Organ Transplant: Past, Present & Future
Prof. James Neuberger & Mr Simon Bramhall
Session chaired by: Prof. James Neuberger
Reporter: Dr Ali Zaatar MICR CSci
Keywords
Donation, Donor, Liver, Organ, Transplant
Organ transplant is the moving of an organ from one body to another (or from a donor site on the patient’s own body), for the purpose of replacing the recipient’s damaged or failing organ with working one from the donor site. Organ donors can be living or deceased. This was a popular session, with exchange of some teasing remarks between physician and surgeons. Professor Neuberger, a physician, chaired the session and gave the background with some humour.
History & general issues
The history of transplant was, according to Prof. Neuberger, first started by the Hindus in the 6th century BC, who did skin reconstruction. The first skin replacement was done in the 14th century by the Italian, Talia Cotsi. A slide was also presented showing the earliest transplant by the brothers Sts. Cosmas and Damian, who had become eminent for their skill in the science of medicine when they transplanted a limb from a black donor onto a white recipient.
He then skipped to the 19th century, when people started doing xenografts (ie transplanting bits of animals on to humans). This process is currently illegal in many parts of the world, but he thought that it is certainly of interest.
Transplantation in the 20th century
Following on, the emphasis shifted to the changes in the 20th century, when people started to understand the immune system, to use immunosuppression (ie, the developing of drugs that are effective in preventing rejection) and the major advances in surgical techniques over that period.
One donor can potentially provide many different organs. The liver, lung and heart are generally life-savings ones, where the alternative to transplantation is death. Other organs are life-improving, such as the kidney; where the benefits of kidney transplantation compared with dialysis and all its complications is well documented. In the 1960s, people saw the advent of kidney transplants and then heart transplants, initially conducted by the famous Christian Barnard. Other organ transplantations, such as intestine and the pancreas or islet cells, particularly in diabetes, again lead to improvement in the quality of life. Cornea transplants and skin transplants are also considered life-improving, although in patients with serious burns skin could be life-saving.
There have been about 35 hand transplants performed worldwide. There have also been two face transplants to date: one in France and one in China. The people who are good candidates for face transplants might have been deformed by burns, major surgery or trauma; for this small group of people, their quality of life can be improved enormously. Uterus transplants and ovary transplants have also been performed, but have not been very successful.
Organ donation & ethical dilemmas
He then moved to definitions, explaining briefly the difference between the deceased donors and the living donors. The latter obviously will not give hearts; they may give part of lungs, part of liver or part of kidney. For a living donor, “directed” donation involves giving your liver or part of your liver or your kidney to a specific person, whereas “non-directed” or “altruistic” donation involves giving it to anybody who needs it.
Governments in the UK and elsewhere have put a great deal of resources into promoting organ donation. However, organ donation raises many ethical issues and donation rates are still relatively low. The real problem for potential recipients is that there are not enough donated organs to go round. We have got to ration them, and how you ration a life-saving procedure raises many further questions. In such complex areas, there are rarely any absolute guides, but we need to have practical solutions.
Prof. Neuberger gave an example of an ethical dilemma, based on a real case where there were three livers donated but seven people needed them, all of whom are dying and would benefit by an equal amount from the transplant. Somebody must decide which of them get the livers, or more importantly which don’t, and possibly stand up in court or in front of the newpapers and justify the decision.
He finished by saying that transplants are certainly life-enhancing, and often life-saving, but still second rate therapy. The quality of life after transplantation is generally excellent, but still not ‘normal’ because most people require long-term immunosuppression with its inevitable consequences. Donors are in short supply, though the hope is that it will become less of a problem. However, we are unlikely to be able to fulfil the demand so rationing has got to take place, and we need a clear basis for rationing that everybody can accept and that those involved in making decisions can follow clearly.
Liver transplantation & donation logistics
After this useful background information, Professor Neuberger introduced Mr Simon Bramhall, a surgeon with particular experience in liver transplantation, but who had also transplanted other organs.
Mr Bramhall reminded us that it was in 1902 that Carol developed the basic surgical techniques for renal transplantation. The first reported renal transplant was carried out in 1933, but the recipient died 4 days later following rejection and immunological complications. However, in 1952 first living related kidney transplant was carried out; the recipient lived for 3 weeks, which was classed as a major breakthrough. Fortunately, these days our transplants last a little longer than that…
History of liver transplantation
Liver transplantation was a little later: Thomas Darzell, an American, performed liver transplants in dogs in 1962 and did his first human liver transplant in 1963. A British surgeon, Sir Roy Calne working with him, returned to the UK in 1968 and undertook the first liver transplant in the UK. However, in the first 10 years of liver transplantation in the UK the results were not brilliant: 30% of patients died on the operating table. Though the results were pretty poor, there were some advances made with immunosuppressants, specifically with ciclosporin, which was first given to humans in 1978.
In the past 30 year things have changed, and there have been some dramatic developments in liver transplantation surgeries. In the 1980s, children were being disadvantaged: there were (and still are) more children with liver disease than there are paediatric organ donors. In Germany, surgeons started to develop the first liver split, where half of a donated liver is implanted into one recipient and half into a second. Most commonly, the right lobe goes into an adult and the left lobe goes into a child. In 1988, the University of Wisconsin developed a fluid which preserved livers for longer, saving time and the rush to implant.
Surgeons in Brazil conducted the first living-donor liver transplantation in 1989. This procedure was carried out for the first time in the UK in 1994, at King’s in London.
The number of whole liver transplanted carried out in the UK has increased from 700 in 1979-89 to 5527 between 1999-2008.
Donations & shortages
There is a worldwide problem with donations, but it is acute in the UK at the moment. In the past 15 years there has been a steady decrease in the number of donors in the UK. The only way that we have managed to maintain reasonable levels of transplantation is by increasing the number of non-heart beating donors that we use. The quality of organs that one retrieves from non-heart beating donors is sub-optimal compared to that of heart-beating donors.
Over the same period, the waiting lists for solid organ transplantation have grown. In 1978, we just had 1,200 patients waiting for a kidney transplant; by the end of 2008 it was nearly 10,000. In liver transplant, there was no UK waiting list at the end of 1978 whereas we now have 350 patients waiting.
Donors really are the driving force behind transplantation, and indeed behind innovation. When we look around the rest of the world the UK is pretty poor: 2005 data showed the organ donation rate in the UK to be 12.8 per million population, roughly half the rate in countries such as France, Spain,Central Europe and the USA.
One of the things that have changed in the past 30 years in the UK is the type of donors we have; if you look back to the 1970s, we had a high proportion of road traffic accidents. Road safety was significantly improved, which led to a dramatic reduction in the number of donations by road traffic accident victims. However, we have had to extend the criteria for donors, taking on more and more patients who have had intracerebral events. In the past 20 years, the proportion of patients who with cerebrovascular accidents is much higher than it was in the first decade of this period. That means that the age of our donors is now significantly older than it was in the late 1970s, when our average donor age was around 30 years: we are now up to an average donor age in excess of 45.
Another explanation for the reduction in organ donors is the consent rate (ie, the proportion of families who agree to organ donation when they are approached by a donor transplant coordinator or an intensive care doctor or nurse). UK consent rates are under 60% while countries like Portugal, Spain and Poland have consent rates over 80%. Simon argued that it is not all about consent but also about the way we are approaching families, or perhaps portrayal by the media.
Improving UK donation rates
Surgeons have tried to find other ways to bypass the donor shortage. An alternative to cadaveric donors is using living related donors. In 2008 in the UK, the number of living donors surpassed the number of cadaveric donors. The vast majority of those were kidney donors but there was also a small increase in the number of living and related liver transplants.
The number of living related liver transplants in the US is double what it was in the early part of 2000. This has been achieved by forming an appropriate structure and by changing the legislation. They have seen a rapid increase in the number of donors that they have available.
Spain and Italy have funded transplant coordinator networks and made sure that their hospitals are saturated with people who know about organ donation and whose sole role is to convince potential donors to actually donate. This has resulted in dramatic increases in donor rates in these countries.
In the UK, Mr Bramhall said that we have terrible organisational problems and problems in procuring the organs. There are huge discrepancies across the country in the way hospitals and doctors perform. Data show that patients in some intensive care unit (ITU) cases where brain stem death is a likely diagnosis doctors do not bother to perform brain stem death tests, so these patients cannot even be considered to become organ donors.
We have differing donation rates throughout the UK. In very recent data , the organ donation rate in Newcastle was 20.6 per million population. In Birmingham, it was 11.4 per million (just below the UK average), while in Leicestershire it was only 5.2 per million.
There are also differences in terms of family refusal rates across the UK. If we can improve our family refusal rate up to the levels seen in Spain, we could achieve donation rates of over 25 per million population.
An Organ Donor Task Force (www.dh.gov.uk/en/Healthcare/Secondarycare/Transplantation/Organdonation/DH_081593) has put forward recommendations, which are in the process of being funded by Government, via NHS Blood Transfusion, who now runs the organ donation in the UK. The promise that the Task Force made was a 50% increase in donor numbers in 5 years.
Discussion
Closing the session, Simon answered questions about whether the UK would benefit from an opt-out system. He explained that there are two types of opt out systems. There is a ‘hard’ opt-out system, which works extremely well in Austria and Singapore, in which, essentially, if you die the government will take your organs. He thought that this could work in the UK, but would be illegal under current legislation. In the ‘soft’ opt out system you are expected to be an organ donor if you do not register objections, but surgeons still have to ask the family’s consent, which is barely different from the current opt-in system. The advantage of the opt-in system is that it doesn’t alienate major subsections of the population whereas trying to introduce an opt-out system would alienate, eg, the Muslims community, who would probably all opt out, whereas at the moment we go and have discussions with individual families, who sometimes give consent. In addition, it would cost many tens of millions of pounds to introduce the ‘soft’ opt-out system because it would require an enormous infrastructure, which, if introduced badly, could actually harm organ donation rates.
In conclusion, Mr Bramhall reminded us that people die every day on transplant waiting lists, while many undonated organs are being turned into ash or worm food!
Professor James Neuberger is a consultant physician and Mr Simon Bramhall is transplant surgeon, both with University Hospital Birmingham NHS Foundation Trust.
Dr Ali Zaatar MICR CSci is a Director on the ICR Board and a Senior Research and NICE implementation Manager with Northumberland, Tyne & Wear NHS Trust.
