Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associated With Course of Primary Sclerosing Cholangitis
Primary sclerosing cholangitis (PSC) is a challenging disease to investigate.
It’s rare, so it can be difficult to include enough patients in each study to ensure robust results. Moreover, it has long been recognised that there are different kinds of PSC, but up till recently they’ve not been clearly defined. Indeed, many previous studies have evaluated different groups of patients all together, which runs the risk of skewing research findings, and potentially even masking the effects of potential therapies that could provide benefit in certain populations.
Research published in March 2017 by the International PSC Study Group (iPSCsg), joint first authored by Dr Palak Trivedi (Birmingham, UK), who is a key investigator in UK-PSC, and Dr Tobias Weismüller (Bonn, Germany), looked back at the medical data of 7121 patients with PSC from 1980 to 2010 from 17 different countries. This represents a huge international collaboration.
The research team were able to confirm the long-held view that particular factors affect rate of progression of PSC; specifically, the age at which PSC is diagnosed, bile duct phenotype (which bile ducts are affected), and the subtype of concurrent IBD (ulcerative colitis, Crohn’s disease, or neither). Through robust statistical analysis, the investigators showed not only what those factors are, but also how and to what extent they may impact the clinical course of PSC.
What factors were found to affect progression of PSC and hepatopancreatobiliary (HPB) cancer risk?
- Age at diagnosis: a much lower incidence of HPB cancer was found in patients diagnosed with PSC at a younger compared to older age.
- Small duct PSC was associated with a lower risk of progression of PSC and a very low risk of HPB cancer than classical PSC.
- Patients with PSC and overlapping features of autoimmune hepatitis rarely developed HPB cancer, but experience a similar rate of liver disease progression compared to classical PSC.
- PSC and concurrent Crohn’s Disease or no IBD were both associated with a lower risk of liver disease progression and a lower risk of developing HPB cancer than patients with ulcerative colitis.
When asked to describe the key findings of the study, Dr. Trivedi told PSC Support:
"The results of the IPSCSG study may allow doctors to provide a more individualised assessment for patients in terms of the rate of disease progression; and also the risk of developing bile duct malignancy, which has direct implications in evaluating future cancer surveillance strategies. Perhaps most striking, we found that the development of ulcerative colitis is a critical determinant of liver disease progression, which stresses the importance of a good colonoscopy in all newly diagnosed patients with PSC."
Talking about the impact of the study findings on research, Dr. Trivedi continued by explaining that,
"Additionally, our study could refine the way in which patients are studied in future clinical trials, as we can now clearly see different patterns of disease behaviour emerge. We identify individuals at high risk (large bile duct disease with concurrent ulcerative colitis), an intermediate risk group (those with without gut inflammation, or who have Crohn's disease), and a relatively low risk population (patients with only the small bile ducts in the liver involved). When evaluating the impact of new potential therapies in PSC, we must be therefore be mindful that the rates of disease progression vary according to phenotype, and future analysis must be refined by individual patient groups."
All patients of any age with PSC in the UK are welcome to join the UK-PSC Study. There are now 221 centres or hospitals signed up to take PSC patients' biological samples already. Nearly 2,500 UK PSC patients are registered and our results have been combined with those collected internationally via the International PSC Study Group in studies like this one. Please e-mail the UK-PSC Project Manager (or call 0121 371 8101) to join).
The study is published in the journal 'Gastroenterology'.
Weismuller TJ, Trivedi PJ, Bergquist A, Imam M, Lenzen H, Ponsioen CY, et al. Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis. Gastroenterology. 2017;152(8):1975-84 e8. Epub 2017/03/10. doi: 10.1053/j.gastro.2017.02.038. PubMed PMID: 28274849; PubMed Central PMCID: PMCPMC5546611.
Written by Martine Walmsley and Dr. Palak Trivedi, 11 March 2017