Minerva Research Group - Interviews with the Experts
As part of our ‘Interviews with the Experts Series’ we are publishing our conversations with some of the leading experts in organ donation and transplantation. Through these interviews, we want to shed light on the various issues in the field. We begin with discussing the issue of liver disease and liver transplantation.
Interview with Professor James Neuberger on 2nd May 2022
Dr Farrah Raza: Hello Professor Neuberger, thank you for agreeing to being interviewed today. Can you please tell us about your professional background?
Professor James Neuberger: I trained at Oxford and have worked in liver disease for getting onto fifty years. I’ve seen transplantation develop from its early days and seen it become a routine procedure. I’ve also worked with the liver unit in Birmingham for many years, I’ve also worked for NHS Blood and Transplant. I was associate medical director for organ donation and transplantation. I’ve been an editor for the journal Transplantation, I have published a number of books and many journal articles about organ donation, transplantation and liver disease in general.
Dr Raza: The main causes of liver diseases are well known and yet liver disease is on the rise. What can be done to prevent liver disease and the need for transplantation?
Professor Neuberger: In western countries the two main causes of liver disease are alcohol and fatty liver disease or metabolic liver disease which is associated with diabetes and obesity in particular. There are many other causes of liver disease. In particular viral hepatitis, whereas hepatitis B and hepatitis C are becoming less common now – hepatitis B because of mass vaccination programmes and hepatitis C because of effective cures. There are many other causes, in particular autoimmune disease, genetic diseases and inherited disease and so. But by far in a way the largest causes are fatty liver disease and alcohol.
Dr. Raza: So, what can be done to prevent liver disease?
Professor Neuberger: The alcohol one is very difficult, because alcohol is very much engraved in many different cultures, it’s a social activity, people enjoy it and public health measures are focused primarily on education, information and also fiscal approaches. So, alcohol is quite heavily taxed and a number of studies around the world have shown that minimum pricing, so that a unit of alcohol costs maybe one Euro, two Euros, whatever, will reduce the deaths due to alcoholic liver disease. And a number of countries now increasingly are introducing minimum unit pricing and although there’s been quite a lot of opposition to this – primarily from the industry – there does seem to be a good association between the cost of alcohol and the deaths from alcohol related liver disease.
Obesity again, is another problem, it’s well established. We are seeing all around the world increasing rates of obesity. That in itself can lead to fatty liver disease, cirrhosis, liver cancer, liver failure but also diabetes that can further exacerbate a fatty liver and again it’s public health measures I think again to be the most effective: information, encouraging people to make the right decisions perhaps by taxing high sugar content drinks for example. But essentially, it’s public health information encouraging people, making it easier for people to make the right decisions I think again to be the key ways in which we can tackle these two major problems.
Other conditions, the genetic ones, the autoimmune ones, the metabolic ones, earlier recognition, earlier treatment will significantly prevent the development to cirrhosis. The two main issues are excess alcohol and fatty liver and it is public health measures that are going to be the most effective but they are also the most challenging.
Dr Raza: And what is unique about the liver as an organ?
Professor Neuberger: Let’s say unlike the kidneys you only have liver, the liver has a tremendous number of functions, it acts as a powerhouse, it serves as a reservoir for some vitamins, iron and other material, it metabolises many chemicals – some natural, some ingested – it metabolises drugs, it regulates hormonal activity, it produces a lot of the proteins for example, for blood clotting. So, it has a very large number of functions. It’s a very robust organ. So, if you have a normal healthy liver. you can remove half that liver and the remainder will regrow and recover. So, if for example you have a tumor in the liver you need to remove half or if you wanted to donate part your liver then the normal liver will regenerate. That’s not true with cirrhotic liver, a damaged liver will not regenerate normally. So, that’s the other major feature of the liver and that third factor has kept me in business for the last fifty years or so. So, I owe it a lot and as I think there are two quotes I have about the liver, one I think was Woody Allen, “The liver is my second favourite organ”. So, it’s a very important single organ that has many different functions to maintain health.
Dr Raza: Okay, thank you, that’s very interesting. Social and ethical dilemmas in the field continue to persist and these include stigma arising from alcohol and obesity. Could you perhaps offer your views on one or two of these issues?
Professor Neuberger: Yes, I think particularly with alcohol people have become very judgmental and as we have learned more about alcohol and alcohol dependence, I think people should become more understanding. Alcoholism – it’s not a term we use now – but alcohol use disorders and people abuse alcohol for many, many reasons. Some are loneliness, depression, sadness, social integration, enjoyment and one doesn’t want to demonise alcohol because many people drink alcohol, they control it and they enjoy it. But some people do become dependent and getting the dependency has many different factors. We know the environmental factors are important, we know that genetic factors are important, we know that the time, the amount of alcohol that you drink as you drink more the chances of becoming alcohol dependent increase. And for people who drink alcohol to excess it’s a miserable existence and the majority are not proud of it. Their life is miserable and that further exacerbates their drinking habits. So, their treatment is difficult from a simple medication/ treatment, it’s not that effective, there are a number of drugs that can help to reduce the dependence. But essentially people need to be helped to come off alcohol, to stop becoming dependent on alcohol and again depending on the reasons why people do abuse alcohol, the approach is going to be different.
But people are really judgmental and it’s the same with obesity. The majority of people who are overweight don’t do it out of choice. Most of them, not all, would much rather be thinner and it becomes another disorder that requires help, support and understanding not judgement and criticism.
Dr. Raza.: In your clinical experience what are the specific challenges in the field of transplantation and more specifically liver transplantation?
Professor Neuberger: I think there are many challenges. I think perhaps the most important thing is to focus on removing the need for transplantation. So, that people don’t develop end stage liver disease and they don’t need a transplant. That’s the optimum but we’re a long way from that. The mortality from liver disease is rising in the UK, European countries and North America not falling. The challenges partly with organ donation: we don’t have enough donor organs to meet the need. This leads to several problems. It leads to rationing and again there are many ethical, moral and legal challenges to how you allocate a limited live saving resource.
The other thing that it leads to is unethical practice with people being forced or sometimes enticed to sell their organs or part of their organs and we have cases where executed prisoners are forced to become organ donors. So, it leads to unethical practices as well. So, I think donation, how to increase donation in an ethical way. There are many ethical debates for example, if you are not prepared to donate an organ should you get priority for receipt of an organ. Some countries, Singapore, Israel for example, have said they can give priority to those who prepared to donate an organ therefore they also have priority to receive. Is that ethical, you can argue both ways. If you have a limited supply, how do you decide who gets an organ. Does a child have priority over an adult? Does say a mother with five children who is dying get preference over a convicted sex molester for example who is in prison? Does somebody who has a so called self-induced certain alcohol or indeed fatty liver disease should they get less priority than somebody who has got liver disease and liver failure to no fault of their own? So, both on the donor side and the recipient, the allocation side there are challenges to make sure the system is equitable, transparent, fair, balances need and justice. And people around the world are trying to balance these competing demands on a limited system. So, the solution if you can’t get, if you can’t prevent, the need for organ transplantation is to increase the number of donors. We are still burying or burning a huge number of organs that could be used to save lives and that to me is a terrible thing.
We’re seeing now the development of xenotransplants, the use of organs from animals, mainly genetically modified pigs, we’ve seen the first heart transplant which was successful for a few months (the recipient died), more recently we’ve seen a pig kidney being transplanted into a brain-dead recipient to show proof of concept. I think there are many hurdles, there are many ethical and medical issues. So, xenotransplant may be a solution in the future, I think it’s still a few years off. But I think certainly for some organs there’s another way of helping the organ donor shortage.
Dr Raza: In terms of the law and regulation of liver transplant what would you change?
Professor Neuberger: In terms of the legal side, I think the legal side is not a major problem. You do need to operate in the legal framework and how far the law is influenced by ethics and how far the other way around I think is debatable. Most of the areas of transplantation are enshrined in law. I think they are some areas in some countries where the law is unnecessarily intrusive, for example, whether you can use HIV positive donors for HIV positive or negative recipients, that’s sometimes controlled by law. But in a democracy where the rule of law is considered essential as in most countries in Western Europe, North America and so on, I think the law is constructive in this area. I think the main thing is to change the perceptions of people, say that many more are supportive of organ donation. We still see particular amongst some ethnic groups a reluctance to support organ donation and this is the area that you can’t control by legal. But I’m sure you can make organ donation non-dependent on … consent in the same way as if the law orders suppose an autopsy, you can’t overrule that. But I think that would be wrong and I think more importantly say that the law makers.
So, I don’t think that the law on the whole is the major issue, its people’s perceptions. The only area where perhaps the law will need to be reviewed is with xenotransplant, which in some countries is still illegal.
Dr Raza: What is the one thing that you would like patients and the public to consider when thinking about the topic of liver transplant either from a public health viewpoint and/or from their own personal viewpoint?
Professor Neuberger: I would like everybody to consider whether they in the event of their death they wish to be an organ donor. A lot of people don’t like considering their death, many people haven’t made their wills for example. So, I think people need to consider what is right for them and let their families know what their wishes are in the event of their dying in circumstances where organ donation can take place. It’s important to remember that only a small proportion of those who die, die in a situation where organ donation can take place. And for what it’s worth we know from the own/our own experience in the UK of the organ donor register, those on the organ donor register actually live longer than those who are not on the register. And finally, I would say that families who have agreed to organ donation have a far better outcome in terms of bereavement processes. It’s still awful for them but many donor families get enormous pride and benefit from knowing that out of their tragedy has come life and good life for several other people. So, I think that’s what I’d like people to know that organ donation is not only good for the recipients but it’s good for their families. So please consider it and let your family know what your wishes are.
Dr Raza: And finally, could you kindly outline future challenges in transplantation, just perhaps one or two examples.
Professor Neuberger: Xenotransplantation is a challenge and I think you’ve not only got the immunological challenges that – obviously pig hearts are designed for pigs and not humans – you’ve also got the physiology to be considered that for example the lungs in the pig, the pig spends most of its live horizontal and therefore the blood flow and oxygen exchange is done in a certain way, that will be slightly different for humans who spent a lot of their time upright as well as horizontal. The pig liver for example, and to a lesser extent, the kidney and the lungs also make a number of proteins. So, the pig will make pig albumin, pig clotting factors, pig growth hormones and so and how effective those pig proteins will be is not yet certain. So, I think the physiology issues we considered. People were concerned about infections but I think those fears probably have not been realised. In particular, there were the so-called pig endogenous retroviruses – a group of viruses similar to the HIV – and people were concerned that these might well get into the human population and cause disease and that’s still a worry. The pig does seem to be a really good source of animal organs. Ethically people have concerns but after all we use … and other human/ other pig products to safe lives. Well, we used to use pig insulin in everyday practice to control diabetes So, there are those issues, that’s one.
And I think the major one is how you best allocate your organs: waiting time need, utility, benefit, justice, equity. What are the criteria that should be used? The other issue is getting more people to donate, working at why they’re so reluctant to donate and seeing how best to show that their fears are unfounded, let them have confidence in the system and as I said in the event of their death safe more lives.
Dr Raza: Thank you so much Professor Neuberger for the interview and your time.