Something that can predict what will happen to you is called a prognostic tool. Being able to understand what will happen in the future is important for patients, to researchers and to our doctors.
Watch Dr Thorburn discuss prognostic scoring and explain some of the techniques the PSC Clinic at the Royal Free Hospital (London) is using to develop our understanding of markers of disease progression and prediction:
Why should we predict disease progression in PSC?
In the past, prognostic tools have been limited in terms of how far ahead they can look and have only been relevant for people who already have advanced disease. Because of these limitations, researchers have unwittingly included both high and low risk patients in the same groups in research trials. This may explain the lack of proven therapies for PSC to date because research results could have found effects that were not really present or have found no effects when there really were.
Researchers need effective prognostic tools that can stratify (group) people by giving them a high or low risk score. There are a number of potential surrogate biomarkers being investigated for PSC for that purpose. A surrogate biomarker is a kind of laboratory measurement that is reasonably likely to predict an outcome (disease progression), such as death, cancer or needing a transplant and so means shorter clinical trials can be designed. PSC Support is funding the VAPoR Study, which is investigating the predictive value of VAP-1 in PSC.
Healthcare professionals would benefit from having an effective prognostic tool in their clinics to help support decisions to refer patients to larger, more experienced centres for their care.
Patients and families
People affected by PSC also want to know if they are at high or low risk of their disease progressing quickly. They want to be reassured if they are at low risk of developing complications with PSC. Equally, if an individual is at high risk, their care should be managed by the most experienced PSC doctors, and they should be referred to specialist centres very early on.
Examples of Prognostic Scoring Systems
There are a number of risk estimate scores for PSC in use or in development, including:
Mayo Risk Score
The Mayo Risk Score was one of the first non-invasive short-term (4 years) predictors of patient survival in PSC 36.
UK-PSC Risk Score (published December 2018)
- ‘Short-term UK-PSC Risk Score’ (RST) - predicts risk of complications in the short-term (two years) for an individual patient with PSC;
- Long-term UK-PSC Risk Score (RSLT) - predicts risk of complications in ten years for an individual patient with PSC 37.
Full details of the UK-PSC Risk Score were published in December 2018.
What tests are used to assess patients with PSC?
The prognostic scores use a number of elements to build up a picture of factors that may affect whether the disease is likely to progress. These elements are often tests used in clinic to assess how you are doing and if your PSC is progressing.
Clinical details and demographics
We know from a large international PSC study published in 2017 7 that certain factors are likely to affect disease progression; specifically, gender, the age at which PSC is diagnosed, the 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. Your doctor will consider these factors when assessing you.
A number of factors that may be related to disease progression can be measured in the blood, such as:
- Alkaline phosphatase - ALP that is less than 1.5 times upper limit of the normal range is associated with a better outcome and a reduced risk of bile duct cancer in PSC 40.
- Platelets – a low level is associated with a worse outcome.
- The fibrosis marker PRO-C3 predicts transplant-free survival in PSC 41.
- ELF (Enhanced Liver Fibrosis) Test 42,43.
- Using three fibrosis markers expressed during early stages of fibrosis, the ELF test predicts transplant-free survival in PSC – the higher the score, the worse the disease outcome.
UK-PSC collects and stores blood (and other biological samples) from people with PSC for use in PSC research. Thanks to the many PSC patients in the UK who have given samples to UK-PSC, we have learned a great deal and landmark research has been published 7,37.
Some hospitals also have their own PSC research programmes, so you may be asked if you’ll provide a sample more than once. It all helps!
- Fibroscan (transient elastography) - measures liver stiffness (fibrosis).
- Ultrasound and shear wave elastography, which is a special, advanced kind of ultrasound (also measures spleen stiffness).
- 2D-Shear Wave Elastography - gives a more detailed assessment over a larger area of the liver.
- MRCP/MRI with contrast
- Contrast enhanced ultrasound
If you are seen in a hospital that conducts PSC research, expect to be asked for biological samples and to undergo additional tests. Some of these studies may be working towards investigating potential surrogate biomarkers and non-invasive methods of assessing disease progression, or be collecting on behalf of UK-PSC.
Benefits of prognostic tools
This work is positive for all patients, their family/carers and their healthcare providers. Effective prognostic tools will help in the development of new treatments for PSC as well as improve patient care and the timing of referral to specialist centres if PSC starts to progress in some people.