Thanks very much, George, and I'm going to present a new guidance on alcohol-associated liver disease. Each of the previous two speakers has started by calling your attention to the distinction between a guideline and a guidance, so I don't need to do that, but I can put it in context, a historical context, that if Moses came back with his tablets of stone now in this era of guidances, they would be called the Ten Suggestions. And so that's where we're similarly giving you some suggestions about managing alcohol-associated liver disease. You can see the co-authors on this guidance were led by David Crabb, and then Jean Im, Yonji Zabo, Jessica Malinger, and myself. Like the previous two guidances, this is following a previous guideline published in 2010 by Drs. O'Shea, Darasathi, and Art McCulloch, and that was a very successful guideline. When we came to the conclusion of our guidance, I looked up the previous guideline on Google Scholar, and it had over 1,400 citations. So why do we feel the need to provide a renewed guidance now? And it is because I think there's a culture change going on regarding the view of alcohol-related liver disease within the hepatology community and the transplant community. And we want this new guidance to reflect that culture change. It's very evident at this meeting, actually. And it starts with nomenclature and the use of words. The terminology we're using has changed. And so just as Keith Linder was talking about primary biliary cholangitis, and the change from primary biliary cirrhosis came largely, I think, about because of the reaction of patients and their families to the term with cirrhosis, which they felt was stigmatizing. But similarly, the term alcoholic is a stigmatizing term. And so we're trying to avoid that. We're finding it difficult, though, because some of the terms just are difficult to just get around. And we're replacing it with alcohol-associated or alcohol-related. We're not calling these patients alcoholics. A drink can be alcoholic, but a person can't be alcoholic. But they are persons with alcohol use disorder. And so cirrhosis due to alcohol-related liver disease. However, we get into a little bit of a problem with alcoholic hepatitis, which is sort of a well-fixed term, and it's a bit of a jawbreaker to say alcohol-associated hepatitis. But I suspect we're even going to go there. And the other part of the culture change really is the recognition of the role of alcohol use disorder in the life sequence of patients with alcohol-related liver disease. So previously, we used to concentrate on the liver disease, and we recognized the importance of comorbid conditions and increasingly of genetics, but there was long-term interest within this association in metabolism of alcohol and how it affected the presentation and origin of alcohol-associated liver disease. But there was less consideration of the underlying alcohol use disorder. And that is now changing. So our new guidance tries to take that into account. And to do that, we've had to become more familiar with how addiction specialists understand alcohol use disorder. And the place we start is by understanding their language. And so I'll just give you a little example of that. So what are the terms that are in common use? Here we have craving, which is a strong subjective drive to use a substance. That's common to many forms of addiction. A slip and a relapse are different from the idea of you're drinking or non-drinking. Previously, we had a very binary view of drinking. You're either drinking or non-drinking. Now we see a slip is consumption of a limited amount of alcohol, followed by an immediate attempt by the person to reestablish abstinence, whereas a relapse is to return to harmful drinking. And even the term harmful drinking or addictive drinking gets the notion that there may be qualitative differences in drinking. So in the field of addiction medicine, a result, a beneficial outcome, is often improvement in the harm, sometimes called harm reduction. Whereas particularly in the world of transplantation, we have seen the only outcome that is worthy of consideration is abstinence. Abstinence remains the goal, but in a condition which is a chronic condition with relapses and remissions, it's a goal that many patients have difficulty achieving. And our new guidance, we hope, takes into account that understanding. And loss of control is drinking more than you intend or the inability to stop once begun. And you won't see the word recidivism in the guidance because, as I mentioned, we're doing our best to avoid terms that are moralistic or stigmatizing. And recidivism, in its tightest definition, is a return to an illegal activity. And this is a legal activity. So I've just one epidemiology slide. It's related to the United States because this is an ASLD guidance, but I recognize you could draw this out to a worldwide view and get very similar views. Alcohol is the source of half of all cirrhosis in the world. So 136 million Americans aged 18 drink alcohol, 18 or older drink alcohol, 17 million have alcohol abuse or dependence in the older term. Now we would say they have alcohol use disorder. And excessive alcohol consumption is the third leading cause of preventable death. And because it affects persons younger in life, its impact on the potential years of life that are lost is greater than those diseases which are associated with age and degeneration, such as stroke and myocardial infarction and many forms of cancer. So the average number of years lost for a death due to alcohol-related cirrhosis is 30. And alcohol-associated cirrhosis causes 35,000 deaths a year. So even though the number of patients with alcohol-associated cirrhosis undergoing liver transplantation is rising, it is dwarfed by the number of deaths that are occurring in our community. But it is now the most common indication for liver transplantation. You saw Julie also said HCC is the most common, but that's because it includes some people with alcohol-related cirrhosis who have HCC. So if you just take alcohol-associated liver disease as your primary diagnosis or secondary diagnosis, it will come out as number one. It's being chased by NASH, and it's a question of which one is going to be number one or number two at any one time. But the comorbidities of metabolic syndrome have up to now excluded many of the potential NASH patients. And it's changing at a different rate in different age groups. And this is a very nice paper by Elliot Tapper and Nihar Parikh from the University of Michigan. And they show that the deaths due to alcohol use disorder or deaths due to alcohol-related liver disease or cirrhosis overall are rising in many age groups. But the greatest increase is occurring in 25 to 34-year-olds. So this is a scourge that's having a disproportionate effect on younger people. So what did we say in the guidance? Well, we first of all came to the point of making alcohol use disorder a focus of the guidance. And alcohol use disorder is often hidden on account of stigma and shame. And the key is to recognize excessive drinking. And that starts with taking a drinking history. And we are all guilty of this, of seeing patients and not taking a drinking history. But this stretches out into primary care, emergency rooms, et cetera. And then most patients with alcohol-related liver disease have had several previous contacts with medical professions at which their drinking disorder is not recognized. And so how do we recognize this? Well, we can structuralize that. This can be done through the electronic medical record with what's called SBIRT, screening, brief intervention, which can be as brief as saying, do you realize you have an alcohol problem? Do you know where to get help? And help is referral for treatment. And I looked in our own electronic medical record on a patient only last week. So this is the wonderful EPIC system, which comes from Verona, Wisconsin, which we have brought as a gift to you. And we had SBIRT in the system. But this patient had the SBIRT tab and no answers in it. So it goes back to the thing that you have to ask the question. If you don't do that, it doesn't work. So here is a simple set of questions that you can ask, also called Audit C. And I'd recommend, for those of you who are intrigued by what I'm saying today, to go to the NIAAA website. It's full of excellent information, simple to apply, about how you can improve your ability to identify patients with problems with drinking. But the three questions, there's a scoring system. So if you're a little bit more particular, you can actually get a score. But they are, how often, it relates to the last 12 months. How often in the last 12 months did you have a drink of any kind? And if you say yes to that, how many alcoholic drinks did you have on a typical day when you drank? And how often did you have five or more drinks on any one occasion? So this doesn't answer the question, does the patient have an alcohol use disorder of what kind, et cetera. It just tells you, this is a person that I need to take a better history, a more detailed history. And so that's screening. And then if you find the patient, brief intervention. You can be the source of brief intervention, and then referral for treatment. So here's what we say in the guidelines. Gastroenterology, hepatology outpatient clinics, visit to primary care or emergency departments, and inpatient admissions should be seen as an opportunity for screening for alcohol use using validated questionnaires. So this is not in the previous guidance, because we didn't have that previous focus. And then brief intervention, pharmacotherapy, and referral to treatment should be offered to patients engaged in hazardous drinking. And this is a way to define it, using either Audit C or the more complete audit. Or you identify binge drinking. And finally, alcohol biomarkers can be used in the aid to diagnosis and support for recovery. And these include urine and hair ethylglucuronide, urine ethyl sulfate, and phosphatidyl ethanol in whole blood, which are not affected by liver disease and therefore preferable. Now one of the things that I've been at several meetings, including an early morning breakfast session this morning, and one of the things that came out is, not only are we as hepatologists not well versed or trained in this, but also many people have difficulty finding the expertise. So one area that I think, for those of you in the audience who are influential at education of medical residents, surgical residents, fellows, nurse practitioners, would be to include treatment training and identification training and addiction in the curricula that you are expecting your trainees to take. And the second thing here is that referral to alcohol use disorder treatment professionals is recommended for patients with alcohol-associated liver disease. In order to ensure access to a full range of treatments. So that is a recognition that there is a whole area of expertise other than ourselves. And we should try to find those experts and link with them. And multidisciplinary integrated management of alcohol-associated liver disease and alcohol use disorder is recommended. And improved rates of alcohol abstinence is achieved with these maneuvers. That is the way the world is going. The challenges are who's going to pay for it. The guidance doesn't offer you answers on that. But if you can form a real bond with the addiction specialists in your center and have them integrated into your hepatology groups and your transplant group, you will have a different outcome. And finally, based on limited data, pharmacotherapy is available. Acamprosate and Baclofen, we mentioned. Acamprosate is approved by the FDA for this indication. Baclofen is not. And there really is a dearth of good studies of both talking treatments but also pharmacotherapy in the area of alcohol use disorder in patients with liver disease. That's an absolute need. So I'm now going to come to the issue of alcoholic hepatitis. And alcoholic hepatitis is a challenging area because, again, it has problems of definition. But fortunately, in 2016, the NIAAA brought together a group of experts. And because I was there, I'm going to say so-called experts. But we were brought together to Bethesda. And the real question was, how can we improve treatment studies in the area of alcohol use disorder and ALD? And we immediately saw that one of the problems was there's a difference in practice in Europe and in the United States and Great Britain on the other side. And it was regarding to the use of liver biopsy in the diagnosis of patients with alcoholic hepatitis. And alcoholic hepatitis has a histopathological correlate, alcoholic steatohepatitis. And so in the studies from France, from Spain, from the Franco-Belgian studies in transplantation in alcoholic hepatitis, every patient has been defined as having alcoholic steatohepatitis as an entry criterion to the study. And that's not the way we practice here. And this was what we came up. And I think this diagram, which is in the guidance, is a nice way to look at it. There are patients in whom we think have definite alcoholic hepatitis because they have alcoholic hepatitis and an associated histological diagnosis. And then there are patients who have a clear cut clinical condition, which we think is alcoholic hepatitis. And in those patients, requiring a biopsy is not necessary for entry into a clinical trial. But in clinical practice, the same would be true. And then there are patients who have a confused picture. Is this due to alcohol or is it not? And are you going to treat it or are you not? And there, a biopsy is a good idea if you can manage it. So the statement here says, the diagnosis of alcoholic hepatitis, definite, probable or possible, should be made using the published consensus criteria. And the consensus criteria, as I said, are these NIAAA criteria. And then there are prognostic scores for alcoholic hepatitis. And we have four, but I've only picked these four. There are more than four. And there is a wonderful statement by a character in one of the plays by Chekhov. And Chekhov, as many of you, if not all of you know, was both a practicing doctor as well as a writer. And he often puts doctors into his plays. And they're very often a sort of dull stick. But in this one, this doctor said, where there are many treatments, there is no cure. And the same could be true of prognostic scores. Where there are many, they all work fairly well but not great. But so you have all these here. The most famous, because of time, is the Madry discriminant function. I was happy to see that Dr. Willis Madry was hale and hearty at yesterday's reception. So he is still going strong. And so is his discriminant function. And it predicts 30-day mortality in alcoholic hepatitis and offers you a link as to when to start corticosteroids if you believe in them. Recently, a new area of interest has been those patients who have a discriminant function less than 32 but still are sick. And these are now being called moderate alcoholic hepatitis. And an area of future research will be looking at those patients because they still have a mortality even though it's not as high as the people with over 32. And then we all know about MELD in Great Britain. The Glasgow score is widely used. And the LIL score is a different score in that it's a dynamic score waiting for the reaction to day seven, but you could also do this at day four. It's to identify when you can stop corticosteroids. And if any of you heard Philippe Maturin talking yesterday, he also referred to a LIL paper which combines the LIL score with the MEL score. So here's what the guidance says. Lab-based prognostic scores should be used to determine prognosis in alcoholic hepatitis. And we have gone for the tried and true and said the Madre discriminant function greater than or equal to 32 should be used to assess the need for treatment of corticosteroids or other medical therapies. And a MEL score greater than 20 should prompt consideration for steroid treatment. As you can see, this is a guidance. We're not telling you you have to treat with steroids because we know the weakness of the data. And then abstinence from alcohol should be promoted to improve long-term prognosis. So here is a rather fussy algorithm that gives you some idea of what you might do. You have a patient who was presented with suspected alcohol-related hepatitis. You rule out infections and other complications. You apply here the NIAAA definitions. If it's definite and you have a biopsy, or if it's probable, you don't need to consider a biopsy. If it's confusing, you should at least consider a biopsy. And then you calculate the Madre discriminant function. If it's high and the diagnosis is in doubt, that's what they put it in this point, the biopsy there remains. And then you can start with prednisolone and you can assess the LIL score at day seven. But you could use a shorter duration. Ramon Batiere and his group have published that four days works in a single center. So wanting to avoid the unwanted effects of prednisone is reasonable. And if the patient is below 32, you continue the treatment, but this is a population who's at increased risk of 180-day mortality. Some of that risk is from return to alcohol use. So intervening in these patients with treatment for alcohol use disorder is really a crucial intervention. And then you have the LIL score and there are some people who are responding. You continue for 28 days, but we are challenged by the people who are not responding. And there you can either consider liver transplantation or a participation in a randomized controlled trial. And there are many products coming available and hopefully we may have a trial also of liver transplantation. And so I would strongly urge you to see if you can accommodate the recruitment needs of these trials. We need them very badly. So just moving on with our, is that, let's see, have I gone the wrong, no, tried it. I'm moving on here to liver transplantation. And this is to show you some recent data I've taken from Eunice, which shows that black is alcohol-related liver disease and you can see the registrations on the transplant list for ALD are rising. This goes up to 2016. The registrations for hepatitis C are dropping and they've dropped even further. And NASH is chasing neck and neck with alcohol. And similarly, the number of transplants is going up. So alcoholic liver disease, as this is caused in the title of this paper, we would now say alcohol-associated liver disease or related liver disease, replaced hepatitis C as the leading indication in the years observed. And that growth probably is going to continue. There may be a plateau for it. We're not sure. But the real area of concern here are those patients whose alcohol use disorder is what makes them difficult candidates. And the most obvious group in that setting are the patients who have been drinking recently. And they are the patients with alcoholic hepatitis or acute and chronic decompensation with alcohol. And so what about those patients? Well, the recent data in the United States is retrospective data coming from the Accelerate group, a multi-center group who gathered retrospective data across America under the auspices of Brian Lee and Nora Turow. And here you can see the patient survival. There were just about 150 patients in 12 Accelerate sites here. And the survival out to three years for the patients with alcohol-related cirrhosis compared to the patients transplanted for alcoholic hepatitis seems the same. So this is different from the earlier data of Philippe Maturin. And one of the reasons probably is that his patients all had seven days of corticosteroids. Not all of the patients in this group did. And the problem for those patients is infection. And so he had a higher rate of infection, particularly fungal infection. He has now done a randomized comparative trial, completed the recruitment, and they're waiting. They either are about to finish or have finished the follow-up period. And so we hope that's going to be available for review very soon. And what about drinking in this group? Now, a more nuanced version of these data were presented yesterday at this meeting by Gene Im, one of the co-authors of the guidance. But you can see that according to the methods of record at each of the centers, 33% of the patients recorded some drinking post-transplant. And when we distinguish slips from sustained use, 17% did. So you can see we recognize that alcohol use occurs in these patients. And we also saw in this data set that those persons who returned to drinking early had an increased rate of alcohol-related deaths. It's also remarkable that the percentage who did not appear to return to drinking was so high. And that's worthy of further investigation as to why that is. There is no other circumstances in treating alcohol use disorder in which the sustained abstinence rate comes anywhere close to this. So what does the guidance say? Patients with decompensated alcohol-associated cirrhosis, child's class C or a male of greater than 21 should be referred and considered for transplantation. So we make an active suggestion of encouraging referral to transplant centers. Candidate selection should not be solely based on the fixed interval of abstinence. So this is a complete change from the previous guideline, which endorsed six months abstinence as an absolute requirement. And finally, it says liver transplantation may be considered in carefully selected patients with favorable psychosocial profiles in severe alcoholic hepatitis not responding to medical management. Now of all the parts in the guidance that caused further discussion and negotiation, this sentence was the one that caused the greatest concern for fear that this is going to release into the transplant programs a host of patients who shouldn't be transplanted or else that is going to be too restrictive and prevent patients. So this doesn't say, it doesn't say everyone needs to be considered, but they may be considered. And they are carefully selected. And you know that they've got favorable psychological profiles and they have failed treatment. There are a lot of qualifications there, but it still means that this guidance has endorsed the notion that some patients with alcoholic hepatitis who haven't been drinking recently are appropriate candidates for liver transplantation. So I'm just going to leave you now with my take home points from this exercise in guidance development. It's been a privilege to be part of the group writing it, but I want to emphasize how involved the Guidelines Committee, George is not just the best emcee for a meeting here, he's the best director of a committee as well. So they were very involved as really cooperative writers of this and with the board. So the patients with ALD have two diseases. That emphasis is new in this guidance. Secondly, we are trying to adopt a less stigmatizing nomenclature and terminology regarding alcohol use. And we are promoting SBIRT, screening brief intervention, referral for treatment, and we offer Audit C as the screening tool. And all interventions start with advocating for alcohol cessation. So we do appear to be trying to say two contradictory things at the same time. You know, where if we want alcohol cessation, we know we might not get alcohol cessation. But I have an advantage over many of you because I am Irish and I am a balanced Irishman. And the definition of a balanced Irishman is an Irishman who can hold two contradictory opinions at the same time. And so this is, you have to be able to live with that nuance here. We are still in favor of alcohol cessation, but we recognize that that's a counsel of the ideal. We also recognize the weakness around the effectiveness of corticosteroids, but we still think they have some benefit in some patients. And we encourage those of you treating these patients to look for that. And this is in particularly the patients with severe alcoholic hepatitis. And there are many new treatments coming, but constructing meaningful randomized controlled clinical trials has proven difficult. And the greatest difficulty has been recruitment. And recruitment relies on you. So really try to encourage recruitment in your centers. And finally, liver transplantation is established for life-limiting alcohol-related liver disease, including some patients with short intervals of sobriety. And I'll stop there and thank you for your attention. Thank you. So I want to invite Dr. Julie Heimbach and Dr. Keith Linder to come to the stage. And while they're coming up here and you're preparing your questions, please come to the microphones and introduce yourselves. And I wanted to introduce also Dr. Amit Singhal, who is the co-moderator and vice chair of the Practice Guidelines Committee. And he was presenting his own original research and so couldn't make it from the beginning. So if you have questions, please come up to the microphones. Microphone 8. Okay. Thank you very much. Robert Mitchell Thane, PBC Foundation, UK. Thank you very much and congratulations on your work. Given that there's a president already set with other academic bodies, my question is how do you feel that we can move forward in accessing all of the expertise available within the community, and particularly incorporating the patient voice and the experts of those living with conditions? Thank you for a very easy question to start out with. It is a challenge, and I think we've increasingly tried to both recognize and incorporate the patient voice. I think the Guidelines Committees haven't done that yet. It's probably time to think about doing that. I think that when patients get involved, the questions that they ask, the answers that we try and provide, are shaped differently in an important way. And so I think that, at least speaking for our work and doing the one for PBC, I believe we would have been helped by having more patient involvement. So I think we appreciate your group's interest in this and pushing us more and more to do this. I think it's an important point you raise. Maybe I should say, from the Practice Guidelines Committee standpoint, that, yes, we are considering having an open comment period specifically so patient societies could comment before the guidelines become published. Microphone 4. This is Ashutosh Barve from University of Louisville. And I don't mean to cause a fight on the panel or anything like that, but I was just very curious to see what the HCC Guidelines Committee would think about the PBC Guidelines Committee's recommendation regarding surveillance for HCC and PBC with men. I'm referring to the fact that Dr. Linder talked about maybe doing surveillance in PBC with men who don't have cirrhosis or stage 4. So this is the first time, really, we've recommended HCC surveillance. As I said earlier, oftentimes there was, I think, a misnomer that patients with PBC were at very little risk. So I think that this was a step forward to do that. When we've looked, it was really males had the increased risk, as did patients with more advanced disease. So we tried to be careful. At one point, there had been a paper that suggested anybody with PBC was at a higher risk, and surveillance for everyone was recommended. But the data really didn't support that, and so we were trying to be cautious and recommend surveillance for those groups of patients that seemed to be at the highest risk. Just simply that. And so in the HCC guideline, we could talk about the cases where there's clear evidence that this should be done, and that's certainly in patients with cirrhosis from PBC or any other cause. And then there is a fairly nuanced discussion of all of the other categories where we cannot be as certain with the recommendation, and there is a short discussion of PBC, but I don't think we came down to it to really push it in any direction. I don't know if you have anything to add to that. Yeah, I think Keith's point of, like, raising awareness of this is an important issue. And then now, you know, it's going to be on us to, you know, really evaluate this and get better data in terms of the incidence, the cost-effectiveness. But I think in part, you know, the guidance is also trying to, like, undo some of the misconceptions that have existed in the past. I think microphone 5 is next. Thank you. Juan Gallegos from University of Utah. To Dr. Lucey and his colleagues, I think the guidance document is very relevant to our practices. How do you think this will help us get our patients linked to mental health or addiction treatment? Because a lot of these patients are underinsured or uninsured, and even in insured cases, mental health or addiction medicine is hard to get into for these patients. Thank you for that comment, because it's very relevant to the way clinical practice is established in the United States at the moment. There aren't enough mental health professionals available for patients, and there are many barriers between connecting patients with appropriate mental health expertise. So that was one of the reasons why I suggested that we need to increase the mental health literacy among our trainees. Of course, it starts with ourselves. We are products of the same training paradigm in many ways, but this is a time for change. So I hope that this guidance is a call to arms in the field of hepatology, transplant surgery, gastroenterology in general, and not just among doctors, but also among nurse practitioners and physician's assistants, all of the people who see our patients, and then perhaps we will see a ripple effect back out into the community. I think we have microphone 10 up on the balcony. Sorry, I didn't see you earlier. That's okay. No, thank you. Yeah, this is a fantastic session, and I'm hopeful this continues every year at ASLD. My question is about the alcohol-related liver disease, particularly severe alcoholic hepatitis. Did the committee think there was enough literature to comment on nutrition in that population with specific goals for calories and protein intake for recovery? Well, thank you for the question, and I probably should say that I have not listed every guidance statement that is in the guidance. So there is a specific area referring to nutrition. Many of these patients are malnourished, and just as we need assistance with mental health professionals in maximizing the care of the mental health of these patients, we also benefit from the assistance of experts in nutrition, and so this is not absent from the guidance, and your point is very well taken. My question is regarding biopsy in indeterminate cases of HCC. There's a lot of concern about tumor spread along the biopsy track. How often do you see that? Yeah, so the question is about the role of biopsy in an indeterminate nodule, and one of the downsides of that being that seeding along the biopsy track. So there are different ways to perform the biopsy, and if you can utilize a technique where you use, you know, ablation on your way back from the biopsy, that's one strategy, but I think the published risk is around 2%. And then also over time, you know, with the coaxial needle technique, the risk of tumor seeding has actually been, has dropped since the original studies, and so I think that if you use a coaxial technique, the risk of tumor seeding is not zero, though I think the updated data with using that technique is actually much lower. Than that published 2%. Yeah, yeah, so I think the 2% is like really taking all comers, and so the new proportion with tumor seeding, I think, is less than 1% using a good technique. I think what Julie's point of actually using this with ablation and burning the track is another way to reduce the risk of seeding. I think the one thing about this is just also to make sure that you're doing biopsies in patients for indeterminate nodules that will actually change clinical practice. I think one of the key things that changed in terms of the new guideline was actually saying you could repeat imaging versus biopsy, and so at least in our center, we use biopsy only if it's going to acutely change management, and otherwise they're comfortable doing repeat surveillance. Microphone one. Thank you for the nice lectures. I want to refer to the alcoholic lecture, and the definition are very important, and maybe you should add also AU, which is alcohol use, because mostly people that drink alcohol, they don't become alcoholic or alcohol liver disease patient, and I think that education can be also very important because some of the sick people that have alcoholic liver disease, the alcohol-induced liver disease, they didn't drink too much, but in fact nobody explained them that the amount that they drank was too big. They had maybe a bit of elevated liver enzymes. I know a friend that stopped drinking because he had a GGT elevated level, so we should also educate our patients so some of them we can prevent. In some of them, we can prevent alcoholic liver disease. As Chekhov said, it's a problem that it's difficult to treat. Well, in fact, Chekhov himself used to drink with some of his patients, especially the dying ones. Well, thank you for that question. There are many nuances in what you say, so just on definition, the definition of what is an alcohol use disorder has gone from a U.S. perspective, a series of changes consistent with the DSM programs, and we are now using DSM-5, the Diagnostic and Statistics Manual 5, which is this experts' codification of psychiatric diagnoses, and in that they abandoned the distinction between alcohol abuse and alcohol addiction. They now see it as mild, moderate, and severe, and the mild were the old alcohol abuse group, and that was a useful distinction for the very reason that you make, because those patients had a far better chance of stopping when told this is deleterious to your health, and so that observation still is true. It also goes back to what I said earlier about recognizing that there is a problem, and so that falls back to us to ask the right question and be aware so that we find your friend who only has an elevated GGT. It is right that that patient stops drinking. He will prevent himself from progressing further by doing that, and so everything you said is very, very relevant. Thank you very much. Microphone 7. Yeah, thank you. Dr. Mandod from India. My question is for Dr. Lucy. About the newer treatments in alcoholic hepatitis, I just wanted your opinion which seems to be the most promising for the near future, because a lot of patients cannot be given steroids, so what would be the options in the near future for them? So they're all promising at the start, unfortunately, and that's why we need better studies. So coming from India, GCSF has been very, very promising, but we need well-constructed, well-powered studies to look to the outcome there. So it really is a question just to allow me to say how important studies are, both treatment for alcohol use disorder within the context of alcohol-related liver disease and treatment of alcohol-related liver disease. We had a fantastic lecture at the alcohol SIG meeting, the symposium yesterday from Vijay Shah from the Mayo Clinic. So the future is very bright, but it's a little bit like one of those stands you sometimes see at local carnivals where you throw a ball and knock down a duck or something and you get a prize. These new treatments are all like the ducks, and many of them are knocked down once they're put towards a proper trial. So rather than say which one is more promising or less promising, I would say support the trials that you can have access to, and then we will get the data as to which ones really work. Thank you. Microphone 6. I recently was in Alaska, and I went to purchase an alcoholic drink, and in Alaska now you have to have a driver's license which indicates whether you've had trouble with alcohol in the past. And that recently passed law led me to question whether we should consider driver's license restrictions as part of our considerations for patients with alcohol use disorder and the need for liver transplantation in an effort to try to reduce the availability of the substrate to those individuals. I'm not sure who you're addressing, but I'll take the question seeing that I'm the alcohol person, not the alcoholic person. I think I've made that point clear. I'm the alcohol person. The broader area that you're addressing are social environmental efforts to reduce drinking, and the drinking that's attempting to be reduced is harmful drinking. And social interventions of these kinds can have a beneficial effect. I can't speak directly to the Alaskan model, but the one that is most recent that I'm familiar with has been the introduction in Scotland and then in Ireland of an elevation to the minimal pricing unit for alcohol. If you make alcohol more expensive, people who are spending all their discretionary cash on alcohol will actually drink less, and you will reduce the injury both to them and to society. So the United States has a more troubled history with regard to social intervention regarding alcohol, and so there's always the question, are you trying to reintroduce prohibition? I'm not suggesting that, but I am suggesting that there are social interventions that can make a significant improvement to health here. Microphone 1. Elina Krutishpin from Lisbon. My comment is also an alcohol-related liver disease. In fact, I want to congratulate ASLD for changing the nomenclature. We also have done that in its last guidelines, and I think that's a very important point. The other point I wanted to comment on is regarding liver transplantation in alcohol-related liver disease. In fact, I think that the main reasons why in certain occasions you don't transplant a patient should be related either to very bad social surrounding or to the fact that there is the capacity to recover, and so sometimes the abstinence period is more beneficial for giving this possibility of recovering. Because otherwise, I think there's no reason to not transplant a patient because we transplant patients with many self-inflicted diseases, so I think that should never be a value, a judgment of value. And finally, my last comment is also regarding the policies, but you already mentioned that, in fact, there are policies that are very effective in preventing alcohol use, such as those that are related with taxation and with decreasing the affordability of alcohol, such as the minimum unit pricing. So it was Mark. Thank you for that. Your comment about the potential for patients with alcohol use disorder and liver disease to recover with abstinence is known to all of the people here who actually see patients like this. Everybody has had that experience, and that is the reason why we really would like prognostic instruments that were more accurate than we have. The limitation is the limitation of the instruments, but the goal of separating out the patients who recover and not transplanting them and addressing their alcohol use disorder is a very worthy one. Microphone 7. Vince Bain from Edmonton. Thank you to all the speakers and the committees for all the great work. My question is to Michael Lucey, and it's about the discriminative function. It requires you to look at the PT in seconds, and different reagents are used in different labs. That's the whole reason we have the PT-INR. Yes. So given blood sample done in Edmonton, done in Michigan, done in Texas, might yield a different discriminative function. Sure. So we've gone away from that, and I was just a bit surprised that it was so up and center in the 2019 guidelines. I think your point is very well made, Vince. The reason is because when you're looking at the written data, it has the most data. That's just its age. But your point about that you have to get the PT in seconds and know the control is a complicating one. And then the variability of PT, that's also absolutely correct. And it also speaks to this issue of the persons with a discriminative function below 32 but still having a serious illness. And so, yes, I accept those weaknesses. We've offered an alternative in MELD, but, yes, your comments are well taken. Thank you. So hopefully time for two short questions. So microphone 6, and then we'll go to 10. Hi, Dr. Lucey. I'm going to quote Chekhov to you again. Of course. I quote, anyone can face a crisis. It's day-to-day living that wears you out. And the day-to-day living that wears you out that I'm talking about is the duration of the primary care visits, which is at best 7 to 10 minutes. And given the slides that you showed us and the burden of alcoholic-associated liver disease and the socioeconomic effects that it has on the best years are the prime of their life, do you think ASLD should have a call to action to whoever mandates the 7 to 10 minute primary care visits to increase that and to somehow incorporate the alcohol questions into the clinical visit? Well, there was always a danger I was going to be out-Chekhov'd once I mentioned him. It's a common problem now because of the ease of access to the internet. I only know one other Chekhov quotation, which he said, marriage gave me my wife and literature gave me my mistress. And so we are fortunate that he spent as much time with his mistress as he did because of the wonderful work that he has left us. To go back to your point, though, you're asking really a policy question and a functional policy question, which is outside my area of expertise, really. I'm not quite sure how best to invigorate the primary care community to do this. I suppose rather taking a line from the earliest speaker here today who pointed out the importance of having patients at our negotiations, the same would be true before the ASLD embarked on this. We need to hear what the primary care societies tell us about what they're doing and what the barriers they face to doing this and learn their day-to-day living in a way that would enable both of us to improve what we're trying to do. I'm sure they would agree on the value of early intervention and recognition of alcohol use disorder. It's how to make it work, and we really need to hear how they feel about that. But I take your point. So one last short question from microphone 10. Okay. Thanks all, Professor, for a nice lecture. I'm Dr. Chota Tun from Myanmar. I want to present with one case. I have a 40-year-old gentleman who is a chronic drinker presented to me with severe alcoholic hepatitis. He has gone more than 32 in previous four months. I treated him, but apart from that, he also has underlying alcoholic cirrhosis and child B, and I treated him with corticosteroids. But still now he improved, but still now he had bilirubin above around about 11 mg per deciliter. Apart from that, other lab parameters are in normal range. What should I do? Should I consider or persuade him for liver transplant? He is doing well. Apart from that, he is doing well. One of the things that came out in the literature in the last 12 to 15 months were two papers, one from Alta Merano and one from Alex Louvet and the group at Lille. The Spanish paper is a retrospective paper. The French paper is prospective. Looking at the outcome of patients who survive an episode of severe alcoholic hepatitis. Both papers have the same conclusion. The significant factor that leads to mortality after a successful recovery from an episode of severe alcoholic hepatitis is return to alcohol use. So the first, I would hesitate to give advice about Myanmar. You've got to look at what happens in your own society, and there will be local factors there that are outside my knowledge. But if we take this as a global phenomenon, then the first thing to question is the patient really abstaining. How would you find that out? Well, you start by asking the questions. Another thing you might choose then would be a biomarker. The biomarker that we are using most now is phosphatidyl ethanol. It's done in whole blood. It's simple to use. It's important that the patient knows you're doing it because this should not be a sort of gotcha type of test because that then produces a very awkward breach to the doctor-patient relationship. You're saying to the patient, I found out that you're drinking, and he says, I'm not, and now you've got a loss of trust. But if you say, I'm going to do this test that has a high sensitivity for alcohol use and reflects alcohol use in the last two to four weeks, and you could say, have you been drinking? Have you been drinking? If they say no and then you get the positive answer, then you say, we really need to have another conversation about this. This is what this looks like. And so I would start with that. I would start with the question of whether this patient is really abstaining. Yes, for that, Professor, I'm sure that he is abstaining because during treatment he also had an episode of GI hemorrhage, and he is very afraid of that, and he is sure for abstaining. I still would stay with what I said. It may be that he's abstaining, and then you may need to think about liver transplantation, as you suggest. But I would look to see the capacity of the human mind to forget something as awful as a variceal hemorrhage is extraordinary. Thank you, Professor. So this was a great session. On behalf of myself, George, and the rest of the Practice Guidelines Committee, I want to thank our panel, Keith, Julie, Mike. I mean, really great to have you here. Really quite a great discussion, a lot of good answers to several of the questions that come from the guidance and the guideline statements that's come out over the past year. Once again, thank you.

alcohol-associated liver disease

guidance

alcohol use disorder

culture change

stigma reduction

screening

brief interventions

referral for treatment

severe alcoholic hepatitis