 Introduce Giuliano Testa. Dr. Testa specializes in living donor liver transplantation for both adult and pediatric patients and is the surgical director of living donor liver transplantation at Baylor University Medical Center. Dr. Testa is world-renowned for his surgical expertise in this field. In 2018, Dr. Testa was named one of Time magazine's 100 most influential people for his work as the principal investigator on uterus transplant clinical trial. His groundbreaking work resulted in a successful functional uterine transplant and the first baby born by a uterus transplant in the US. Today, Dr. Testa will give a talk titled The Ethics of Transplanting Patients with Acute Alcoholic Peptitis. Please join me in welcoming Dr. Testa. So no matter what the 100 whatever that was, this is the highlight of what I consider my academic year. So every time I get invited by Marcus, yes, I made it this year too. There is a quipro quo in that because I invite Mark every two years in Italy. So I kind of nudge that. But I have to thank you also for allowing people like me to have a voice in front of these distinguished professors that have much greater understanding of what we do. I'm just a surgeon that tries to apply these principles to my daily life. I think I've done that much better so since I completed the fellowship. And as a disclaimer, one of the reasons why the uterus transplant program has been so successful is also because it was really founded, although some people in the room might disagree, on what I believe were a strong ethical principle. At least our ethics commission was very in favor of that. And today, we have five kids and one more next week. I think we can say something about that. But today I want to talk about something different. I want to talk about something that is very close to my daily activity and has really created a fracture in the transplant ward and has a very distinct and very visceral reaction very often. And this is the acute alcoholic hepatitis. So the idea of transplanting patients because of chronic liver disease due to alcohol is an old idea, of course. And today is common ground. But now the nucleotide in the box are the patients who are affected by acute alcoholic hepatitis, which means they practically have ingested such an amount of alcohol that have created an acute failure of the liver. Now most of them are lying in the intensive care unit and without the transplant they will die. And it's very tremendously clear to all the clinicians that no therapy means death in the great majority of patients and therapy, which in this case is only liver transplant, means survival. And to give you an idea of how intense this problem is, this is those are the curves. Not only now today the alcohol is the number one indication for liver transplantation in this country, but alcoholic hepatitis is becoming a big chunk of these patients. And I assume that most of us in this me included enjoy some form of drink. So it's a social, I would say social norm. But also I have to take position with the fact that alcohol is one of the worst in terms of self-induced damage and damage to others. In comparison to other leisure, whatever activities you may discuss. And this is unfortunately the reality in this country whereby the numbers are staggering in terms of what alcohol does. I'm not gonna read it, but those are real. And this is another thing done, but I think reputable people, Harvard School of Public Health. So those are the statistics of the numbers they have regarding college. So those are our kids the last time I checked. And the important thing is that unfortunately this thing that we see in the ICUs very often has to do with very young people. So it's a very sensitive issue. So one argument is what if we did have levers for everybody? Would be in that case, transplant everybody with acute alcoholic hepatitis. And talking around comes down probably not. There are reasons why we probably say no, even if we had unlimited number of organs and have to do probably clinical indications, some cases, or maybe have to do with the fact that we are lack of social support which seems to be a very important issue in taking care of these patients. Or maybe some people really have no clue and so why would you transplant these patients? But reality is that this scarcity is real. So that's what we live today. There is a supply and demand. And so I wanna give you an interesting twist on this. While preparing for this talk and I've had a very, I'm very ambiguous about this to the point that I apologize for some of the mistakes because I kept correcting what I was gonna say today. And so there may be some errors in the grammar in the talk. But the bottom line is I wanna say there are two fields in my opinion. And one is, I wanna put on the spot Mark Sigler. So I call those the Siglerians. And the other one I wanna put on the spot, Elisa, and Don Quir. And so I will call them Eddo Don Quir and the Gordonians or Elisians. And the reality is that Mark wrote a paper in 1991 and they're completely different opposites too. But they represent really what we feel every day in the listing committee when we have to decide who gets the liver, who doesn't get the liver. And so bottom line, Mark wrote a paper in 1991 which is a very good paper to which I have to say if Mark is the leader, I was a prosalite and that was my credo. And so the idea of the paper is that there is a moral responsibility in the self-inducing and damage to yourself. And you have to bear the responsibility. And since we have a scarcity of the organs that plays a role in the decision-making process to whom that specific liver will go. So that's really the fondness of that paper if I read it correctly. So in a few words, what it is that if there is fairness in all of this, then you have to be fair toward the one on the list who did not inflict the damage to their own liver. And they are there because they have autoimmune hepatitis, primary sclerosis, colonitis, whatever other disease we have to transplant. Although you wanna talk about justice, well, there is justice also in saying that not everybody is equal. And some people are unequal because they've been doing something that they shouldn't be doing. And the treatment falls upon the and the responsibility falls upon the patient. So this is a very characteristic view of many of us. Me included that I've had this view for a long, long time. So in a certain way, the scleria wants fairness toward the older people on the list in a certain way and demand that there is the insight and competence for the patients. And little children, there you have it. So in the other view, which we call the Gordonian would, and that's a different point. What counts is the clinical picture and not the morals behind it. And in a certain way, when we make decision, we have to focus on the clinical issues, now on why or the cause of the disease. And also we have to be beneficent. So we have to treat our patients one by one. And most importantly, I think that's a very important point for the specific of this talk. We need to be normal efficient because the moment you ask somebody to become abstinent for six months before you can activate them to transplant, you may cause some harm because that liver disease may progress or may even worsen to the point you can't transplant anymore and the patient may die. And so to this Gordonian argument, there is the Docherian, those are papers written in 2016 and 2019. So those are more recent. Maybe there's been an evolution in thinking during this time because one is 91, one is 2000. But the bottom line is that, important utility is the argument of the Gordonian is that you need to have sufficient graft and patient survival. So this is all clinical, right? And so what really make us a little dubious about this is that what number one is, what are the outcomes? And number two, what are the data? The data show that in reality, number one, if you don't get the transplant, you die in 70% of the cases. And number two is that the sleep or the relapse, which are two separate issues, occurring in very minority of the patient. So those are the data that we have. And if you wanna really have the results, those are the ones. One year survival and three year survival is no different than any other disease we transplant and the relapse are small. And if you compare the two categories of alcoholic, the one that are chronic alcoholism that are asked to be abstinent for six months and the one who are just put on the list right away because otherwise gonna die, the survival is not different. So those are the data that we have. So if the data are not different, then the allocation should be the same. And scarcity doesn't play a role in the decision that we make. And on top of that, we all know that the organs are public good. And so you need to take that in account in a certain way. And what we do the right to do is two main principle. One is to optimize the use of a scarce resource and to be fair when we allocate the resources. Those are the two principle I think we're going to apply. I'm gonna kind of keep discussing the time. I would like to have some feedback because I doubt myself. In acute, what ALF stands for in reality is for acute alcoholic hepatitis. So alcoholic liver failure. In that case, the situation is even worse or more difficult to discern because these people are not competent. Most of them are in the ICU intubated or completely unconscious. So they cannot go abstinent and they cannot give you an informed consent of any kind. And the most important thing is that if you don't do it, they're gonna die. So where do we have the hanging point? Is that relapse, number one, which is a medical entity, and the fairness, how we allocate the livers. Those are the two things. And of course, you may argue, as it was argued, that in reality, not everybody knows that it's self-inflicted in a problem on itself. I have a problem with that. To be honest, I asked myself in 2020, almost, if people really don't know, the alcohol is so bad for you, but maybe. But also it's a little tricky. The alcohol is tricky. On one side, we stigmatize the people who drink too much. On the other side, we all enjoy the little glass of wine or bourbon or whatever it is. So the way in the middle is always difficult to find in real life. So can I or can we envision a moment in which the Ciglarian and the Gordonian endocrinic can come together to a common ground and find if we can really help this patient without at the same time harming the other ones on the list? Well, you can take a very hardcore position. No one with acute alcoholic hepatitis gets a liver transplant. That means that most of them will die. Everybody gets it, which means that some people they shouldn't get it, and some more people on the list will die. They shouldn't be dying if you had access to that liver. In the reality, one little caveat I haven't told you this far is that most of these patients have such a high meld. The meld is the scoring system we use to list them. They're so high, they supersede everybody else on the list in the same region, and so they end up having excellent graph that we never see for anybody else on the list. So the idea may be we should really try to select them up front so well. They only the ideal acute alcoholic hepatitis patient end up getting the liver, maximizing the net survival of what we have. So who will be these patients? Who will be the one that have only one episode documented of acute alcoholic hepatitis? Who will be the one that have no prearsinal liver disease so they don't have cirrhosis, they have chronic liver disease? They have no history, they have a bad impact on their families or work environment or society in general, and they have a good support system. I can tell you that for whether we see, my pathologist tell me, our is a big center, on a daily census we're between five and seven acute alcoholic hepatitis in house. So this is a big deal. I can tell you about this, I cannot see any of this one that have all these characteristics at the same time. So it's very difficult to super select this patient for this form of therapy. So this is what we have but I think selection may be a proper selection and using all the help we have to make that decision is a place where we can have a common ground in trying to solve this issue that I have in myself. Now the last question I have is do we have a system in place? We need to have addiction specialist to take care of this patient. Instead we are doing this transplant in the United States without this support system which means that probably the relapse rate will be much higher than that. Can we agree between relapse and a sip? I'll give you an example. If I transplanted somebody who was an alcoholic before, it was abstinent for six months and three years after liver transplant he drinks a glass of wine. I'm not gonna judge him. That's what I drink. It doesn't mean he's gonna become an alcoholic again. So are we ready to make this distinction as a group of physician or as the public? The other thing that I have a problem with is the posture child. Every time you hear a talk about acute alcoholic hepatitis, it comes down to the mama 35 with two kids home. Well, what about the mama 35 with two kids home who's got autoimmune hepatitis or primary virus or roses? I mean those are patients too. And if you have both of them on the list at the same med score and the alcoholic one gets the liver and the other one doesn't and dies, where is the fairness? I don't know, I'm just posing these questions. And then the competence. So where does competence begin? Is only the one intubated in the ICU who's not competent or shouldn't be he or she competent before start drinking to the point of becoming stuporous and then comatose and then losing their liver? So those are the things there. At the end of the day, one irony of the case, if I'm an alcoholic I did my six months of abstinence and being pennant to all of you guys and I'm finally on the list, but my mother is 25 and an acutal colleague comes from the side and gets my liver. At the end of the day, I should be pissed because I did what the rules asked me to do and I got bypassed by the young guy on the list. So this is what I have. Thank you for your attention. Be nice, be nice. I'm gonna be very nice, Juliana. I actually just wanted to bring up a couple of facts that I think will help. The first is that most people who are alcoholics actually started drinking when they were teenagers. In fact, young teenagers, which when you get to the question of responsibility and whether we should be blaming individuals, we need to think about the fact that these are children who are the adult alcoholics. The second fact that I think we have to add is that by 2040, the main cause won't be alcoholic hepatitis, but it's gonna be Nash from obesity. And to the extent that we're gonna blame alcoholics, we're also gonna then need to blame people who are obese and people who are obese will tell you that it's both that there's a genetic component, clinical component, and we downplay the behavior component nowadays. Well, I'm not sure that you can really distinguish between obesity and alcoholism. They might have a different impact on my effectiveness at work. They might not actually. And so I just, if we're gonna start discriminating, we're gonna find out that the only people who are really quote worthy of livers are gonna be the young children. And you are absolutely right. If you talk to addiction specialists, they don't define alcohol as a moral or whatever issue. They define alcohol as a disease and they have at least this long or psychiatric disorder that may be associated with alcoholism, which is a lot of many of these patients. You're right. As a former surgeon, I have great respect for what you do. But I'm worried about this idea about what you offer. And my background as a surgeon, I did CT surgery and when I was at Stanford doing transplant fellowship back in the 1980s, we did a heart transplant. And I am a young woman in her 30s with amyloidosis and we didn't know what would happen actually. We didn't really didn't know what would happen, but she had this systemic disease and she was dying of heart failure. So we transplanted her and she got recurrent amyloidosis and died of heart failure, like I think a couple years later. I don't think it's helpful at all to moralize people with substance use disorder. I see a lot of patients in Louisville now in the opioid crisis of America right there that we're trying to palliate who is a life-limiting disease. I don't use the term addict because I think people are more than the drug that they take. But I do worry about the fact that this alcoholic person has a brain disease and that will influence the survival of his homograph that you put in. And so much like the amyloid patient which we didn't really know what would happen and I don't think anybody's doing that now. I worry about that as we think about the scarcity of resources which is just a reality. So and that would be in few words, that would be very valid if we could demonstrate and thus far we don't have that kind of data that the recidivism or the relapse of the alcohol does affect the survival of the graft or the patient. And thus far if you compare the survival long term of these patients to the one that have been transplanted for all the reasons, there is no difference. So that's the argument, that's the strongest argument that the ones in favor of transplanted this patient bring forward all the time. I'm just stating the fact, I'm not telling you that that's my position but that's what it is. Thank you. I'm afraid our time is up but we need to hear from the Siglurian. Yeah. Yeah. A year after I wrote the 1991 paper, I was on a panel with Tom Starrzel and Starrzel was incensed with that 91 paper and he had had data that he was about to publish which he published soon thereafter on 38 or 39 transplants in patients with alcoholism who had not gone through periods of abstinence. And among his patients, there were only two or three relapses of alcoholism. And in fact, he said at the panel that perhaps the ideal treatment for alcoholism is a liver transplant because there's no recidivism. I just want you to know that over the years I have moved in the Starrzel direction and particularly with regard to acute alcoholic hepatitis and I thought that your four factors to consider in distinguishing among potential recipients who had alcoholic hepatitis were quite extraordinary and very much on target. So one of the most famous transplants ever was at the University of Chicago, Christoph Brorsch. He said and he stated many times that in his opinion liver transplantation is a cathartic experience and nobody will go back to drinking after that.