So I'd like to welcome everyone and thank you for joining us. I am Ryan Lee and I'm a transplant hepatologist from University of Southern California and I'm very enthusiastic to be co moderating this ASLD webinar optimizing the liver clinics role and managing alcohol use disorder among patients with liver disease. So this webinar that we've been planning for several months now within the ASLD, ALD SIG, we're aiming to provide a very clinical, applicably, overview of steps that our providers in a liver clinic can take to address alcohol use disorder for their patients with liver disease. You'll hear from multidisciplinary perspectives but the focus is really on what is realistic and practical for an everyday liver clinic, which can have variable resources and patient populations. So we'll have three speakers, followed by an interactive question and answer period at the end of the webinar, and you can send your questions throughout the session in the Q&A button at the bottom. And I'll now turn it over to my co moderator Dr. Leanne Gunskell to introduce our speakers. Thank you so much again for joining our webinar today and again my name is Dr. Leanne Gunskell from Indiana University and happy to moderate this session with Dr. Brian Lee. Our first speaker is Ms. Liz Lee. Ms. Liz Lee will be talking to us about the disparities and stigma and access to the treatment for patients with alcohol use disorder and liver transplant. Ms. Liz is a nurse practitioner at the Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network in Canada. She is a previous award recipient of the ASLD, NP, and Physician Assistant Clinical Hepatology Fellowship, which helped launch her career as a hepatology nurse practitioner. Ms. Liz's main focus is on the management of patients with cirrhosis and alcohol associated liver disease. She's a current ASLD 6 steering committee member for ALD, a founding member of the Canadian Association for the Study of Liver Disease on ALD. Liz, looking forward to your talk. Thank you so much for that kind introduction. And I'm going to share my screen now before we get started. And thank you also to ASLD for giving us this opportunity for putting together this session today. And I'm just going to put myself into presentation mode. All right, so thank you very much for the introduction and for setting the stage here. I guess I get an opportunity to set the stage for my two esteemed panelists that will be presenting and providing really tangible things that you can be bringing into your clinical practice, even as early as this afternoon in your clinic. And so I've been tasked to speak about the disparities, stigma, and access to alcohol use disorder treatments with patients with liver disease. And these are my disclosures, and there's nothing relevant to today's presentation. And as Sukha has already mentioned, so my clinical practice is really around a lot of readmission avoidance. I see a lot of patients with decompensated liver disease after they've been recently discharged from the hospital. And there was a lot of pressure in terms of being able to prevent readmission. And at the main etiology, and over 50% is with people with alcohol associated liver disease. I do have a separate practice where you do see individuals at ALD across the chronic disease spectrum. And I think that is a good complementary practice. And when we think about opportunities to intervene in early alcohol associated liver disease, as well as with alcohol use disorder, and with the prevention of liver related complications. But I think that all of those of us that are attending here can appreciate that it is a pretty challenging, it is a complex patient population. I think that there is a lot of aspirational things that we like to do in our clinical practice. I think over the last couple of years in which I have been a part of this role now, there have been some evolutions and changes that have helped with improving the practice. And I think a lot of it is related to some of the things that we could potentially do a little bit further upstream in order to provide equitable access to all patients with alcohol associated liver disease. And so my main objectives here, I will have a brief overview of epidemiology and trends and alcohol use disorder and alcohol associated liver disease to set the stage. And I'm going to limit it really to discussions of US and Canadian data, but recognizing that there could be similar challenges globally also as well. And then afterwards, I will then talk about the access to alcohol use disorder and alcohol associated liver disease care, really mainly talking about health disparities. And then I will end with a little bit of a reflection, a reflective piece that will help with setting the stage for some of the ongoing conversations around the care for alcohol use disorder and alcohol associated liver disease. All right. So first, I'm sure that we've all had an opportunity to really define what a standard drink is. But it's important that we are starting from the same definitions. Our definition as a standard drink may be definitely different than what our patients are defining as a standard drink. But again, you know, a drink means that beer, it would be a can of beer, or a bottle of beer, not a tall boy. So, and it would be about 5% ADV, similar with ciders. Wine would be a five ounce glass, not a nine ounce glass and distilled alcohol or spirits would be 1.5 ounces of alcohol. In terms of defining what is excessive drinking. So in the US, that is defined as more than four, 14 standard drinks per week. And for women, it's more than seven standard drinks per week. In Canada, the Canadian Center for Substance Use and Addiction had recently revised their guidance document and that actually had just come out in early January this year with a lot of uproar actually. And so, and but that is now excessive drinking is now being defined as more than six standard drinks per week with no gender differences. And so I'm going to shift and talk a little bit about the epidemiology of alcohol use disorder. And so in Canada, and as well as in the US, I think what we can appreciate from the data is that it is very likely that amongst the people that you see in your clinic today, or beyond in the general population, that there is probably going to be a certain percentage that that exceed low risk drinking guidelines. And so for us, and what we see in our clinic over like the last, last decade, is that it definitely has led to a rise in hospitalizations. And in fact, in some areas, it's also outpaced the rates of hospitalizations versus heart attacks. It is definitely the largest increase in rates of visits and age standardized rates in these visits amongst young people and particularly women. In terms of the epidemiology of alcohol, social liver disease in both countries, we do see that there are similar trends in terms of the increase in annual incidence of alcoholic hepatitis, an increase in hospitalized cases of alcoholic hepatitis with a high degree of mortality related to complications arising from portal hypertension. And again, I think what has been appreciated over this last decade is that there is a high significant rate of individuals that are young, with like the highest average annual percentage change in mortality driven by alcohol associated cirrhosis. And I think that over the pandemic, it's hard to not talk about the pandemic in the sense where it has had a lot of implications and effects on the healthcare system and the pressures to the system. And definitely over the pandemic, especially during times of high stress and high impact with a lot of individuals also precariously employed and with loss of employment, it has also exacerbated a lot of alcohol use as well. So what we have seen as similar trends in both countries is the rise in alcoholic beverage sales, significant increase in average monthly alcohol hepatitis admissions, a surge in alcohol use disorder and alcohol associated liver disease related mortality, and as well as young patients showing the largest increase in AUD mortality compared to other age groups. And so I think when we look at this data as a whole and bringing it back to what this means for liver providers, first of all, I think one is appreciating that it is a younger patient population. I think that we are also seeing that this is what is stressing our clinics and the demand for liver providers. And I think for us as liver providers, we all know that the cornerstone for improvement of alcohol associated liver disease outcomes is alcohol absence. And we also know that a central component of the management of patients with alcohol associated liver disease will be related to the ability to effectively screen and treat alcohol use disorder. And while this sounds fairly simple, it's definitely easier said than done. And I think this brings us then to thinking a little bit more, and this is more of the reflective piece of it. And so as liver providers, we have a very large toolbox. We have a lot of tools that we readily pull out on a regular basis. But we seem to pause when we think about treating people with alcohol use disorder. And so there's a lot of questions that is more of like a knowledge piece, a time piece, access piece. And that's actually part of what's driving today's conversation. I hope that our speakers a little bit later today, they will be providing you with some of these tools and around knowledge. So that way you're able to bring into your practices. It's hard to talk about the toolbox and why we may hesitate pulling this into our toolbox as well, without also thinking about some of the social disparities. Some of the access to substance use resources, and ultimately the big arching theme around stigma, either from a societal level, a provider level, from self also as well. And so when we think about social disparities and access to care, and this is a really great graphic that was actually part of like a recent article that was published in the clinical liver disease. It was touching upon social disparities and access to alcohol use disorder and alcohol associated liver disease care. I think that we can all appreciate, especially with a younger cohort, but in general, that a lot of the individuals that are not joined by clinic, or the ones that have difficulties in engaging in care, that is not just because they don't want to engage. It could be also because of a lot of other competing priorities and different factors that could be limiting in terms of their ability to engage in care. And I think on this particular slide, it really does highlight the need for a holistic approach that also addresses the psychosocial barriers to accessing care. And that is perhaps beyond what our liver providers could do, but it also then invites the conversations and collaborations with other providers, with multidisciplinary providers, such as social work, such as psychiatry, such as addictions resources, both within hospital, but also in community. Then by being able to develop this network, it could also perhaps better be able to support these individuals that do want to engage in their care and their liver health. And I think it's important to think about these things and even further upstream before they do present to the hospital, because we all know as liver providers that by the time they present to the hospital with symptoms, they are presenting very late in the disease process. And these particular social disparities in terms of accessing liver care are the same issues that are going to arise when we're thinking about access to treatments such as liver transplant. So this is the one piece and where I will talk about something a little bit more local. You may have also heard about a lot of this also in your own work also as well. Our liver transplant program here was involved in a pilot project with our province, so I live in Ontario, and where they had looked at revising the six month absence rule. And by doing that, part of the pilot was about whether or not it could be changed in terms of how people were being evaluated. So just for some context, the way people are being evaluated is separated into two separate phases. One is a phase where they assess individuals from a psychosocial perspective. So whether they have social support, so a social work assessment, but they then also then look into their risk for relapse, and that's done by a transplant psychiatrist. And if someone is able to proceed to medical evaluation or pass those assessments, then they proceed to medical evaluation. And that's actually how this table is constructed. So on the left, you see that it's the psychosocial profiles and the individuals. In the middle are the individuals that actually proceed to medical evaluation. On the right is then those that were declined. And what you can see that was statistically significant are those that were accepted patients. Typically were individuals that were older, individuals that did have a lot of social supports, and those that were actively employed also as well. And one of the striking things, and especially for our Ontario group, you know, and because I do live in a province where it is fairly culturally diverse, it was actually really surprising that while it wasn't statistically significant, it was surprising that most of the evaluated patients were white. And so it did raise some questions about whether or not there were some structural inequities in terms of being able to access care. And I know that some, our group has collaborated with some other providers also as well in order to do a deeper dive in order to understand this phenomenon also as well. And this is another graphic taken from the same paper from Dr. Plumbing's paper from clinical liver disease. And I think this is a really great way to really think about the individuals and what we hope to be able to achieve. And so I think today we're going to talk a little bit more from a provider level, and this is what we hope to do. Some of these other pieces around what we hope to be able to aspire to do from like a hospital level, also in terms of being able to address the disparities to accessing care, also in the research inclusion of populations that reflect the general populations. And finally, I think from a societal level is then how do we reduce stigma in individuals with alcohol use disorder and alcohol associated liver disease? And I think this is like a really big, important piece, because I think that without addressing this as like an overarching piece from a cultural perspective, it is actually really much more difficult to be able to deliver care overall. And so for the last few minutes, I will speak a little bit about this. And so I did actually look into the definition of stigma because I did want to think about that a little bit more and be able to define it properly. And so it does have some Latin roots. It also has some Greek roots also as well, but essentially to meaning mark, brand or to tattoo. And it was first used in English actually to refer to a scar that was left by a hot iron, so a brand. But in the modern use and the way we use stigma these days, it's really more figurative. It really refers to the social cognitive process that starts out labeling someone, thereby creating an out group described by this label. And so it oftentimes it does evoke prejudice. It evokes negative emotions, reactions towards the labeled person. And so we often then get things like we get people calling individuals with that use alcohol as alcoholics. There is a lot of culture that's related to this around individuals being undeserving, calling it something that is self-inflicted. And even amongst like the providers, there is something called disease prestige where people like providers may select to not care for particular individuals because they might be associated typically with more social disparities also as well. So there's a little bit of that as well that's associated with that stigma. And so when we think about stigma, I think that from an individual, someone living with alcohol use disorder and alcohol-associated liver disease, there are things that they are trying to navigate around. And depending on the type of stigma, so public stigma, self-stigma, and structural stigma, that could really inform how an individual then might react and how they might behave. And that could then, but ultimately I think at the end of it, that impacts the individual's ability to be able to engage in care. And oftentimes people do delay actually seeking medical attention. It often then leads to suboptimal care. And for a lot of us that can appreciate in this virtual room, it does lead to negative health outcomes. And so when we think about addressing stigma as a liver provider, I think it's really also important to think about in terms of self, what we do as an individual provider to help with fostering some of this cultural change. And I think some of the important pieces is really shifting away from that dichotomous distinction between those who are addicted versus those who are not. So being able to shift away from a language of personal responsibility. And I think that as liver providers, we do also have a responsibility to educate the public also too, in terms of like normalizing discussion around care priorities, as well as the continuum model of alcohol use disorder and alcohol associated liver disease. And then from a structural level is in thinking about how we could optimize care in our clinics that would require perhaps a structural change in terms of from like an organizational level around how we do actually enhance prevention in early detection, both in primary care and specialty care, how we think about integrating care around addictions, how we enhance the care with the use of a multidisciplinary team, particularly to underserved areas, as well as continuing evaluation of liver transplant policies as well. And this is some of the last thoughts I will leave you with. And this is, this graphic is taken from a paper that was written by Annie Kardashian, Marina Serper, Nora Toro, as well as Lauren Matthew, and who have spoken. And I think it was a really nice paper, also talking about the cultural disparities, the health disparities that exist in liver disease. And this is really, I think what we, and I think it's really reflective of what we see. And I just had want to leave us with this. Because I think what we are seeing right now in our clinical practices a lot of time is that really a downstream effect of what has been happening further upstream. And that's what we've currently seen. What we aspire to be able to do is being able to address things further upstream to prevent downstream consequences. And this is where we could potentially be able to develop quality improvements and implementation of strategies to improve current clinical practices. And much further upstream is really about how do we change things. And I think this is probably the most powerful piece around stigma, is then how these cultural values and changes could potentially then improve what we do down the road also as well. And so my takeaway messages for today is really a few things. So what we do see is that there is a rise in alcohol use disorder and alcohol-associated liver disease, particularly in younger patients. So thinking about care and how it could be tailored to age-specific considerations. Knowing that patients with social disparities are disproportionately affected in their access to alcohol use disorder and alcohol-associated liver disease care. And finally, I hope that this is definitely not going to be a today, but you can take away for tangible practices now. But I hope that you do think about these things in terms of how you care for individuals and continue to advocate for change is really around how we then continue to address stigma around alcohol-associated liver disease and alcohol use disorder. And that's all I have for now. And I will pass it on to the rest of my esteemed panelists. And I hope to engage with all of you in the discussion after. Thank you. Thank you so much, Liz. That's a great talk as an introduction to our next speaker. Our next speaker is Dr. Michael Lucey. Dr. Lucey will be talking to us about screening for alcohol use disorder, monitoring alcohol use and alcohol counseling techniques that a clinician can apply in the liver clinic. And you all know Dr. Lucy very well. He's a hepatologist and chief of the division of GI hepatology within the department of medicine at University of Wisconsin in Madison. Dr. Lucy is a medical director of the University of Wisconsin liver transplant program. And he has been elected as an ASLD counselor and will serve as our president in 2027. Mike, looking forward to your talk. Well, thank you very much, Suthath. And thank you to you and to Brian for the opportunity to talk here. And I'm going to follow on what is a really a lovely introductory talk. And you'll see that what I've got to say complements what you just heard very, very well. So I'm going to address two things about optimizing the liver clinic's role in managing alcohol use disorder among patients with alcohol-associated liver disease. Really, first of all, the why we should do this and then to try to address a little bit of the how. And regarding the why, the first is a statement that has already been made that all treatment of alcohol-associated liver disease begins with abstaining from drinking. So that's our goal to try to enable our patients establish sustained sobriety. And it's in the setting of alcohol-associated liver disease. And what is shown here, which is a graphic from the ASLD Guidance on Alcohol-Associated Liver Disease, David Crabb is the first author. The material in this slide, I'm sure, is familiar to many people listening to the webinar. The red arrows are signs of deterioration, chronic and excessive alcohol consumption. And the green arrows are abstinence from alcohol and what might happen. And so patients start with a normal liver. And if they drink enough, they will get fat deposition in their liver. That's just a natural phenomenon. And if they then established sustained abstinence, many of them will lose that fat. So that's a dynamic that we know. And then some of those patients with fat in their liver may then develop an inflammatory process in their liver, which at a histological level is called steatohepatitis. At a clinical level is alcohol-associated hepatitis. And that too is reversible in some patients if they stop drinking. And some of the patients with steatohepatitis progressed to cirrhosis and some of those unfortunately to hepatocellular carcinoma. But we're now recently concentrating more on a further aspect of dynamism in this. And that is the return to a compensated state from patients who had decompensated alcohol-associated liver disease. And again, abstinence is the key to that process of regaining compensated liver function. And so that is the reason why we want to encourage patients to stop drinking because of the potential for them to improve their liver health. And the data are now emerging that addressing the alcohol use disorder may have a beneficial effect on the alcohol-associated liver disease. And this is a recent paper from the group at Harvard published in JAMA. I recommend that you see it. Augustin Vanier is the first author, but it was an observational study, not a prospective treatment study, but an observational study in which some of the patients with alcohol-associated liver disease were also given treatment for alcohol use disorder. And then they just looked at a Kaplan-Meier analysis of the association between treatment and decompensation. And the treated group had a far lower rate of decompensation than the untreated group. So treatment enables patients to avoid decompensation. So that gets me to what are the things that are retarding us from reaching these goals? What are the pitfalls in management of alcohol use disorder in patients with alcohol-associated liver disease? And the first is a lack of early recognition of hazardous drinking. This is perhaps surprising, but it relates to primary care. It relates to visits to the urgent care. It relates to visits to emergency rooms. It relates to obstetric and gynecological visits in women. These are opportunities when patients who are drinking to excess might have that brought to their attention and a suggestion about how to address it made to them. And that's not happening. And I have entitled this slide, that we're going to see some rather wordy black and white slides. I apologize for this, but I've called this a dual paradox. For the first sentence refers to what I was just saying, that patients with AUD have many interactions with health professionals at which AUD is either unrecognized or dismissed. But also ALD itself is detected at later stages than other liver diseases. So we are failing to recognize the early stages of AUD and we're failing to recognize the early stages of ALD, hence the dual paradox. The second pitfall is when a problem with drinking is identified, there's lack of referral to specialists in care of patients with alcohol use disorder. And this is shown in, again, another very black and white slide here, but a very interesting study from Dr. Rogal in the VA. It's a VA study. The VA being valuable here because first of all, it's got great numbers, great data collection, and it's also got very well-established treatment protocols for mental health. And in this study, approximately 100,000 veterans with cirrhosis were canvassed and they found that they had just under 36,000 in whom an index diagnosis of AUD was made. And then they looked to see what was the reaction in the management of these patients to the recognition of alcohol use disorder in these patients with cirrhosis. And you can see that only 14% were referred for treatment, even though, as I say, the VA has processes for providing treatment that are greater than in many other medical models in the United States. And of that treatment was almost invariably behavioral. Very little pharmacotherapy was offered to these patients. And in keeping with what we just heard from Harvard, they also found that the treatment of AUD in these patients with alcohol-related liver disease led to a reduction in incidence of hepatic decompensation and a significant decrease in long-term all-cause mortality. So there appears to be a connection between introducing treatment for alcohol use disorder in patients with alcohol-related liver disease and seeing a benefit in the liver disease. So this relates to the third pitfall, the underutilization of pharmacotherapy or psychotherapy, for that matter, for AUD by gastroenterologists and hepatologists. We, because that's who we are, are not good about initiating the treatment of alcohol use disorder in these patients or sending the patients for attention. And we have data on that, and it comes from the ASLD Alcohol SIG, the SIG that has put on this meeting. So this is a very nice paper by Jean Im, Jessica Mellinger, and John Rice. And so it allows me to put in a plug for joining the SIG. Look, not only do you get great webinars, an opportunity to enhance your knowledge, but you have an opportunity to take part in interesting studies that advance the field. And in this study, 408 providers, physicians and physician trainees, the majority practicing in a hospital in a transplant program, were asked about their practice behaviors with regard to AUD. And three quarters reported low levels of education in addiction medicine. 39% do not routinely refer ALD patients with AUD for behavioral care. 50% lack knowledge about the medicines that might work. This is a source of considerable distress to the people who work in the NIAAA, because they say there are medicines that work, and yet they're not even being used. And three quarters of the respondents had never prescribed a pharmacotherapeutic agent for alcohol use disorder. And they all said they'd like more training. So the conclusion is we need more training. So today is a response in a way to that survey. So that's the why, now the how. How to make this a reality, to improve your role in your clinic in managing alcohol use disorder in your patients with ALD. The first is recognizing it. And as I mentioned, these patients have many interactions with medical care which fail to recognize their drinking problem. And so I'm not knowing exactly who's on our call today, but some of you may be in primary care circumstances. That's the ideal place. So the Audit C questionnaire is a good, simple introduction. During the last 12 months, how often did you usually drink any kind of drink containing alcohol? If they say no, you don't even need to go to the second two questions. And then two questions about quantity of use. How many alcohol drinks did you have in a typical day when you drank? How often do you have five or more drinks on one occasion? And there's a point scoring system for this, which is useful, but I would even say, if you don't remember the point score, just remember the questions. They're really a structure to enable you start to talk about this. And the NIAAA, whom I've mentioned, have put out this nice little handout, and here's the link to it. And it's the sort of thing you could carry around in your pocket. And it says, what you're trying to do is raise the subject. So the Audit C questions raise the subject. And then from there on, you'd like to provide feedback, enhance motivation, and negotiate a plan. And this is all in the SBIRT model. And you can see if you detect a low risk, positive reinforcement and advice starts. But if you have a higher risk, a referral to an alcohol use treatment center is advisable. And finding out links to your place of work where you can find people with that expertise is a good thing to do. And there are brief intervention steps here, which you can read at your leisure, but they help you address the question, work out, get the patient engaged as to what's going on, have non-directional counseling and negotiating a plan. So while you may not have the level of skill and expertise of somebody who's gone through formal training and counseling, and those professionals are useful. Sorry, I'm on call, so I'm gonna have to say I can't take that. While those persons are very useful as part of a team, you can make the start yourself with these sorts of steps. I was asked to say something about biomarkers. One could talk a lot more than I'm going to about them. As you can see, there are some that are directly related to ethanol metabolism and some that are indirect. We use the indirect ones all the time, looking at liver chemistries and mean cell volume, and they are sensitive without being very specific. But the three that are really getting, might be in terms of practice are ethanol, ethanol can be measured in many ways, including a breathalyzer, but that gives very recent drinking. And then ethyl glucuronide in urine is looking at drinking in the last three days. And phosphatidyl ethanol is a very useful test, which is not excessively sensitive, but is highly specific for drinking in the last 28 days. And I have a further slide in that, where's it come from? It's the result of a chemical reaction between ethanol and phosphatidylcholine present in the membranes of red cells. It has a half-life of approximately four days. And as I mentioned, it is, as somebody said, it's like the hemoglobin A1C of alcohol use. It seems to be highly specific, so we're not expecting any false positives. And it's been set at a level of detection, so that modest amounts of alcohol are not necessarily going to trigger a positive result. So two or more drinks on average a day. So it's a useful test that is not going to be positive all the time. When it's positive, it's meaningful. It's also semi-quantitative. So if it's 600 one week, and 400 the next week, and 100 the next week, it's likely that person has stopped drinking, and that decay is indicative of attempting to establish sobriety. Finally, I just want to tell you about our Digestive Health Center, which has now got an alcohol-related liver disease, alcohol use disorder clinic. And that's a thing that you might consider trying to establish in your center. And we don't take credit for this. This is modeled on the clinic at the University of Michigan. And one of its progenitors, Dr. Winder, is going to speak immediately afterwards. The hepatologist is Jessica Mellinger. Jessica was a resident and a chief resident here at the University of Wisconsin. So we see her as one of our own, and she's been very helpful in helping us set up this clinic. It's the hepatologist who's leading it is my colleague, Rita German. And the first thing she did was find a partner in addiction medicine, and that's Randy Brown. And with Drs. Brown and German as the core faculty, they then built the necessary partnerships to make this happen, including the health system administration. This doesn't make money. It doesn't cost a lot of money, but it costs some money. It's a quality improvement, not a revenue generator. So convincing the health system that this is a good thing to do, and they were very successful at doing that. They got assistance from nursing, pharmacy, social work, and we have a health psychologist just lateral to us. So this is the network that's necessary. This is the goals of the clinic here, provide and connect patients with alcohol-associated liver disease, with alcohol counseling and pharmacotherapy to enable them achieve alcohol cessation. And at the same time, we want to optimize management of the complications of cirrhosis. So that's that point where you saw the improvement, that green line going from decompensation to compensation, going from cirrhosis back to something less than cirrhosis. We want to improve the quality of life. And then this is a very important teaching center. We realize that a clinic like this is not going to be able to cover all our patients, but by teaching doctors, APPs, and nurses in the clinic, we feel we're providing the necessary infrastructure to spread out through the state. These are the patients we're treating, patients with ALD or acute alcohol-associated hepatitis, not eligible for liver transplantation. So we're not cutting into the transplant practice. That's really a tactical issue to just decide where our efforts would be best placed at the moment. The patients have to have been drinking within the last six months, and they have to be willing to join the clinic. I've just been rounding and just been speaking to such a patient who initially yesterday, when admitted with acute alcohol intoxication, and now was put on the CEWA protocol and all that, but today is much better. Yesterday, didn't want to hear about this. Today said they would join our clinic. So we're going to have that patient come to this clinic. That patient is already cirrhotic. So this is my outline again. Why? Why optimize the clinic's role? First of all, patients with AUD and ALD are not being recognized early enough in the course of their disease for either disorder, and they're not receiving appropriate treatment for AUD. And the treatment requires expertise, commitment, and support, but not only does it help the AUD, it also helps ALD. And then the how, the key is increasing awareness and skill levels of practitioners at all levels in the care chain. That's what I'm referring to, primary care, all the subspecialties right up into the hepatology clinic. So there's opportunities for improvement at all levels. And one way of trying to improve the development of this higher skill level across many practitioners is the multidisciplinary ALD-AUD clinic. And I think it has an important role. And we're very grateful to the University of Michigan for helping us set up our clinic. And this is a good point for me to stop here. We have the terrace looking over Lake Mendota. We're hoping to see sunny days like this in the near future here in Madison. And once again, thank you to Suthat and Brian for the opportunity to speak, and I'm looking very much forward to Scott's presentation. Thank you so much, Michael, for a great talk and summary. And this is a nice talk that lead us to the last speaker for today is Dr. Gerald Scott Winder, who will be talking to us about the pharmacotherapy to treat alcohol use disorder and also more intensive referral treatments that can be useful for patients with alcohol use disorder and liver diseases. So Dr. Winder, in fact, is not a hepatologist as might have been alluded to, he's a psychiatrist and a clinical associate professor at the Department of Psychiatry, Surgery, and Neurology at the University of Michigan. As a consultant, he has co-founded specialty clinics that embedded in organ transplantation, neurology, and also hepatology, working on these interprofessional teams that providing this integrated psychiatry and medical care for patients with AUD. So we look forward to your talk, Scott. Thanks to Suthat and thanks to Brian for the invitation. It's an absolute honor to be alongside Dr. Lucy, who has an enormous legacy here at the University of Michigan and throughout the world in terms of his expertise. And I got a chance to meet Liz in Vancouver and just really impressed by her acumen and scholarship. It's great to be alongside her again, virtually. And I'm just really grateful for the AASLD. It's such a benefit selfishly to be associated with hepatologists and transplant surgeons and amazing APPs who train me and make me a better physician to take better care of these patients who deserve better than what we're doing. So I'm just grateful for this invitation. I just, I feel like I have the best job to be able to be a psychiatrist and then to get to travel in these amazing places alongside all of you all. I do have some financial disclosures, but none of them are relevant to today's talk. I would like to zoom in a little bit on AUD pharmacotherapy. I'll move briskly. There's a lot here and I wanna be mindful of time. And we'll talk about some on-label and off-label medications. Again, a little bit of a US-centric view, which you'll forgive me for. And I would like to say something about psychotherapy, which unfortunately gets short shrift in biomedical spheres. And I'd like us all to be a little bit more open and enthusiastic about psychotherapy. And then we'll talk a little bit more about some of the higher levels of care that often and frankly cannot inhabit the same space as a hepatology clinic. And again, on the coattails of Dr. Lucy's wonderful talk, I would like to make a plug again for integrated care as a gold standard, while it's not feasible for all of us all at once. A little bit of a soapbox. This is an archipelago of care that these patients encounter. And it's unfortunate. It's very, very bewildering for them. And I think we need to awaken some sympathy and empathy for what it's like for people to not only have advanced liver disease and to be alarmed in a very real sense about their own mortality, and then sometimes just get shuttled off into some community provider that has nothing to do with their liver care. And I always show this slide because I think that there are dangerous gaps and disconnections that are frankly unacceptable as they currently are. We've got to be able to take better care of these patients. There are dangerous gaps between addiction and psych and liver clinics. We should not be satisfied with this. And it's so gratifying to see the AASLD bring talks like this onto this level of platform and to support efforts to build interprofessionalism. I, again, I would put myself under this microscope. I want to be able to read a comprehensive metabolic panel and pick up some of the guidance of my hepatology and surgery colleagues. Still the patients cannot tell where their alcohol care and their liver care begin and end. I think that's a goal we can achieve, but we've got to think, practice, collaborate, and train with a higher degree of interprofessionalism. And then I'll get off my soap box. So let's dive right in. So these are newer data from Dr. Robillet from a VA sample in the panel on the right here. It's important, let's say that these alcohol use disorder medications are not approved for use in alcohol-related liver disease. ALD patients are traditionally excluded from alcohol drug trials. And you saw Dr. Lucy quote some of the data from Dr. Rogel and Dr. Mellinger has also published this, that it's extremely and unacceptably low how few of these people get access to specialty medications and psychotherapy. But Dr. Robillet's work on the right-hand side of your screen shows that this is changing over time. Medication-assisted therapy for alcohol use disorder is improving within this VA sample. And I think that trend, we can extrapolate broader from that. And we care about this, as you'll see in the next slide, because by administering these medications, we save costs, it's effective in reducing hepatic decompensation, and it's not just medicines. Also the behavioral treatment, as we'll see, is also important. So also from Dr. Robillet, and these are brand new data from hepatology communications, but you see that just generally the black line is people who did receive naltrexone and acamprosate, and the gray line is people who didn't. And you see a statistically different trajectory in terms of their survival. And it also matters how long they stay on these medicines. If you stay on them more than three months, you separate with statistical significance from people who were left in three months, and of course, from people who didn't take them at all. So it's a good primer. It's a good reminder that this isn't idle prescribing, and it makes a difference. If a hepatologist who really doesn't understand addiction has the courage and the confidence in prescribing these medicines that are a little bit at the fringes of our expertise. So I'm not gonna linger on this, because this is not something that hepatology uses a lot. I have a patient who got a liver transplant because her liver was necrotic from disulfiram. So this is a medicine that is used in the non-ALD population. It does have this hepatotoxic side effect profile. I did list some general guidelines from the literature there about how to monitor LFTs, but for a hepatology audience, it bears mentioning in theory, but we often don't use it. In our multidisciplinary ALD clinic that Dr. Lucy mentioned, we never, ever prescribe this medicine. We take people off of it to reduce the risk. It does have a use, just as a kind of trivia bit, for cocaine use disorder unrelated to its dehydrogenase inhibition. Now, Trexone is a fascinating medicine, and we love it, and we use it all the time. It does antagonize the mu opioid receptor in the human body. It is contraindicated with opioids. For that reason, with our medical population, we tend not to use the injectable 30-day depo formulation. Makes us a little uncomfortable about what would happen if they had some problems. You can't get the medicine out once it's in their muscle. And it gives us a little bit more flexibility, our colleagues, to stop the drug if pain medication or other sedation needs arise in a medically sick population. We don't give this during hepatitis encounters or when the liver is otherwise severely damaged. You can see the dosing there, and you do see that it is supported by a meta-analysis, which I cite at the bottom of the screen, a robust cohort that shows that this medicine reduces relapse to any drinking and binge drinking in the general population. Very few data in comparison for the liver population to the general population. Most of what I will cite and talk to you about today is not ALD data. It is a general population data. So there's caveats there. Acamprol, acamprosate is also a wonderful medicine. We don't really understand a lot of how it works, but it does antagonize the glutamate receptors, the NMDA receptors, many of them in the frontal lobes of the brain, which reduces neuronal hyperexcitability, which is likely brought about from chronic alcohol exposure. It has an unfortunate suspicious formulation of 666 milligrams three times a day. So it is onerous for a TID dose, but in meta-analysis, it does reduce the risk of abstinent patients returning to any drinking. That's a little bit of a pearl there. In the addiction literature, as best I understand it, acamprol has a little bit more bigger effect size for people already established in their abstinence, but naltrexone might be useful for people actively drinking who can't really get that early abstinence. And so we make some strategic decisions in our multidisciplinary clinic along those lines. It also promotes total abstinence duration. Other studies say that it doesn't separate from placebo. And again, with a lot of CNS medications, we see this. But when you're taking care of people, who cares if it's placebo or not, honestly. We care in drug trials, we want to be confident and encourage them and suggest to them ethically that this is going to work for them. Gabapentin is wonderful. We use it all the time. We're not sure why it works in alcohol use disorder, but of course, alcohol is GABAergic and so is gabapentin by name. You see there a cited meta-analysis of seven randomized control trials. And you see that gabapentin did reduce heavy drinking days, but not some of those other outcomes. The dose varies. We tend to shoot for, barring renal function problems, renal insufficiency or dialysis, we shoot for about 600 milligrams three times a day. And we do keep patients on this for a long period of time, though many studies don't follow them for longer than three to four months. But we love it for alcohol use disorder comorbidities. I'm aware of hospitals that try and manage all mild alcohol withdrawal with gabapentin, trying to avoid the pit of over-medication with lorazepam. We use it off-label for anxiety, certainly has application for neuropathy, which calcineurin inhibitors, diabetes, alcohol itself, and certainly it's off-label in the sleep literature for insomnia. We love this drug. 10% of people will have some lower extremity edema. We have seen that. So with patients who have new onset worsening edema, you have to be careful with gabapentin. We've hit that snag at least 10 or 20 times prescribing this medicine as avidly as we do. Baclofen is kind of a rockstar. The reason for this is it's supported in ALD with a randomized control trial published in the Lancet in 2007 by Dr. Adolorado. 10 milligrams TID. I think hepatologists love this medicine for that reason. I don't disagree. The problem is, is it has a lot of sedation. We cannot get people to stay on this medicine. I would say half of them discontinue it. So I think we should feel confident as long as they don't have really bad hepatic encephalopathy and kidneys are okay. We should be prescribing this, but we have just run into some problems with sedation that we don't see with gabapentin. So we like this. I don't mean to talk down about it, but anecdotally we struggle with it. And then Topamax, same type of thing. It is sedating and it gets nicknamed Dopamax sometimes by the neurologist because it has this really stereotypical idiosyncratic problem with word finding that patients can have a problem with and encephalopathic patients don't do well on this, but it is supported by data in alcohol use disorder. We've had some great instances where a patient had to lose weight just to get to transplant surgery. And we kept them sober with topiramate and facilitated their weight loss. We don't prescribe this to anybody with a history of renal stones. So that's just like a deluge of information about the drugs. And I apologize for the brisk nature of that, but I don't want to give short shrift to psychotherapy. I don't have time to go through these in detail the way they deserve, but they must be in our minds as underutilized and non-pharmacologic interventions that often outperform psychopharmacology. The top level there have more data behind them in liver patients than the bottom row there. And we've written about this if you want to read more about each of these as relevant to liver patients. But again, I want these to be in everybody's mind as important. And they're studied. Psychotherapy and AUD's pharmacology are studied together in the general population. This is a quintessential example of that. This is the combined study from Dr. Anton from 2006. It's a very, very complicated and well-run and elegant study trying to look at the interaction between medication management, treatment as usual, medication management, and what's called in this study combined behavioral intervention, which had CBT and AA visits. And the crux of it is, I'll have to go quickly through this, is that naltrexone tended to perform better in combination with placebo and medical management and CBI, it did outperform the other interventions, including Camprol. And the cool thing is here, it's not a formula that just a single formula, there's many prongs and possibilities to get people to stop drinking. There were good outcomes in the study. It's reasonable and worthwhile to treat patients with their alcohol use disorder, but naltrexone outperformed it. And there was no data to combine naltrexone with a camprosate. That didn't bear out in this study either. So a compelling study. I'll move quickly through here. Here's another one by Dr. Anton the year before, also showing that when you combine naltrexone with cognitive behavioral therapy and with motivational enhancement therapy, which is a more kind of structured and deliberate channeling of motivational interviewing, motivational interviewing is just a communication paradigm. It's like a high yield toolbox for any, any clinician. I would encourage you to read that book. It's Miller and Rolnick. It's available on Amazon. It's in its third edition. It's like scripture for any of this. But when you see naltrexone plus therapy, you see how that outperforms the placebo groups. So again, this is really what we aim for in our multidisciplinary clinic. So I don't have much time left. I need to hurry up a little bit. I am gonna skip through this. So this is the American Society for Addiction Medicine. I want you all to see like the levels ideally that we look at in the field of addiction to try and help people to understand and place them in an appropriate tier of care. This goes from where you all help us, which is those top two, intoxication and withdrawal and also their biomedical conditions. But then there's a whole kind of panorama of emotional and psychological elements, like how ready they are to change and what psychosocial factors might put them at risk to relapse. What is it about their social ecology and their relationship integrity that might put them at risk either to relapse or might be protective. And it's a pretty sophisticated, subjective gauge of all of these variables when we assign a level of care. And these are the other levels of care that you often see. Dr. Lucy gave a great summary of SBIRT, which we rely on hepatology and primary care to do for prevention and early detection. Frankly, these patients often will listen to a hepatologist or a primary care or a general interest before they would listen to us. So that is not an idle step here. But then when you get into outpatient psychotherapy, intensive outpatient or partial hospitalization, these are like day programs, two to four weeks, several hours a day, patient goes home and sleeps in their own bed, comes back, residential rehabilitation and transitional housing. These are tiers of care that are often invisible to patients in liver clinic, but they are important, robust resources, even though we don't have enough, in the community that our ALD patients need to access. And of course, we're all quite familiar with the medical inpatient. Some of the data that I will cite momentarily to finish my talk, cite some of these tiers of care that are not affiliated with the liver center who's publishing the data. What I mean is it doesn't necessarily matter if it's an integrated clinic like Dr. Lucy described, or it's just a loosely affiliated resource where it's not necessarily integrated clinic. And that's the point of what we have proposed here. This was published last year. We are contending that there is a sliding scale of different levels of affiliation between addiction and psych and medicine and liver. And so it's not one size fits all. I think that's a theme here, that there are ways, I won't read this to you. There are ascending in various ways creatively where we can build care models that serve the patients well and improve outcomes. And this has been published. So we have published early data in our integrated clinic where healthcare utilization goes down. When you compare the six months before the patient meets us to the six months after they meet us. And Dr. Lucy cited one of his other papers. I won't read all this to you. They have this really great liver centric consultation service, proactive consultation. They've gone out into the hospital on general medical services where the patients didn't even have any liver symptoms. And they using elastography primarily found new liver disease, advanced liver disease. And then 30% of the patients that they saw. And not only that, the show rate of the patients after they got this new information about their liver that they had no idea about, the show rate in the outpatient ALD clinic was better than the baseline show rate. 44% for the people caught in the hospital versus 27%. And then up in Liz's neck of the woods, this is the Toronto group, a fantastic study showing that you can take really high risk ALD patients and you can transplant them. And this pilot program is notable here because it had AUD therapy integrated into the center, but also coordinated loosely outside of the center. Again, there's some flexibility here depending on the types of relationships and the champions we have and where we are and what resources we have. And then this is great from Dr. Singal who I think is on this call. And I love reading his data to him, but this is a great study where it shows that specialty AUD intervention just alongside liver disease trends toward helping people stay abstinent, trends toward helping people stay sober and statistically significantly reduced patient mortality. It is worth doing this, even though it is hard. However, we can link this addiction treatment alongside liver care. And then within liver transplant recipients, these were statistically significant results. People relapsed less and they died less often when they got this integrated addiction care. So I'm really glad for this opportunity to speak. Sorry for the verbal mania here. I wanted to get through all this. Thank you again for the invitation. I appreciate it. Thank you. Okay, so I'd like to thank our speakers. These were some wonderful talks and a lot of content. We'll have a brief couple of minutes for questions and we do have some already. And one, I was thinking about myself and I think we've all encountered this. We have effective therapies, we've learned this, but we meet a patient and we offer them say pharmacotherapy, but they say that they're fine just on their own. Kind of what is your approach and how do you motivate them to kind of engage in therapy, whether it be pharmacotherapy or referral to our addiction specialists? I don't know if Scott, you wanna take this, Dr. Winder, you wanna take this question first? Sure, yeah, I didn't wanna jump in after my, everybody's had enough, they're saturated. So a couple of things, Brian. One is to earn their trust. It sounds like a kindergarten thing to say, but there's really no substitute for that. If you're gonna make a recommendation that's basically preventative and they can Google it, you need to have their trust. We get a lot of mileage out of analogies and metaphors. One of the high yield ones we use is to link it to kind of preventative care with hypertension and diabetes. People tend to be able to think early in their recovery, especially when their liver is sick, they think medically more than psychologically. So it makes sense to people to stay on an antihypertensive to manage their blood pressure. And even if the blood pressure is normal, they understand that their disease isn't cured. When you run their mind through that thinking and then come back to the fact that you're here because drinking is out of control, you can't anticipate when you drink, it isn't magic. It creates a buffer between you and a relapse. It's not pretty, there's other stuff we've gotta do. Let's get real about this. But you've got an amazing hepatologist, Dr. Mellinger, Dr. Lucy here to watch you. Let's do this, let's help you to get sober. That kind of like encapsulated optimism, education, trust and connection to other conditions, they probably understand a little bit better, has been a potent mix for us. It sounds like trust and persistence is key here. So we had another question, which I think is really important is that, why are we not seeing large scale randomized clinical trials for alcohol use disorder, pharmacotherapies in patients with liver disease? I don't know if Dr. Lucy, you want to address this question? I think somebody has to pay for them. The medications that Scott listed are all relatively old. And so they are often available in generic form. So I think that'll be the key. The NIAAA would be the place where we'll return to for support. But, and so I think that that's the key is it's, large trials are difficult to do and they're expensive, but they are doable. We also have to accept that have reasonable expectations of outcome. I think one of the hard parts of the whole field is deciding what the end points that we're interested in. If we're interested in improvements in liver health on the basis of administration of medications or from psychotherapy or a combination of the two for alcohol use disorder, you get into quite complicated statistical calculations to try to work out the numbers that you need to recruit because you're actually looking for the consequence of a consequence. You want them to stop drinking and then see the benefit of stopping drinking. And so that's quite a difficult thing to do. There are innovative ways of designing trials that would be helpful in this regard. But I think that's, they're the key, the issues of design and issues of who supports. But there's a clear need. Yeah. So, you know, we are running late, but I did have one final question. And, you know, Liz, your presentation, this term of disease prestige really struck me. And, you know, I don't know how many times I've heard, you know, for example, you know, hepatologists talking about their patients with PSC and how they'll never get transplant because of, you know, patients with alcohol and they didn't choose this life. So, you know, even in the transplant world, there's even talks because of the surge of transplants for alcohol about how do we stem these floodgates? So kind of what is your response to that and how do you approach these conversations even with our colleagues? Well, I feel like you asked me the hardest question. I mean, yeah. Well, I think it goes back to a conversation around health equity. And I think it goes back to just talking about individuals as people. Like, and I think that, you know, I think that everyone deserves care. And I think that a lot of our colleagues, I think part of it is, and I think for us here and especially for myself here, like I work in a public payer institution. So, you know, like I think that there is some, I mean, it is not easy to actually have that conversation because it is fraught with controversy. But I think it's really just coming down to the principles of, you know, I think recognizing that, you know, we do need to, and I think that goes back to the broader conversation around also breaking down stigma also as well. Because the reason why these conversations are happening is also what we are perceiving as deserving. And then so, and I think that that's really the base of it. And I think that's why we also today as a group in terms of our webinar had also, had wanted to bring in the conversation around stigma. Because if we don't actually talk about it in that sense, and if we don't actually just talk about people being deserving of care in your, regardless of whatever disease etiology it is, we will never actually get past that point. And then, so I think that I do really applaud ASLD and also the organizers here, as well as our group here about being able to have these conversations. And hopefully we continue to have these conversations altogether. Yeah. So, you know, to conclude, you know, I really like to thank our speakers. It was such a fantastic webinar for their talks and really for ASLD for supporting this webinar. I've learned a lot myself and hope that everyone can walk away from this webinar with tools that they can apply themselves now and their clinic to help their patients. So thank you for joining. We'll now conclude this webinar. Thank you.

ASLD webinar

optimizing liver clinics

alcohol use disorder

patients with liver disease

disparities

access to treatment

collaboration with providers

screening for alcohol use disorder

counseling techniques

integrated care