Variants of PSC
PSC is a complex and varied condition with different ways of presenting itself. These different forms of PSC are called ‘subtypes’ or ‘variants’. A number of forms of PSC have been proposed because of differences between patients based on the location of bile duct damage, having inflammatory bowel disease or not, different immunology on blood testing and even risk factors for progression of the disease 6,7.
There are three well-established subtypes of PSC 8:
- Classical or large duct PSC
- Small duct PSC
- PSC with features of autoimmune hepatitis (AIH), also known as 'overlap' syndrome
Other types of PSC include:
When blockages are evident in both the large and small bile ducts of the biliary tree, the PSC is called ‘classical PSC’. If your doctor hasn’t told you what type of PSC you have, it is likely that you have classical PSC.
When blockages are only evident in the smaller, intrahepatic ducts of the biliary tree, the PSC is called ‘small duct PSC’. People with small duct PSC tend to have a milder disease which progresses more slowly and has lower risk of hepatobiliary (liver, gallbladder and bile duct) and pancreatic cancers than those with strictures in larger ducts (‘classical PSC’) 6,7.
Less than 10% of people with PSC have small duct PSC 9. It is not clear whether small duct PSC really is a PSC variant, or whether it is early stage PSC 2 because in around a fifth of people with small duct PSC, the large ducts will eventually become affected as well 1. For this reason, people with small duct PSC are monitored for any deterioration such as a sudden rise in their liver blood test results (alkaline phosphatase (ALP) or bilirubin), or sudden new symptoms) 10.
In small duct PSC where IBD is not present, other diseases will also be considered and ruled out as there are some diseases that can mimic small duct PSC e.g. primary biliary cholangitis or secondary sclerosing cholangitis which can normally be ruled out by a combination of a detailed history being taken and some blood tests 1.
In PSC with features of autoimmune hepatitis (AIH), the inappropriate immune attack seems to go further than just attacking the bile duct cells.
In this condition, in fact there also seems to be immune-mediated damage of the cells of the liver called hepatocytes 10. When this is present, doctors will often prescribe drugs to suppress the immune system, including corticosteroids.
People with PSC and features of AIH rarely develop cancers in the biliary tract, but experience a similar rate of liver disease progression compared to classical PSC 7.
Most people with PSC have inflammatory bowel disease (around 80%) which may be detected before, at the same time or after the diagnosis of PSC, or even after a patient has undergone liver transplantation. Some individuals have no evidence of inflammatory bowel disease however, this is not always clear because it is possible that these people may in fact experience very mild colitis which is simply undetectable by current techniques 11.
A recent large-scale study showed that PSC without IBD was associated with a lower risk of liver disease progression and a lower risk of developing hepatobiliary cancer than patients with ulcerative colitis 7.
If you don’t have IBD, and you’ve been diagnosed with PSC, you should expect to have a full colonoscopy with biopsies so that your bowels can be properly checked for IBD 10, which can sometime be silent (without causing any overt symptoms). The absence of any bowel symptom does not exclude the presence of IBD.
If PSC returns after you have had a liver transplant for PSC, it is called recurrent PSC (rPSC). This happens in around a quarter of people who have had a liver transplant for PSC 10, although this figure is hard to confirm, because rPSC is difficult to distinguish from the complications that can occur in the bile ducts following the transplant surgery 12.
A combination of imaging, histology (biopsies) and blood tests are used to diagnose rPSC.
Some research suggests that having a colectomy (the surgical procedure to remove all or part of your colon) before or at the time of liver transplantation may have a protective effect on the development of rPSC but there is not enough evidence at this stage to recommend this course of action 12.