Liver Transplantation in the Context of PSC
PSC Support Birmingham Meeting, 9th March 2013
Professor David Adams welcomed everyone to The Institute for Biomedical Research, University of Birmingham, which was built using a grant from the Welcome Trust about ten years ago. It’s a state of the art research centre with the top floor being the Centre for Liver Research, of which David is the Director. There is a significant amount of research currently being undertaken into the mechanisms that underlie Primary Sclerosing Cholangitis (PSC) and the development of new treatments. On the same site is the new Queen Elizabeth Hospital which is one of the largest hospitals in Europe, and that is where the Birmingham liver unit and transplant unit is based. Both clinically and research-wise, Birmingham has a long and strong affinity with PSC, and of course PSCers.
Liver Transplantation in the Context of Primary Sclerosing Cholangitis – Dr James Ferguson
Dr Ferguson gave a background to where we are in the UK with transplantation. Deaths from liver disease in the 45-65 year age group are massively on the increase in both men and women, a pattern which is not repeated in other European countries. Premature deaths from other major diseases (Heart disease and cancer) are on the decline and major progress is being made, but not in liver disease, which is reaching epidemic proportions; alcohol, obesity and viral hepatitis all have an impact on this.
The number of transplants that are undertaken each year has only increased marginally over the last ten years and the number of donors has not really increased. However, the number on the waiting list is increasing every year. There is tremendous pressure on the transplant list making the criteria for selection even more complicated.
Liver Allocation - ethics
Ethically consideration is given to equity and utility. The principle of equity is how much someone needs a transplant. For example, if someone has acute liver failure from a virus or a paracetamol overdose, and if they don’t get a transplant they are going to die straight away; they really need a transplant. This must be balanced with utility, that is, how much use the recipient will get out of the donated liver; how long that person will survive. So the person may need the liver, but if they die a week or so later, that has not been a good use of the liver. We constantly have to balance these two important concepts.
A few years ago it was agreed in Edinburgh that if there is a less than 50% chance that the person was going to survive 5 years then it wasn’t right to go ahead with that transplant. This is something that still has an influence on the decision to transplant in the UK.
UKELD is a scoring system that gives the clinicians an indication as to how severe the liver disease is. It’s based on blood tests scores from bilirubin, INR (blood clotting amount), serum creatinine (measure of kidney function) and sodium. All these are signs of how severe the liver disease is; they compile up to a score. It’s a very good predictor of which patients may die on the waiting list. The minimum UKELD score to get onto the waiting list is 49. The current average one-year mortality in the UK after a liver transplant is 9% and therefore if your chances of surviving with your own liver are better than this, then you shouldn’t be on the transplant waiting list. However, if it is worse than that, then it is reasonable for you to go onto the transplant list. This is not the only thing that is considered when making the decision, otherwise it would be a fairly simple decision to make.
Transplant lists are currently managed locally by each transplant centre. Therefore if you are on the Birmingham waiting list, and Birmingham gets an offer of an organ, Birmingham makes the decision about its allocation locally. There may be moves in the future to go towards a national allocation scheme but that hasn’t been decided as yet.
Official Indications for Transplant
What are the official indications for transplantation in a PSC patient? You could be listed if:
- UKELD is over 49
- uncontrolled cholangitis infections
- although it is unusual in a PSC patient to have ascites that can’t be controlled
- chronic confusion associated with liver disease that isn’t treated by medicines
- a rare reason and very unusual, is when the itch is so bad and cannot be controlled by medication.
Personally, James Ferguson prefers to consider transplant early; the worse thing is too late. If it is considered to late, then we don’t have time to go through the assessment process of getting someone on the transplant waiting list. Assessment is a long process and the average time on the list is around six months in Birmingham. Its better to see someone early and have the transplant team at the Queen Elizabeth Hospital say it is too early rather than it is too late.
Clinicians may consider transplant for PSC when there is evidence that:
- their liver is scarred and potentially even cirrhotic
- there is portal hypertension
- there is a large spleen
- persistent jaundice
The Assessment Process
Most people are assessed as out-patients, having a one day all over ‘body MOT’. There are many tests, and if everything is OK, the patient progresses to a second day. On the second day they will be seen by a multi-disciplinary transplant team (MDT). There is a huge education process. The MDT then discusses the case as a group to decide whether this is the right time for transplant. Consideration is given to issues including other potential treatments, timing, overall health and previous surgery. Other concerns, which may not be relevant in PSC such as non- compliance, social issues and support and malnourishment. It is important to note that the decision is never made by one person, but by the MDT as a whole.
The Waiting List
Being on the waiting list is a difficult time. Your position on the waiting list depends on your UKELD score at Birmingham, and a number of other units also do that. You are grouped by blood group and your UKELD score. Listed patients are seen every 6 weeks. It is important to remember that a transplant isn’t guaranteed because there are not enough donors at the moment to satisfy the demand. Sadly, one in five people listed for a transplant don’t receive one.
Quality: Donated organs can be of varying quality, and you do not get a choice about the type of an organ you get. In effect it is a Hobson’s Choice, as everyone wants the perfect organ, but if they waited for that there wouldn’t be many transplants done.
Donation type: DCD – donation after cardiac death and DBD – donation after brain stem death.
Split livers – sometimes part of a liver is put into an adult and part into a child. By doing this we impart a slightly greater risk to the adult, but most adults can accept that because the life of a child has been saved.
Living Donor Liver Transplant – due to the lack of donors in the UK, living relation donation is going to become more common in the future.
The Transplant Operation
James briefly explained the operation and explained how the operation differed for PSC patients. In PSC, because there is potential that the bile duct may still have PSC within it, they don’t like to create a normal anastomosis (join). In other liver transplants, the new common bile duct to old common bile duct and bladder is removed. In PSC, that doesn’t happen. The old bile duct is removed and something called a roux loop is formed. (We were shown an animation of what happens).
Immunosuppression - After the transplant people have to take immunosuppressants to help stop the body rejecting the new organ. Initially that’s three medications: Tacrolimus, Azathioprine, Prednisolone, but over time many patients will just take one.
Long term considerations
- Biliary anastomosis problems
- Slight increased risk of cancer over time due to the immunosuppressants
- Kidney problems over time due to Tacrolimus
- Recurrent PSC (rPSC) - although there are certain groups who may be more likely than others to get rPSC. About 1 in 5 people get rPSC by five years, and it only leads to loss of that liver in 10%. Urso – there is no evidence that it improves outcome, although it does improve liver tests.
Liver Transplant Outcomes
People with PSC tend to do better than the general elective population. Survival rates are far greater now than they were twenty years ago. James’ opinion was that in PSC, the 5-year survival rate is much higher than the average 75%; more like 80-85%.
James recommended that anyone who might have to go through the transplant process in the future might like to look, with their family, at the Queen Elizabeth Hospital Birmingham Liver Transplantation Patient Information Book, which explains all about transplant, warts and all.
Afterwards, Professor Adams and Dr Ferguson answered questions on PSC.
(The information stated here is based on the practices and position at Birmingham Queen Elizabeth Hospital. There may be some slight variation at other centres.)
Huge thanks to Professor Adams and Dr Ferguson for hosting our meeting and giving their valuable time freely to us once again.