Primary Sclerosing Cholangitis (PSC) – Northern Ireland Rare Disease Partnership

Primary Sclerosing Cholangitis (PSC)

What is PSC?

PSC is short for primary sclerosing cholangitis, a rare, immune-mediated liver disease that affects the bile ducts and liver^[1],^[2]. In PSC, the bile does not flow properly due to obstruction/narrowing (strictures) in the bile ducts inside and/or outside the liver.

Even though PSC was first described over 150 years ago in 1867, there is still no cure or known treatments to slow or stop the disease worsening or to reduce the risk of complications. Indeed, Professor Michael Manns, a leading PSC expert, named PSC ‘the last black box in hepatology’.

PSC is a rare complex disease and is not easy to explain. This graphic and video provide a basic, easy to understand and shareable explanation of PSC.

^[1] Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. The Lancet. 2013;382(9904):1587-99. doi: 10.1016/s0140-6736(13)60096-3.

^[2] Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis – a comprehensive review. J Hepatol. 2017;67(6):1298-323. Epub 2017/08/15. doi: 10.1016/j.jhep.2017.07.022. PubMed PMID: 28802875.

^[1] Hirschfield GM, Karlsen TH, Lindor KD, Adams DH. Primary sclerosing cholangitis. The Lancet. 2013;382(9904):1587-99. doi: 10.1016/s0140-6736(13)60096-3.^{^[1]} Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis – a comprehensive review. J Hepatol. 2017;67(6):1298-323. Epub 2017/08/15. doi: 10.1016/j.jhep.2017.07.022. PubMed PMID: 28802875.

What is the Cause of PSC?

PSC is a complex liver disease and we don’t fully understand what causes it.

Current evidence suggests PSC is caused by a combination of multiple genetic changes in our DNA and so far unknown environmental triggers making an individual prone to immune attack ^[1]. This means that people with a particular genetic makeup may be sensitive to some sort of environmental trigger that causes their immune system to ‘attack’ their bile ducts. We’re not sure what that trigger is. It could be diet, exposure to toxins, infection, microbiota (the bugs that live inside us) or even a combination of all these factors ^[2].

There is currently more research investigating this condition than ever before, so we’re hopeful that one day we will understand the exact cause of the disease. Understanding the cause of PSC and how it develops may help scientists to define strategies to interrupt that process and treat PSC. It is possible that drugs already available for other diseases could one day be used to treat PSC ^[3]. This is called ‘drug repurposing’.

Who Gets PSC?

Anyone can get PSC, at any age, although it is a rare disease.

Watch this 15 minute video from Dr Palak Trivedi (University of Birmingham), recorded for Global PSC Awareness Day 2021.

^[1] Liaskou E, Hirschfield GM. Genetic Distinctions in Patients With Primary Sclerosing Cholangitis: Immunoglobulin G4 Elevations and HLA Risk. Gastroenterology. 2015;148(5):886-9. Epub 2015/03/26. doi: 10.1053/j.gastro.2015.03.021. PubMed PMID: 25805418.

^[2] Chung BK, Hirschfield GM. Immunogenetics in primary sclerosing cholangitis. Curr Opin Gastroenterol. 2017;33(2):93-8. Epub 2017/02/02. doi: 10.1097/MOG.0000000000000336. PubMed PMID: 28146446.

^{^[3]} Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis – a comprehensive review. J Hepatol. 2017;67(6):1298-323. Epub 2017/08/15. doi: 10.1016/j.jhep.2017.07.022. PubMed PMID: 28802875.

How many people have PSC?

According to Rare Disease UK, a rare disease is a disease that affects less than 500 people per million (or less than 1 person in 2000).

It is difficult to truly calculate how many people have PSC because of differences in health records and data collection from country to country. In the UK there could be as many as 10,500 people living with PSC but estimates vary.

The latest figures from the University of Birmingham show that PSC is indeed rare, affecting only around 80 people per million in the UK (prevalence of PSC) ^[1]. Other studies suggest it is even lower at only 56 people per million ^[2].

There is a geographic pattern of PSC with numbers decreasing from Northern Europe towards Southern Europe^[3]. A study looking at a number of different countries reported varying numbers of people with PSC in each country ranging from 0 (no one affected) to 162 cases per million people^[4].

Of course, it might also be the case that a number of individuals with colitis may also have as yet undetected PSC. In fact, studies have suggested that perhaps 8-14% of people with colitis and normal liver blood tests have changes in their bile ducts that are associated with PSC (when their bile ducts are closely examined)^[5].

^[1] Webb G RR, Marshall T, Hirschfield GM. Posters (Abstract 330 Autoimmune liver disease in the UK: a national primary care evaluation of disease geoepidemiology). The Liver Meeting; 2017/10/01. Hepatology: John Wiley & Sons, Ltd; 2017. p. 149-1185.

^[2] Liang H, Manne S, Shick J, Lissoos T, Dolin P. Incidence, prevalence, and natural history of primary sclerosing cholangitis in the United Kingdom. Medicine. 2017;96(24). doi: 10.1097/MD.0000000000007116.

^[3] Williamson KD, Chapman RW. Primary sclerosing cholangitis: a clinical update. Br Med Bull. 2015;114(1):53-64. Epub 2015/05/20. doi: 10.1093/bmb/ldv019. PubMed PMID: 25981516.

^[4] Lindkvist B, Benito de Valle M, Gullberg B, Björnsson E. Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in Sweden. Hepatology. 2010;52(2):571-7. doi: 10.1002/hep.23678.

^[5] Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, et al. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterology. 2016;151(4):660-9 e4. Epub 2016/06/28. doi: 10.1053/j.gastro.2016.06.021. PubMed PMID: 27342213.

How many people are diagnosed with PSC each year?

The number of people diagnosed with PSC each year is called the incidence of PSC. It is reported that around seven people per million get diagnosed with PSC each year in the UK^[1],^[2]. The number of new cases each year is thought to be increasing, perhaps because PSC is being diagnosed at an earlier stage or because we’re becoming more exposed to environmental triggers (or that our exposure to protective factors is decreasing)^[3].

You’re Not Alone

Joining our active Facebook group will help you to contact other people affected by PSC, ask questions and talk about living with PSC. We also host monthly live webinars and in person Information Days twice a year.

PSC affects everyone differently. It can be helpful to connect with others and hear about their experience. Many people from the PSC community have kindly shared their stories about getting diagnosed, living with PSC, managing symptoms, or, like Daniel, undergoing a liver transplant. See them all here.

Accurate Information You

Accessing the most up-to-date, accurate information is essential when you have a rare and complex disease like PSC. All of the information on www.pscsupport.org.uk is checked by PSC experts and supported by evidence and it is free and easy to access – no registration required. For a full overview explaining everything you need to know about PSC, its causes and what will happen go to: https://pscsupport.org.uk/overview-of-psc/

^[3] Ji SG, Juran BD, Mucha S, Folseraas T, Jostins L, Melum E, et al. Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease. Nat Genet. 2017;49(2):269-73. Epub 2016/12/20. doi: 10.1038/ng.3745. PubMed PMID: 27992413; PubMed Central PMCID: PMCPMC5540332.

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