I'm here to present the case that they will reflect upon. This is a case of a 44-year-old man admitted to the hospital with jaundice. He started drinking alcohol at age 16. He drank up to a bottle of wine a day with occasional beers for up to eight years, and he reduced his alcohol intake over the last 10 years to two to five beers per day. He has one conviction for driving under the influence of alcohol six years ago, and he completed an alcohol treatment program four years prior to his hospitalization. He continued to drink alcohol until three weeks prior to the onset of jaundice, malaise, and fatigue. Upon admission to the hospital, his labs included an INR of 2.1, sodium of 136, total billy of 33.2 milligrams per deciliter, creatinine of 1.0, and his treatment and hospital costs, of course, are summarized here. He was started on prednisone, 40 milligrams per day. His day six Leo score was 0.68, which is consistent with a poor steroid response, and his prednisolone was discontinued. His latest MELD NA score is 29, and his creatinine is now 1.7 milligrams per deciliter, and he has variants in the PNPLA3 gene. Michael? Well, thank you very much, Scott, and thank you to the organizers for this opportunity to talk about this patient. So they are my disclosures. So I'm going to address one or two particular discussion points today, and the first is to emphasize that this patient has two rather than one disorders. He's two parallel disorders, which act together to affect his prognosis and our understanding of what's happening to him and our management, and then I want to address what we're trying to achieve, and we're trying to achieve something more than survival, so we're trying to restore this patient to a healthy quality of life, but we also have to recognize the limits of what we can do, and that brings in an understanding of futility, and hanging over the whole case is the question of whether this patient should receive a liver transplant. So I mentioned that this patient has two diseases, alcohol use disorder and alcohol-related or alcohol-associated liver disease, and the prognosis of this patient is dependent on each. Relapse of his alcohol use disorder will accelerate his ALD and harm his likelihood of survival, whereas treatment of his alcohol use disorder potentially benefits both his AUD but also potentially benefits his liver, and the prognosis without liver transplantation differs from the prognosis with liver transplantation, and when we consider what might happen without liver transplantation, we have to consider what would be a futile outcome for him and where liver transplantation has no hope. So recently, the ASLD Guidelines Committee commissioned a group for a new guidance. It's a guidance rather than a guideline because of the quality of the data don't meet the requirements to be called a guideline, and both Yonji and I were on this. David Crabb was the senior author of the paper, and Jean Im and Jessica Mellinger were our colleagues in the writing committee, and we have some comments to make in that guidance that refer to this sort of patient, the patient we're describing, and I'll just address them here. So the first is that referral to professionals in the treatment of alcohol use disorder is recommended for patients with alcohol-related liver disease in order to ensure access to a full range of alcohol use disorder treatment options, and while I won't review the data here, the norm is for these patients not to get any form of formal treatment of alcohol use disorder, and the norm is for them not to get recognized often. I see it, the earlier mention of the electronic medical record, which I raised my hand, I just want to, if any of the executives from the University of Wisconsin Health System are here, I raised my hand when they asked who was in favor of the EPIC system, home in Verona, Wisconsin. But one of its main points is the problem list, and so I often see a patient with alcohol-related or associated liver disease, and in their problem list there's no mention of their, that they have potentially an alcohol use disorder. So it's unrecognized. And to get it recognized and then to get it treated, there are experts in this, we should recognize how well we benefit from having them help us. Then multidisciplinary integrated management of alcohol-associated liver disease and AUD is recommended, and that integration is one of the changes that's happening now. So the programs that are moving forward are finding ways of integrating alcohol addiction specialists into the liver program. And then the goal is to improve abstinence. And then there are limited data, but there are pharmacotherapies which can be considered, and we have limited experience ourselves. We need help with those. I'd also like just to consider the issue of survival benefits. This is often spoken of in terms of liver transplantation, and I acknowledge the role of Bob Marion, who's at this meeting, and Doug Schaubel at the University of Michigan in bringing this to the attention of the transplant community. But the key to this is that it sees the survival from the time that you are seeing the patient or in transplantation, often from the point of placing the patient on the transplant list, as being what the patient recognized. We used to consider survival after transplantation and really ignore the interval before transplantation. But if you're going to consider the outcome for these patients, it's the continuum before, during, and after. And for patients with alcohol use disorder and alcohol-related liver disease, there may be recovery in the pre-transplant period. So it's not just deterioration. There's also potential recovery, which makes prognosis prediction very difficult. And I mentioned we're interested in survival, but more than survival. So health is more than an absence of disease. It has many dimensions, and it goes into the notion of well-being. And that's what we're trying to restore these patients to. Now how do we predict what's going to happen to alcohol use disorder? And you can see we have many scoring systems indicating that we have none that is very good. And the first is this one from Michigan by Thomas Beresford. It was when I was there. But it identifies various domains that make it more or less likely that a patient will abstain. So the isolated patient is more likely to return to drinking. The integrated patient with employment, a family, a home, more likely to abstain. The patient who doesn't recognize they have an addiction is not going to be as likely to abstain. The patient who has had many failed rehabilitation attempts, and the patient we have just heard about has already had a failed rehabilitation attempt. Patients with underlying psychiatric disease, particularly disorders of personality are at risk. This just goes to show that in the case we have heard, we don't really have enough information to really predict what's likely to happen. But there are more simplified systems. This is the high-risk alcoholism relapse scale. It came from veterans. It's unrelated to transplantation, but it looks at who is likely to drink again. And it had three components, heavy drinking, daily number of drinks, and prior treatment. So it's already overlapping a little bit with the Beresford model. And a score of three, and abstinence less than six months in a big study, were independently associated with significant risk of relapse after transplantation. And this is one that has just come from the Accelerate group, just in patients with alcoholic hepatitis, showing degree of drinking, prior failed rehabilitation attempts, and legal problems may predict. And this patient has had a DUI. However, when you apply these scores to this patient, you see that both the first and the second do not really tell you whether the patient is going to drink again. In fact, he falls below the level of high risk in both of them. And this is part of the truth of this story, is that it's hard to predict these patients, because you're dealing with something that's very nuanced when you're dealing with the assessment of risk of return to alcohol use. A more comprehensive model is the Stanford Integrated Psychosocial Assessment for Transplant, or PSIPAT. Many transplant programs are using that. We had a poster today about it in the Wisconsin program. But once again, it really just tells you the patient is more or less likely to be able to survive well after a transplant. So while we have the goal of abstinence, and we have the goal of living better, our ability to actually tell what's going to happen in the future is quite limited. Now, this is a model for looking at futility, which I like very much. It's from Jennifer Lai, who's at this meeting. I spoke to her a few minutes ago. And she identified two aspects to determining futility. Those aspects of the patient's care and vulnerability that are likely to respond to transplant, and those that are not. And you can see on my left here, the patient with the large candidate A has a high pre-transplant vulnerability, but most of it will respond to the transplant, whereas the patient on the right-hand side, most of it won't. And the question for us is, with this patient we're discussing, is his risk of relapse after transplantation, is it a transplant non-responsive risk, or a transplant responsive risk? Finally, there's the question of agreement. Who agrees to transplant this patient? And this is the model from Lill. And it has four components. Many of you in the audience will be familiar with this. The medical team, the specialists in addiction, the senior hepatologists, and the surgeons and anesthetists. And in this model, everyone needs to agree. Also the patient had to have their first episode of acute alcoholic hepatitis, and they had to have good social support. But it goes to speak to one of the other aspects of whether this patient in our group would be a transplant candidate. In addition to having difficulty to predicting his outcome, we have also difficulty of agreeing with each other whether we should transplant him. And so we need better data on how to achieve this sort of decision making in the best interest of the patient. So what does the guidance say? It says patients with decompensated alcohol associated cirrhosis should be referred for consideration for liver transplantation. And it makes a change from the previous guideline, which says that candidate selection should not solely be based on a fixed interval of abstinence. So it's calling on us to have a more nuanced assessment. While I have just told you we have difficulty making that nuanced assessment. And finally it says there are some patients who may be considered carefully selected patients with favorable psychosocial profiles who would be suitable for transplantation if they did not respond to treatment. And we know this patient has not responded to treatment. So here are my takeaway points. The first is that this patient has two parallel disorders which together affect his prognosis. The second is that integration of alcohol use disorder management into the medical team enhances care. And that's something we should go back to our centers and try to work for. And that we should consider measuring beyond survival so that we're restoring psychological health. But that predicting future drinking is an inexact art. And scoring systems offer guidance but not thresholds. And finally that the selection process for liver transplantation should be multidisciplinary and seek consensus through dialogue. So I'll stop at that point. Thank you very much.

alcohol-related liver disease

alcohol use disorder

alcohol abuse

liver transplantation

multidisciplinary approach