New European Guidelines for the care of People with PSC
Dr Roger W Chapman is a Trustee of PSC Support and world authority on PSC. He has published 5 books, 76 book chapters and 265 original articles mainly in the field of autoimmune liver disease. In 2014, Roger was awarded a Fellowship of the American Association for the Study of Liver Diseases (AASLD). In 2015, he was awarded the Lifetime Achievement Award from British Association of the Study of the Liver (BASL) and an Honorary Life Membership of BASL. He has retired from clinical practice.
The European Association for the Study of the Liver (EASL) have just published their new guideline to help doctors caring for people with PSC. This guideline replaces the previous guideline published in 2009: I was involved in the production of the 2009 guideline as a co-author.
The process of producing guidelines is long and complicated and consists of a panel of experts in the field of PSC. In the new guidelines, the panel of eight consisted of seven European experts and one from the USA. The panel reviewed research evidence and produced a series of recommendations. Some recommendations are based on strong evidence and others on lower levels of evidence. Each recommendation was then reviewed by other stakeholders in the PSC community, including PSC Support, who proposed additional recommendations for missing topics. The proportion of stakeholders in agreement with each recommendation is given along with an assessment of the strength of the evidence (stated as the level of evidence; LoE).
The new document is 46 pages long and I have chosen to highlight the recommendations which may be of particular relevance to the members of PSC Support.
“This latest European guideline is an important document which in my opinion, discusses the latest up to date information on PSC, which in turn has provided the basis to make logical, sensible recommendations for clinicians and patients on the management of PSC in 2022.” Dr Roger Chapman, 08 September 2022.
Routine monitoring and tests
Monitoring for disease progression
EASL recommends that if you have PSC, you should be regularly monitored with:
- An appointment with your consultant at least every 12 months
- Blood tests at least every 12 months (more frequently if you have more advanced disease or are at higher risk of complications)
- Tests every 12 months to check damage to your liver, such as a Fibroscan and/or a blood test called ELF
- A scan such as an MRI scan or an ultrasound every 12 months (ultrasound scan every 6 months if you have cirrhosis of the liver; every 3 years if you have small duct PSC with stable liver tests)
- A colonoscopy every 12 months if you have inflammatory bowel disease (or every 5 years if you do not)
- A bone density scan (DEXA) every 2 to 4 years and a blood test to measure your vitamin D levels
- Additional follow-up tests if you have new/worsening symptoms or abnormalities found in your routine tests:
- Suspected bile duct cancer: further investigation with additional blood tests, MRI scan and ERCP.
- Suspected autoimmune hepatitis or medication toxicity: more blood tests and a liver biopsy may be considered.
- Suspected portal hypertension: EGD (upper gastrointestinal endoscopy), consider medication.
Monitoring for signs of cancer
EASL specifically suggests monitoring for signs of cancer of the bile duct and gallbladder at least every 12 months in people who have classical (large duct) PSC. The CA19-9 blood test is not suggested for routine monitoring.
Dr Chapman’s comments:
In my opinion the weak recommendation for yearly MRCP for everyone with large duct PSC is hard to justify on the current published evidence. Improvements in technology (such as MRCP Plus) may prove to be more useful in the early detection of cholangiocarcinoma (bile duct cancer). Currently, I would favour an approach of yearly MRCP for selected patients at higher risk.
The role of liver biopsy in adults suspected of having PSC
- EASL recommends that if PSC is suspected but a high-quality MRI scan of the bile ducts looks normal, a liver biopsy should be performed to look for small duct PSC.
- EASL recommends that a liver biopsy should be performed in people with PSC who also have features of autoimmune hepatitis.
How should adult people with PSC be monitored and treated for metabolic bone disease?
- EASL recommends that when you are diagnosed with PSC, you should have a bone density scan (DEXA). Follow-up care should be guided by existing national guidelines for osteopenia and osteoporosis.
Dr Chapman’s comments:
It important to remember that males with PSC as well as females can also develop osteoporosis.
Ursodeoxycholic acid and PSC
Should people with PSC be treated with ursodeoxycholic acid (UDCA)?
UDCA is licensed for treatment of PSC in some European countries such as France or Switzerland although currently no established drug exists for the treatment of PSC.
Based on recent research, UDCA has been reconsidered for PSC at doses up to 20 mg per kg of body weight per day, although long-term outcomes are lacking for this dose range. In a recent Japanese nationwide registry study followed 435 people with PSC. They found that UDCA treatment was significantly associated with reduced mortality or need for liver transplantation and possibly bile duct cancer.
In summary, EASL states that it is still unclear whether UDCA at moderate/medium doses has a role in slowing the progression of PSC-related liver disease , but that high doses of UDCA are harmful and must be avoided. Since the use of UDCA in PSC is widely accepted by people with PSC and treating physicians across many countries, many PSC clinical trials allow people to take part even if they are taking UDCA.
- EASL recommends that people with PSC may be given UDCA even though there is no clear evidence to confirm its benefits.
UDCA and colon cancer in PSC
Data about UDCA reducing the risk of cancer in people with PSC are conflicting. Some studies have shown that people with PSC treated with UDCA had lower rates of colon cancer or signs of colon cancer than people who didn’t take it, and others have reported no difference.
UDCA and bile duct cancer in PSC
The evidence for a potential beneficial effect of UDCA on the risk of bile duct cancer (CCA) is very limited. The larger Scandinavian and American UDCA trials did not observe any difference between UDCA- and placebo (dummy drug)-treated patients in the development of CCA. A German study followed 150 people with PSC taking UDCA over a median of 6.4 years and reported CCA in 3.3% of cases, which is about half of the expected rate. Moreover, a Scandinavian study of 255 people with PSC followed over 11 years identified a lack of UDCA treatment as a risk factor for the development of liver and biliary tract cancers.
Dr Chapman’s comments:
The treatment of patients with PSC with UDCA has been very controversial for over 20 years with no consensus amongst experts in the field. I have always been of the view that UDCA may be of benefit in a significant minority of patients with PSC, and disagreed with the recommendation in the British PSC guidelines that UDCA should not be used. Since that guideline was published, as suggested in the new guideline, there is increasing evidence that UDCA may be of benefit in some patients, and in my opinion in patients not taking part in clinical trials should be considered for treatment with UDCA.
Should people with PSC be treated with long-term antibiotics to prevent disease progression or decrease PSC-related complications?
Vancomycin is an antibiotic and is the most extensively studied antibiotic in PSC with several uncontrolled/open-label studies/case series in paediatric populations but only two Randomised Controlled Trials in adults.
- EASL does not recommend the routine, long-term use of antibiotics such as vancomycin for the treatment of PSC.
Dr Chapman’s comments:
I have previously written on this website regarding the potential benefits of vancomycin in PSC. I concluded that whilst the preliminary studies are promising, the drug cannot be recommended for adults or children with PSC until its benefit can be proven by large randomised control trials which are in progress. This opinion is in line with the recommendation above.
How should pruritus (itch) be managed in people with PSC?
Prior to the 2022 EASL guideline, recommended treatments for PSC itch included: cholestyramine, rifampicin, naltrexone, and sertraline. However, after reviewing evidence about how these medications work, the recommendations have been considerably updated.
- The 2022 EASL guidelines now recommend the following treatments for PSC itch:
- Perform endoscopic balloon dilatation (or stenting if balloon dilatation is insufficient) and take samples.
- Prescribe bezafibrate or rifampicin. If this is not effective, try naltrexone.
Dr Chapman’s comments:
I am surprised that the guideline dismisses the non-absorbable anion exchange resin, cholestyramine, in the treatment of itch in sclerosing cholangitis on the grounds that “as the evidence of benefit is limited when compared to PBC, and that of the more potent anion exchange resin colesevelam is non-existent”. This decision predisposes that the mechanism of itching in PSC is different to PBC, which in my opinion is very unlikely as itching is generic symptom of cholestasis from any cause.
It is also surprising that the guideline recommends Bezafibrate as the first line therapy for itching in PSC along with the established therapy of rifampicin although the benefits of treating both itching and having a anti-cholestatic effect on the course of PSC is potentially attractive.
New Definition of Strictures
In people with PSC, the immune system attacks the bile ducts (the tubes that deliver bile from the liver to the small intestine). This causes scarring or hardening in some areas which are known as strictures. Depending on their size, shape, location and even level of inflammation, some strictures are referred to as ‘dominant strictures’. However, the exact definition of ‘dominant stricture’ has not always been clear.
The International PSC Study Group (comprising of expert PSC researchers and clinicians from around the world) has taken steps to standardise the way strictures are described. A new term has been introduced called ‘relevant strictures’.
EASL recommends that relevant strictures should be assessed promptly and appropriate therapeutic interventions considered (such as balloon dilatation).
| Type of stricture | What this means |
| Relevant stricture | Scarring in the bile ducts that reduces the space the bile can flow through by more than 75% AND that is associated with signs or symptoms of bacterial cholangitis and/ or other problems associated with blockages.
“A high-grade biliary stricture on imaging in the common bile duct or hepatic ducts with signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.” |
| High-grade stricture | Scarring in the bile ducts (seen on an MRI scan) that reduces the space the bile can flow through by more than 75%
“A biliary stricture on MRI/MRCP with >75% reduction of duct diameter in the common bile duct or hepatic ducts.” |
Liver Transplantation
EASL now recommends that liver transplantation can be considered for people with PSC who have bile duct cancer.
In the UK, bile duct cancer has been an immediate reason to be removed from the transplant list or to be prevented from being added to the list in the first place. However, times are changing in the UK, and liver transplantation will soon be an option for some people with PSC who have bile duct cancer. Not everyone with PSC and bile duct cancer will be offered a transplant because it is only thought to be of benefit in very limited circumstances and an expert team will review each person individually to decide. PSC Support is part of the working group developing this treatment option for people with PSC in the UK.
EASL views transplantation for PSC with CCA as exploratory and recommends that such transplants are performed as research trials.
Dr Chapman’s comments:
A clinical trial for the assessment of liver transplantation for early stage CCA in PSC is in progress in the UK.
Pregnancy
- EASL suggests that people with PSC who are planning to become pregnant should be offered preconception counselling.
- If they have very damaged livers (cirrhosis), they should be closely monitored throughout pregnancy with close communication between the teams (eg liver team and antenatal team).
- EASL also recommends that oral contraceptives can be used by people with PSC (with regular liver blood tests to monitor) as long as they do not have advanced PSC.
What are the criteria and methods for screening paediatric people with PSC for inflammatory bowel disease (IBD)?
Regular colonoscopy is recommended for adults with PSC and IBD. However, in children, EASL recommends
- monitoring stool samples for faecal calprotectin, and only performing colonoscopy if the child has IBD symptoms or raised levels of faecal calprotectin.
Transition from paediatric to adult liver services
- EASL recommends that individuals moving paediatric to adult services should be coordinated and involve multidisciplinary services, sharing of information and with attention to psychosocial issues that might affect the young people.
Dr Chapman’s comments:
This is a timely and important new recommendation from EASL. The transition from paediatric to adult services has been neglected in the past and it is to be hoped that this recommendation will stimulate the setting up of efficient transition processes in the UK. It is much needed!
When should people with PSC be referred to an experienced centre in PSC care?
As a general rule, referral to an experienced PSC centre should be at the point where a patient’s management is beyond local expertise and knowledge of the responsible physician and team. In the UK many people are cared for by their local gastroenterology team when they have early disease or no symptoms, but are referred to experienced centres if the disease progresses.
EASL recommends that:
- your case should be reviewed by an expert team at the time of your diagnosis
- you should be referred to the expert team if you start to get symptoms or evolving disease.
In this way you will not only benefit from expert care, but will be considered for clinical trials looking at potential new treatments for PSC.
Dr Chapman’s comments:
I fully endorse this important strong recommendation.