory bowel disease, HLA-B*08, HLA association, genetic risk factors, disease phenotypes
- MeSH terms
- Genotype, United Kingdom, Humans, Norway, Phenotype, Risk Factors, Sweden, United States, Cholangitis, Sclerosing, Inflammatory Bowel Diseases, HLA-B8 Antigen, Linkage Disequilibrium, Odds Ratio, HLA-DRB1 Chains
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