Well, I'm going to say welcome to our one attendee. Thank you so much. So I'm Laura Nagy. I'm an investigator in the area of alcohol-associated liver disease with innate immunity. And today we have a session entitled Shared Care, the Integration of Alcohol-Associated Organ Damage and Psychiatric Care. And our first speaker is Arun Sanyal from Virginia Commonwealth University. The title of his talk is Introduction to Alcohol-Induced End Organ Disease. Thanks, Laura. Do you want to introduce yourself? Oh, I'm Catherine Miller. I'm from Seattle. I'm a psychiatrist. OK, great. Thanks for coming. Yeah, thank you so much. No, no, no, it makes the trip from the East Coast worth it. So I am very, very grateful that you actually showed up. Although it was good to catch up with Mandana earlier today as well. So my job today is to talk about end organ damage. And I was really unsure sort of what the audience was, how much what their background was, et cetera. So if it's too simple, I apologize. So here are my disclosures. So I think at this meeting, everybody knows that in the United States we have a big problem with alcohol consumption. And there's a very large segment of the population that consumes alcohol. But more than that, there's a large segment of the population that engages in heavy drinking and in binge drinking. And what that computes to nationally for society is 140,000 deaths annually and reduction of a lifespan by 26 years. And it kills one in five adults between the ages of 20 and 49 and involves an annual cost of almost $250 billion. Now much of this is actually linked to the impact of alcohol on end organs. And as shown over here, the liver, the heart, brain, pancreas, even kidneys, virtually every organ in the body is impacted by alcohol. I'm going to talk only about, given the limitations of time, about the principal organs that contribute to the burden of end stage disease and health care resources and health care resource utilization. So I'm going to divide my talk into three parts. Just very few slides on basic mechanisms of alcohol-induced end organ damage. Then a primer, which is the main part of the talk, on the clinical spectrum of end organ disease. And then some key takeaways that if you are in the behavioral health sciences field, what can you integrate and take back to your practices? So one of the things that happens very early on when we start consuming alcohol is that the intestinal microbiome changes. And this is a study that we published a couple of years ago showing that there are very clearly established changes in the microbiome, even in the absence of end organ disease. And this is a comparison of healthy individuals and heavy drinking controls. There's, of course, a large body of literature connecting the dots between changes in the microbiome and its impact on the body. And this involves impairment of the gut barrier function, neurogenic signaling from the intestine to the brain, local and systemic activation of inflammation through activation of the innate immune system, and more recently, this idea of acceleration of aging-related inflammation, which is also known as inflammation, that turns out to be an important part of many chronic non-communicable diseases across multiple end organs, where you have an accelerated program of aging. And the organs sort of get inflamed and scarred down before their time. Now, this looks like a complicated slide, but it's actually not. So if I walk you from the top to the bottom, ethanol metabolism leads to oxidative stress. Oxidative stress leads to an amplification of a variety of things that happen at a cellular level, from epigenetic changes, lipid peroxidation of membranes, metabolic stress, dysfunction of proteasome, which is the cell's toilet. And all of this contributes to cell stress, which, if severe enough, will kill the cell. At the same time, oxidative stress contributes to systemic inflammation. So all of this compounds the inflammatory state within the end organ. And at the same time, as you can see on the far right, that the ethanol can lead to acetaldehyde, which also leads to inflammation, independent of everything else I've shown you. So you have multiple sort of pathways that converge on inflammation. Inflammation drives fibrosis and sets up a pro-oncogenic milieu. Now, this is further compounded by the fact that we live at a time where 2 3rds of the population is overweight or obese. And at the same time, they're also consuming alcohol at various rates. So there's an overlay of the underlying metabolic biology of obesity, diabetes, fatty liver disease, non-alcoholic fatty liver disease, with what is happening due to alcohol. And one of the things that happens where they overlap is with this idea of an accelerated aging program. There's now a huge amount of literature showing that there is a back and forth between the intestine and the liver, back and forth between the intestine and the brain, back and forth between the intestine and adipose tissue, all of which are controlled by what are called clock genes. And dysregulation of this crosstalk is an early and a central theme that is linked to obesity and nutritional excess and leads to an accelerated program of inflammation, as shown on the right, where with constant overnutrition, you tend to overcompensate and produce chronic inflammation, which then can lead to fibrosis. Now, moving on to something we actually see in our clinics. One of the key things to remember and one of the important organs that's affected by alcohol is the liver. Of course, I have a biased view as a hepatologist. So mortality due to alcohol-related liver disease is increasing, and particularly in women, and particularly in younger women. So this is of great concern and actually a real public health problem. Now, when you think about the natural course of alcohol associated liver disease, it follows a certain cascade where sustained heavy alcohol consumption leads to initially relatively asymptomatic fatty liver or something we call steatohepatitis. We'll go through all this step by step, which can progress to cirrhosis. Once you get cirrhosis, you can get what's called decompensation, which basically are complications of cirrhosis, which set up the cascade that leads to death. Now, somewhere along the way, the clinical course can be interrupted by these bouts of acute jaundice that develop, and this is called alcoholic hepatitis. And this may resolve, or it may progress to cirrhosis, or it may kill the patient. And so you can get also directly from sustained heavy, at least theoretically, from heavy alcohol consumption to acute alcoholic hepatitis and decompensation. But more likely, most of those patients have underlying fatty liver and steatohepatitis before they get there. So let's start at the top and think about fatty liver. Some of the key things to remember is that even a single binge can lead to a fatty liver. The good news is the fat comes in very quickly and leaves the liver very quickly. Back in the late 70s, there were a series of experiments where medical students were taken out and given a six-pack. And then they were biopsied the next 72 hours later, and they all had a fatty liver. Then six weeks later, they all were given another liver biopsy, two liver biopsies in six weeks. And they had all cleared their fat from their liver. Of course, we'll never do that study now, but that's how it was back then. But alcoholic-induced fatty liver is asymptomatic and reversible. But over long periods of time, when you're engaged in very heavy alcohol consumption, you're now using alcohol as your primary source of energy. And so you essentially create a state of malnutrition because alcohol constitutes empty calories, and they really don't have any nutritional value. Now, moving on from fatty liver to steatohepatitis, this is a histological entity where you get, I don't know if you can see this very well on your screen, but if you look on the left panel, within some of these cells, you see this clumped up, very pink material. These are called malory-dength bodies. And in the center, you're seeing this blue stuff, which is all scar tissue around the central vein in the liver. And this can lead to progressive bands of scar tissue, which can eventually lead to cirrhosis. So these are hallmark lesions of alcohol-associated steatohepatitis. Now, we know from non-alcoholic fatty liver disease, we don't really have high-quality data in the alcoholic steatohepatitis field, that the amount of scar tissue is the critical determinant of outcomes. So the more scarred your liver is, the more it's connected to the likelihood of decompensation and all-cause mortality. But given the overlap that I showed you between obesity and alcohol, I think it's highly likely that the fibrosis is still the most important determinant of outcome. So coming back to this asymptomatic or mildly symptomatic patient with fatty liver or steatohepatitis, what we know is that many patients with heavy alcohol use have it. They may be asymptomatic. There's an interaction with obesity, insulin resistance. Patients can be symptomatic or not, and fibrosis stage is a key determinant. So the clinical message in an addiction medicine clinic is that in those with risky drinking behavior, it's important to rule out clinically significant fibrosis. That is when enough scar tissue has developed that puts the patient at a liver-related risk beyond the broader risk associated with risky drinking. And similarly, in internal medicine clinics, we need to ask about risky drinking and then follow through, particularly if there are risk factors also from a metabolic side in the form of obesity, diabetes, hypertension, et cetera. So what should you do? One time, check a CBC with platelets and a hepatic panel. Why? Because you can compute something called a FIB4 score, which is based on age, AST, ALT, and platelets. And so we initially published, Richard Sterling from our group actually published this initially in the HIV space, and we published it in non-alcoholic fatty liver disease, and more recently have shown that it actually predicts mortality. And it is in all of the practice guidelines for chronic liver disease where it's a starting step. And the reason being, if your FIB4 is less than 1.3, you will basically have, your risk of actually having an end-organ outcome is extremely low. But on the other hand, if it is more than 1.3, then you need to pay more attention. So essentially, that tells us that what you can do tomorrow is check the FIB4. If the FIB4 is less than 1.3, just focus on the behavioral aspect. If it's more than 1.3, that tells you there's already ongoing end-organ damage. Now in the long term, this can lead to cirrhosis, right? So progression to cirrhosis reflects worsened clinical status, and so reduced progression to cirrhosis could be a clinically meaningful goal of therapy in the clinic. Many patients will have metabolic disease drivers. This is a repeated theme that I keep talking about. And continued alcohol consumption after development of cirrhosis accelerates the time to outcome. So once you get to cirrhosis, you actually really absolutely have to stop. So in the addiction space, we frequently talk about number of drinking days, number of heavy drinking days. Once you start scarring your end-organ down, you have to stop. Your body has already told you that it has reached its lifetime capacity for handling this stuff. What we don't know, however, are the proportion of people who are progressing, time course of progression. We really need more holistic models, and the natural history of this chronic alcoholic liver disease, I think, needs to be redefined. Finally, then we talk about these episodes when the patient suddenly becomes jaundiced. And there are NIAAA guidelines on recommendations that we came up with about defining this alcoholic hepatitis clinical syndrome. So you can define it by biopsy, but many of those people are asymptomatic. So this is a clinical definition where suddenly the patient becomes jaundiced. And much of this, again, links back to the gut microbiome, the release of endotoxins, and then the release of cytokines within the liver that induces jaundice. So the liver-related take-home messages. Liver disease is common, and increasing common comorbidity in patients with AUD. In asymptomatic patients with alcohol-induced disease, especially in the presence of obesity, type 2 diabetes, the fibrosis stage is a key determinant of outcomes. Check a FIB4 once. You can Google, if you Google FIB4, the calculator will pop up. You put in the AHA-STLT platelet. If it is less than 1.3, focus on AUD management. If it's more than 1.3, in addition to AUD care, consider a referral to GI hepatology for additional testing and management. Moving on to other organs. Cardiovascular, this is a big deal, because there are a number of cardiovascular risks from hypertension, particularly with binge drinking, heavy alcohol use, strokes, atrial fibrillation, cardiomyopathies. And the more you drink, the greater is the risk. So the clinical takeaways are that besides the AUD care, you have to counsel them about the end organ, the risk of end organ disease. And certainly some of the clues that there might be something going on with the cardiovascular system is if they have high uncontrolled blood pressure, history of syncope, or presyncope, or shortness of breath. The next organ to talk about is the pancreas, where under sort of one of the effects of alcohol is co-localization of pancreatic enzymes with lysosomes, so that the pancreatic enzymes that we need to digest food in the lumen of the intestine get activated in the pancreas itself, which starts autodigesting and leads to acute pancreatitis. But it can also occur at a slow, smoldering pace and lead to chronic pancreatitis. So pretty much everyone with alcohol-induced pancreatitis that's clinically obvious already has chronic pancreatitis. And the course is interspersed with bouts of acute pancreatitis, which can be life-threatening. So chronic pancreatitis can lead to exocrine insufficiency, more malnutrition, maldigestion, and is a very common cause of severe chronic abdominal pain and can also increase the risk of diabetes. And in those consuming heavy levels of alcohol can increase the risk of pancreatic cancer. With respect to the brain, there's a whole spectrum of neurologic disorders linked to alcohol from peripheral neuropathy, Wernicke's encephalopathy, Korsakoff's, dementia, cerebellar ataxia, and withdrawal. And of course, they are both structural and they are functional changes in the brain and within the peripheral nervous system that's linked to this. Alcohol is also a major driver of cancer. So the linkage between alcohol, oral, and esophageal cancer, very well established. Something that is also well established, people don't talk about it, is the link between alcohol and breast cancer. And there's data now that even one drink per day on a regular basis, not occasionally, but on a regular basis does have a positive impact or actually a bad negative impact on the patient in terms of the risk of breast cancer. And of course, with all these other cancers. So alcohol as a cause of cancer, as a preventable cause of cancer, is really an important piece of the larger clinical story. From a bone marrow point of view, you get macrocytosis, anemia, thrombocytopenia, coagulopathy when they get liver disease. And in the bone marrow, what you see is replacement of the bone marrow with adipose tissue and decreased bone formation. And there's a whole lot of biology that's underneath all of this. And more recently, people have started talking about, although this is more controversial, whether alcohol can directly impact the kidney. And there's more people with chronic kidney disease who consume alcohol. But whether this is secondary to all the other organs that are affected, if you're not perfusing the kidneys because your heart is not pumping, or whether you've got liver disease. So I think it needs more investigation here. So the summary and takeaways for the talk is that chronic alcohol consumption has many deleterious health effects. Many end organs are affected, from liver, cardiovascular, neurologic, pancreas, bone marrow. Alcohol is a major cause of cancer. And the clinical implications are, perform a good clinical assessment, counseling, check CBC plus platelets to get your FIP4, run a comprehensive metabolic panel one time. In those particularly with cardiometabolic risk factors of family history, manage blood pressure, focus on reducing heavy and moderate drinking, engage in cancer surveillance and education. Thank you. Thanks, Arun. If there's a question, you might wanna answer it. Oh, right. Yeah. Sorry. Catherine, a question? Thanks for the update. I needed the update. Oh, my pleasure. It was... I started out in internal medicine. Uh-huh. I've been a shrink yet for about 20 years now. Okay. Thank you. Thanks. Other questions? Okay. All right. Thanks. All right. Oh, I do have one question. Sure. Which is, do you ever get to end-stage liver disease via diabetics they have hepatitis? Yes, absolutely. In fact, I could talk all day about it. Is there a way to tell me? That's my... Yeah, that's what I do all my work on. That's with 90% of my research portfolio. It is actually an incredibly important cause of liver disease and end-stage liver disease. It's an end-stage liver disease. And unlike, it's even less symptomatic than alcohol until it gets to be very advanced. And it is now... The two are the one and two cause of why we do liver transplants. So the FIB4 came from the diabetic and the non-alcoholic space into what I discussed. So getting a FIB4, if you have a diabetic patient, if you... All your patients, especially if they're obese and diabetic, that means three out of four patients, you know, is a good idea. Doing it one time and just charting. If it's more than 1.3, have them see somebody for further assessment. If it's less than 1.3, you can keep carrying on. Okay, thank you. Okay, our next speaker is Anne Fernandez from University of Michigan. And she'll speak on integrated care for AUD and liver disease. Okay, hi everyone. Thanks. Thank you. For those of you who came, it's wonderful to be here and give a talk to you and to other speakers. So I'm Anne Fernandez. I am a clinical psychologist and an associate professor in the Department of Psychiatry at the University of Michigan. And I have no conflicts of interest to declare. I do have funding from NIAAA and Michigan Department of Health and Human Services. So today I'm gonna talk about integrated care for alcohol use disorder and alcohol-related liver disease, touching on barriers to care for alcohol use disorder, the need for integrated care to treat these co-occurring disorders, in addition to the mental health issues and psychiatric issues that often co-occur with these two disorders. And then present some information about an integrated or multidisciplinary clinic at the University of Michigan that we developed and present some of the data that we've collected from our patients and talk about some of the lessons learned. So in terms of treatment engagement for patients with ALD, there are really two main ways to stop the progression of liver disease. It's a little bit of an oversimplification, but if your etiology of liver disease is from alcohol use, the absolute most important and sole thing that you need to do is to stop drinking. Unlike hepatitis C where we have medications, we don't have medications that can help stop progression of liver disease from alcohol use. The other way to get there is a liver transplant, but you typically need to stop drinking for a period of time in order to qualify for a liver transplant. So there's really one main pathway that's really important to get everybody set on as early as possible, which with some of the important early indicators that we just learned about. So the issue is that the vast majority of people with alcohol-related liver disease do not ever get formal alcohol use disorder treatment. And the numbers are pretty staggering. Alcohol use disorder is in the population around 10%, and surprisingly in alcohol-related liver disease patients, it's about the same. So my colleague, Dr. Mellinger and I, who's part of the Integrated Care Clinic, we analyzed national claims data and found only 10% of patients with ALD got AUD care within a year. We included mental health appointments for that because sometimes those two, they have similar billing codes and only 0.8% got an FDA-approved relapse prevention medication. So everybody there who's orange would be someone with ALD who did not get any alcohol use disorder treatment after getting their diagnosis. And if this were to happen for many other types of diseases, it would just be unimaginable. Like if 90% of cancer patients weren't getting cancer treatment, there would be huge movements to address that. And so I think similarly, we need to think about alcohol use on that scale. This is the way to save people's lives and this is what's killing people. So what do we do? Well, first we have to identify why. And I don't know all the answers to how we address this, but we have to start to think about what are the barriers to care? And there are really two main types of barriers at different levels. The first one is structural barriers. So we have a very disjointed addiction treatment care system in this country. It's often separated from other types of mental health care and other types of general health, physical health care. So it introduces financial burden and insurance difficulties for people. There's transportation difficulties to get to appointments, lack of access, which is actually helped greatly by telehealth now, but still there's a lot of access. There's not enough providers. There's not enough training and lack of culturally tailored treatment. Sometimes women specific inpatient treatment, women sometimes with trauma histories have addiction. They don't want to go into a lot of treatment programs with men, for example, as well as Native American, American Indian and other culturally tailored programs that we need more of. And when we've looked at some of these barriers in more depth, you can see here, these financial and structural barriers are cited in this case by 14%, 7% of people. They didn't know where to go. They couldn't afford it, et cetera. But what about other barriers? So there's another really big area of barriers for alcohol use disorder and substance use disorder care that we don't see in cancer, which is alcohol use disorder is a disorder that doesn't see itself in the mirror the way cancer, let's say, sees itself in the mirror. And that's probably because alcohol is also a neurological, cognitive and learning disorder as well as something in the body. So it impacts how we think, how we remember and how we see things. So sometimes we use the word denial, but I think it's just part of the physiology of the disorder. So one big thing that we find when we look at the national data sets, like the National Survey of Drug Use and Health, Epidemiological Study of Alcohol in these national surveys, the number one reason people don't get treatment is they feel they don't need it. But what does that really mean? What is it that they don't need? Is it that the treatment's not helpful? So what we find is that people have stigma, they're embarrassed. People think the problem might get better by itself, that they should be strong enough to handle it on their own, didn't think this problem was serious enough, and people stopped drinking on their own. So clearly people sometimes think they don't need it as well as think that treatment's not effective. So we have a serious perception problem. And when we've looked at barriers that are in patients with ALD, many of them are similar to those you see with AUD barriers in general, but we also see people with ALD have some unique barriers such that not believing that the alcohol use disorder's there despite the diagnosis. Also early when someone reaches the point where they're getting that diagnosis of liver disease, they often are very sick. So people don't always get that FIB4 early enough. They suddenly have cirrhosis or hepatitis. They're yellow, they're in the hospital. So they're preoccupied at that time with the medical and physical illness, and they don't see the alcohol use disorder as important. But it is. So this is another barrier. And then sometimes overconfidence, particularly early on in sobriety, this feeling like how could I ever go back to drinking after I've just been through that? But many people do. So there's a lot to kind of unpack when you're working with a patient who's just had this disorder. What do you do? How do you address all of these barriers? Some other specific misconceptions about treatment that people have reported in studies are that it's too late, given progression of liver disease. If I stop drinking, it doesn't matter. People haven't considered the broader treatment impact on their mental and emotional health. So one cell that we have in clinics sometimes for people who just can't accept that they could possibly relapse is we'll say, well, this can also help with anxiety. We can help address how you used alcohol to cope with X, Y, and Z. We can give you other tools. So we sometimes have to find other kind of hooks to get people to engage in care. Treatment is also really not something people understand very well, the different types of psychological treatment that's available. It's seen as a homogenous kind of monolith. Usually, I'm gonna go to rehab for six months or I'm going to go to AA, and there's a lot in between. And people often aren't aware that individual treatment is something that's an option, but they think more of peer support groups. So people also tend to underestimate their personal risk of relapse. So even with education, this is a chronic relapsing condition. People will recognize that. I can see that's true for someone else, but for me, that's not gonna happen. And I talk to folks sometimes about the motivational canon of an ALD diagnosis, that you're a cannonball so high in the sky, you've literally just vomited blood. I mean, this is what happens often before someone's in the hospital. They cannot imagine. But I talk to them about how the cannonball eventually starts to fall out of the sky. And so it's very hard to forecast how you might feel in the future and that there's sort of this underestimation or understanding of that because it's hard to predict our own feelings and behavior as humans, not just with alcohol, with anything, with whether I'm gonna eat cookies later after this talk, for example. You just don't always know. You have good intentions, but sometimes things go awry. So the main takeaways are that we really need to address structural barriers to AUD care in patients who have liver disease, as well as the attitudes and misconceptions, which sometimes are just as powerful as the structural barriers and sometimes overestimated and difficult to address in their own way. So that brings me to integrated care for AUD and ALD. So I went on the American Psychiatric Association website because that felt like the right place to pull the definition from for this talk. And they define integrated care as any attempt to fully or partially blend behavioral health services with general and or specialty medical services. And the idea being that if we treat people's mental and physical needs together, we'll better meet the triple aim of improved patient outcomes and satisfaction at a lower cost by addressing common, disabling and costly behavioral health problems. So I'm sure in there you can easily see alcohol use disorder, behavior, debilitating, very costly, and ALD, which has both the alcohol component and the liver disease, that we should be doing these things and addressing them together. So at University of Michigan, myself along with Dr. Mellinger, our hepatologist and Dr. Winder, our psychiatrist, started an integrated care clinic or multidisciplinary clinic, which provides co-located treatment for ALD and AUD. We have a hepatologist, I'm the psychologist, the psychiatrist, and a social worker, and a nurse. And we have MAs that staff our clinic as well. And we see patients, they actually get three evaluations in one day, so it's a lengthy visit. We give them snacks, even, to keep them awake. And so they'll see myself, the psychiatrist, and the hepatologist all in one day. And we will discuss the patients and put together treatment plans together, but also in our own disciplines. But it creates a really amazing cross-fostering of discussion and information so that we can make very specific and tailored treatment plans and address the patient's needs on many levels. So everyone who comes to our clinic has to meet three criteria, have an advanced form of alcohol-related liver disease, so either cirrhosis or hepatitis or both, have used alcohol, drank alcohol in the past six months, and be willing to talk to mental health providers. They don't have to commit to engaging in any care, they need to be informed, and they're not always informed sometimes, or remember, you will be speaking to mental health professionals 90% of the time they know, but the other 10%, they're like, why are you here? And then we have to explain it. Most of them still stick around. So we do this every other week for a half day with four new patient visits at each clinic. And we're going to once a week, actually, in July. So the benefit of integrated care and the motivation for creating this clinic, just like now clinics like this are, and have been in some other areas of liver disease for some time, but more alcohol-related liver disease clinics are happening in the nation over time, and the goal and the reason and motivation for that is because they address both structural and attitudinal barriers. So structurally, when we are bringing the care to patients under one roof, it's going to save them time, it's going to save them transportation, and it's going to make it easier. We accept all different insurances, and we don't have any problem billing for multiple providers on the same day. That's never been an issue. We leverage telehealth as needed, and we make alcohol use disorder screening and treatment universal for all the patients, which reduces stigma. We have all of our clinicians, even the nurse and hepatologist, trained in motivational interviewing, so we meet people where they're at, we're trying to bring treatment to them, and understanding that sometimes they may not want that. So we have to be artful in how we do that at times. And I think one of the really big single things that this does is it leverages patients' motivation. People want to see their hepatologist. We don't have a problem having people come in to get the physical healthcare. It's the mental healthcare that's not always as appealing or desired, so we yoke those two things together, and we make it so that you see everybody on the same day. And that really gets people through the door. And we address treatment misconceptions when people come in, and we do things like we have those conversations. If some people want alcohol use disorder treatment, when they've met us, they see the psychiatrist, they see me, they understand who we are, we explain what we do, that immediately reduces a lot of barriers. And then they're much more likely to come back and see us again after having gone through that. We also sometimes start by addressing insomnia. Like we'll say, okay, well, you don't want to talk about alcohol, that's fine. You have a trauma history, you have anxiety. I am trained in cognitive behavioral therapy, in DBT, in all different things that we can use to address different problems you have. And then alcohol use disorder, we can weave in, or we address underlying issues, and then alcohol use disorder may improve from that. So some outcomes and data from our clinic, so these are just observational data. We're, it's not randomized, but we have collected data from chart abstraction from our patients, and we've, as of the fall, we've seen 156 patients with ALD, about half women, predominantly white, and 2.5% Hispanic. Michigan has a low Hispanic population, even for the nation. The mean age is 44, and 44% have Medicaid, so high proportion of public insurance. And in terms of diagnoses, everyone who's ever come in has received an alcohol use disorder diagnosis following a thorough evaluation by trained clinicians, severe alcohol use disorder in 86% of cases, and moderate in about 13-14%. 78% also have another substance use disorder, and over 80% have a mental health comorbidity. So to stress the importance of mental health care providers in a hepatology setting, when you consider that complexity of patient diagnoses, that creates the need for a lot of expertise that's often not there when someone comes in to see a hepatologist for the first time. Also, about one in four have a trauma history as well, so there can be a lot of complications. And in terms of treatment at our clinic, we're still pulling some of the chart data to get some outcomes from this, but I can say 100% of people have received at least one visit of a psychologist or social worker, and one from the psychiatrist. So a hundred percent of people have received alcohol use disorder care in terms of the metric that we used for that previous study that I showed, and 64% received a medication for alcohol use disorder after enrollment in the clinic. So if you think of how many more people that is, it's tenfold higher just for any treatment, so you can really reach a lot more people in this way. And the medications prescribed, so I'm the psychologist, not the psychiatrist, but I'm at the Psychiatry Association, so I made sure to highlight. We do a lot of gabapentin prescribing for off-label AUD. It also helps with anxiety. And insomnia, so it's actually a very good medication that Dr. Winder prescribes frequently. And we do prescribe naltrexone, which obviously at certain levels of liver disease severity can be unsafe, but in many cases is safe, and the psychiatrists and hepatologists talk about this for more advanced patients, whether that is a good idea, which is another benefit of the clinic. So we have 21% of naltrexone prescriptions, and then the campers as well. So treatment preferences, I'm noticing the time, so I might zip through some of these, but there, so we have 63% of people prefer, they ask for one-on-one therapy when they come into the clinic. But before the clinic, only 20%, that was the type of treatment they had in the past. 51% have had AA in the past, but only 10% are asking for that or wanting that when they come to the clinic. And then about 31% said they didn't want any, didn't want any treatment before coming into the clinic, but only three, or is it eight, eight percent do not want any treatment when they come in. So we looked at outcomes pre and post, six months pre and six months post clinic evaluation, and as you can see, there is a very large reduction in hospital utilization, admissions, and ED visits, six months pre to six months post visit, which again, this is observational data, so you can only infer so much, but it at least is moving in the right direction. So just a brief recommendation for clinicians generally is, you know, whether you can start an integrated care clinic at your site or not, bringing treatment to the patient really addresses structural barriers, assessing readiness, past treatment experience, and preferences can really help in understanding what types of treatment a person might want to need, and then offering a menu of treatment options, and that might even include books, apps, there's some pretty good, University of Michigan Addiction Center has some actually pretty good resources, if you, if you google it, where we have a lot of apps, we have a lot of books, we have a lot of chat groups, online resources for this large segment of people who say, I don't want treatment. We can at least give them things to help support and self-support change, which people can achieve. It becomes more difficult with more severe AUD, but it's not impossible by any means. So just in brief, I might skip this, so prescribing to patients with ALD, many AUD medications and psych medications are safe for patients with liver disease, so consulting with hepatologists or for other doctors if you want to prescribe those medications is recommended, and just knowing about hepatotoxicity of certain meds versus those that don't have it is important, and then psychiatry may be the first point of contact sometimes that someone may have, so if you suspect that a person has or could develop liver disease, it's a good idea to refer them to their PCP for evaluation and and see if that could be happening, because it often happens suddenly to people when they don't realize what's been going on under the surface. So really brief conclusions. Why integrated care? Considering that stopping alcohol use is the only way to stop the progression of ALD outside of transplants, so treating AUD should really be at the center of ALD care, and if you build it, they will come. We have all these treatments and medications that work, and so what we really need to do is get clinics reduce barriers to care, not create more for patients with addiction who are often stigmatized, like you have to want it. We should make this the easiest care for this population. We have to reach out to this population. It's the total opposite of the traditional model of how we think about addiction, and so we can do this by bringing addiction to patients, so. Thank you to NIAAA and the organizers today. My colleagues Jessica Mellinger, Scott Winder, Kristen Clevering, and Amanda, and thank you. Now I can take some questions after. Thank you. This is absolutely, I mean, it's a completely different attitude. I've seen so much pejorative folks with alcoholism coming to care, so like society as a kid, where they live and die, you know? Yeah, yeah, no, it's really staggering, and it it's society, and it even pervades clinicians' views, and even historical addiction care views is actually some of the strongest barriers, believe it or not. People in the field, sometimes some of the 12-step ideas, there are inpatient programs that take people off suboxone because they don't believe that medications for OUD are, you're not sober if you're using them, so I think there's movement, but it's a difficult path and something that takes education for doctors when they're in med school, for psychologists even, and for society generally, so it's something where we take very seriously at our clinic to try to destigmatize and make a more welcoming environment, and we think that that's part of why we get more people engaged, but it's still really hard, even with that. Are there a lot of other places around the United States these days doing this sort of thing? Yeah, yeah. Well, I think specifically for an integrated alcohol-related liver disease clinic, University of Michigan, my understanding is we were the first to do it, but there's one in Wisconsin now, I think Mayo Clinic, and I know you, yes, you guys have been doing it for a long time with NASH, and now, and integrating alcohol into that, so maybe you guys were even doing the alcohol piece first. Okay. Yeah, yes, and overlap, yeah. Yeah, that was gonna be my question, because we're talking about obesity and alcohol at the same time, so do you also bring in like dietary interventions to go along with it? It's like you said, insomnia might be an entry point, but would also kind of diet be one or not? Yeah, that's a good question. Yeah. Yeah. Right, exactly. Yeah, yeah, yeah, and I think a lot of our patients do have both. The, we haven't brought that in as much, and actually it was interesting talking to you about about the model of care you've developed doing both, because it kind of capitalizes on a lot of resources. We sort of have it separate a bit at Michigan, although it's really not separate at the patient level, which, you know, so it makes it a little bit artificial, and some people do, they don't have NASH, they have the malnutrition more than anything that they're, you know, using alcohol as a, as their nutrition source, so it kind of depends, but yeah, I think that's a good area for future growth too. And then I have another question. So, do you find different success, I guess, between kind of chronic ALD versus people recovering from bouts of AH? Because you would probably see them after the bout was, after they'd recovered. Yeah, they'd come to your clinic, is that how it works? Yes, so we have people, exactly, so we'll often get people after, for AH, you know, it like had sudden onset and they nearly die and then they end up at our clinic versus folks with cirrhosis, where sometimes that's been going on for longer, and then there's also people who have both acute and chronic, so there are some differences in some ways, although I find most people, even with hepatitis, usually have a very long chronic alcohol use history prior to that happening, so I wouldn't say it's hugely different in terms of like the AUD focus, but it would be interesting to probably like dig into our data a little more. Yeah, but I, yeah, because of the AUD typically, like they've reached severe AUD by then, so I find the treatment is, is pretty similar. Yeah. So, you know, it just seems from our own experience, that there are people who consume, indeed, whiskey drinking, but it's more social. Yeah. Then you go to a phase where you're actually dependent. And then you have the pulmonary heart disease. Yeah. And according to the literature, people talk about these three phases. But do you use differential approaches, or are there, as a clinician, who comes from an end-organism setting? Yeah. How should we think differently about where people are in this case? Yeah, there's some, I don't have the figures, but there's some great figures that show, like, you know, people, traditionally, we had alcoholism, and we had not alcoholism, and it was just two camps, they were black and white, and never the two shall overlap, which is completely artificial as well. So, I mean, now we can see there's a spectrum of alcohol use disorder that can run from mild to severe, but then also that sort of risky drinking, where it might not even quite reach alcohol use disorder status. And there are really different approaches you would take. In this clinic, we, of course, everyone had either moderate or severe, so we are hitting them with a pretty high dose of more intense, higher level of care. But when you get to those lower levels of care, kind of like the FYB4 score, is you're like, well, you know, you might be someone who could manage this on your own more easily. Here are resources that you can use. You do those brief interventions, like you were speaking to me about earlier. So giving people more like a one-time intervention, maybe have a follow-up, see how they're doing, give them some apps to track their drinking. For someone who's in a more risky or mild alcohol use phase, that might be enough. Once someone, of course, has severe AD, the addiction and the dependence is very intense, that becomes much more difficult to, quote-unquote, control, because you're essentially keeping yourself alive by drinking at that point. So, yeah, definitely different levels and intensity. There's something called the ASAM continuum that matches the type of addiction care across five dimensions of severity of addiction that also can help for mapping the type of approach to the intensity, too. Excellent. Thank you. Yeah, thank you. And the third speaker today is Mandana Khalili. She's from UCSF here in San Francisco. And the title is Telehealth Approaches to Vulnerable Communities. Thank you, Dr. Nagy. Let me see if I can get... Oh, maybe right there is fine. There you go. Thank you. Perfect. Excellent. Okay. Well, thank you very much for that kind introduction, Dr. Nagy, and thank you so much for attending this talk. I have the challenge of wrapping things up with focusing on the vulnerable populations, which is essentially disproportionately affected by alcohol use disorder as well as alcohol-associated liver disease. Let's see if I can push this forward. There we go. These are my disclosures. Okay. So we know that the prevalence of unhealthy alcohol use is greater in the young adult population as seen in this figure. Younger age, female sex, and Hispanic ethnicity are also disproportionately influenced by alcohol-associated liver disease burden and liver failure in this country. Since the pandemic, there's been a highest relative increase in the rate of alcohol use disorder in women and black individuals. And with that, there has also been an increase in alcoholic hepatitis rates of hospitalization among these groups. As well, there's been a relatively high or increased rates of alcohol-associated liver disease mortality in women and young adults. And as we all know, vulnerable populations are disproportionately affected by these adverse outcomes. When we think about minority health or health of the vulnerable populations, as shown in this figure, it is important to understand that the factors that influence the health of individuals is complex and is multifaceted. And with that, it results in disparities in alcohol-associated liver disease. These factors can span biological, behavioral, physical built environments, sociocultural, and health system factors. And within each of these, there are levels of influence that involves individual factors, for example, social determinants of health or feeling stressed and alcohol treatment preferences. Interpersonal factors, as was outlined earlier, for example, stigma or social support. Community factors, such as presence and availability of safety net services, as well as societal factors, as expressed earlier. For example, accessibility, availability of organ transplantation, as well as strict Medicaid policies. With the onset of the pandemic, recognizing the anticipated rise in the unhealthy alcohol use and consequently the adverse outcomes that we see with regards to liver disease, the liver community mobilized and made the following recommendations. Use telehealth and secure messaging services to provide alcohol use counseling and provide hepatology specialty care services, termed telehepatology. Use telepsychiatry to address both substance use problems as well as addiction issues. And mitigate the effect of social isolation in order to reduce use of alcohol in frequent check-ins with patients, emphasizing also abstinence, as well as encouraging patients to reduce alcohol consumption. In the liver disease setting, we know that using telehealth has shown to be very effective in achieving cure in hepatitis C. This has been going on now for several years, and more recently it's resulted in increasing access to liver specialty care in patients with more advanced liver disease or those with cirrhosis. It's also recently been shown that it's effective in improving implementation of lifestyle modifications such as weight loss in the setting of fatty liver disease, and also monitoring of patients following receipt of liver transplantation. As was expressed earlier, use of telehealth can also increase access to addiction services. With regards to alcohol use, it's been shown to reduce alcohol consumption, improve accessibility, quality of life, reduce treatment costs, and increase implementation of coping skill, as well as motivation for change. So consequently, it is no surprise that telehealth approaches are now being considered for co-managing patients with alcohol-associated liver disease, and this is now emerged as an important opportunity or innovative opportunity for care delivery that's currently being under investigation. In the hepatology setting, as you can imagine, telehealth approaches can increase treatment access and it can increase or induce abstinence and prevent relapse, and with respect to liver disease, it can provide patients with education in addition to treatment access and consequently prevent progression of liver disease. Studies have also shown that the integrated alcohol-associated liver disease and AUD treatment improves patient outcomes. We know that treating AUD with medication significantly reduces the incidence of alcohol-associated liver disease, and it also, as it is shown in this figure, reduces progression of liver disease to liver decompensation, even if the treatment for alcohol use disorder is initiated after the cirrhosis has been diagnosed. There are many advantages of telehealth as a model of care delivery. As you can imagine, it is easy to use, low cost, its potential to decrease wait times, missed visits. It's been shown to be very effective in outcome management in chronic conditions, improve communication with the providers, and enhance medication adherence. But relying on digital technologies can also lead to widening the disparities that we see in patients with alcohol-associated liver disease and alcohol use disorders, because relying on technology is really separating those individuals who have access, infrastructure support, and skills to use them from individuals who don't. So digital literacy, access to internet connectivity, language compatibility, all of these have been actually now recognized as social determinants of health that are interrelated with other determinants such as housing, transportation, income, education, etc. So awareness of these issues and addressing these factors are definitely important in achieving health equity in vulnerable populations. So when we think about considering improved telehealth use in the vulnerable population, those who are socioeconomically disadvantaged or medically disadvantaged, those with a high proportion of minority groups, it is important to really center this on equity. What I mean by that is recognize that these patients have disproportionate access to care in general to begin with. There may be a low health literacy issue. There are cultural responses and cultural perceptions that may be different. There may also be gender-based perceptions, for example, that could be different. There is an issue that could exist with regards to trust in the mode of care delivery, and they may need targeted support with telehealth implementation. There should be flexibility in implementing telehealth options such as availability of telephone versus video visits, even though suboptimal, and also ensure that there is language capacity. And in thinking about those things, always remember that there's also this intersection of these factors with other spheres of exclusion that exist among these populations, such as age, sex, race, and other social determinants of health. But what happened when the pandemic occurred? Well, interestingly, now the populations who previously did not have access to this technology, it became accessible to them. As seen in this figure, in a study that was conducted in 16 states using EMR data, looking at before and after the pandemic, it showed that the use of telehealth among the safety net clinic increased from 27% in rural isolated areas to 52% in urban areas, a significant increase. But as you can also see, that rural patients had lower odds of telehealth use compared to urban setting, especially with the isolated rural settings being the least. This suggests that there needs to be improvement of access to and use of telehealth care among rural patients still, and so that should be certainly considered. Data from early in the pandemic period also showed some inequities in accessing telehealth. In a retrospective medical record review for a couple of months after the pandemic, over 148,000 patients that scheduled telehealth visits in either primary care or specialty care were reviewed. They showed that older age, Asian patients, non-English speaking patients, and those on Medicaid had lower rates of telehealth use, while older females, Black and Latinx patients, as well as those who had low income, had suboptimal use of telehealth with reduction in use of video over telephone use. In another study where they looked at individuals who particularly met the low income or poverty level threshold federally, Hispanics and Asian patients are more likely to use telehealth than non-Hispanic Whites or Black. Patients who were employed full-time or they were female or younger individuals or those who had completed a bachelor's degree were more likely to use telehealth and the income appeared to positively be associated with telehealth usage, so there was some correlation there. What about telehepatology? Well, the data on this is less robust and we've seen that in a retrospective cohort study that was done in all adults patients seeking help at the hepatology clinics at Duke University Health System, comparing telehealth visit a couple of months before to a couple of months after the pandemic, that there were some disparities in overall use and also suboptimal use of telehealth in these populations, especially among vulnerable populations. Those who were older, Black, and also had Medicare, Medicaid tended to use the visits less and also have a suboptimal use of this modality. Well, most importantly, what are the patient report experiences with telehepatology? The data here is also very limited. In a study of feasibility, outcome, and safety of telehepatology for a couple of months after the pandemic among 210 randomly selected patients, patients' convenience rate, satisfaction, improvement rates were significantly high and there was also an improvement in physical and mental quality of life in these individuals after their index telehealth encounter. The dissatisfied patients were more likely to have lower diagnostic rates, they were unsuitable for teleconsultation, for example, may have had a decompensation of liver disease, non-compliant, had poor understanding, and uncomfortable conversations during teleconsultation. These are all features that may be more prevalent among vulnerable populations. Similarly, we conducted a prospective study of 111 patients receiving care for alcohol and non-alcohol associated fatty liver disease from June of 2020 to May of 2021 in the San Francisco Safety Net Healthcare System hepatology clinics. About a third of these patients were male, two-thirds were Hispanic, 21% were Asian, and 85% had annual household incomes of $30,000 or less. And we found that decreased physical activity and heavy alcohol use were the most influential on self-reported weight gain in this population, as it was expressed by both of our speakers previously, and that the primary modality of care in these individuals being weight loss was significantly compromised. Importantly, we noted that Hispanic ethnicity was significantly associated with lower satisfaction with telehepatology, suggesting that there may be a potential cultural influence or perceptions about this modality of care delivery. In a follow-up study to late pandemic, now March of 2022, we further explored satisfaction in telehealth while accounting for time since the pandemic onset in 220 patients within the same safety net system. Once again, majority were women, 60% or more were Hispanic. While most of our patients were actually very satisfied, about 70% reported being somewhat and very satisfied with telehepatology visits, Hispanic ethnicity remained independently associated with lower telehepatology satisfaction, even after inclusion of other social determinants of health measures. Interestingly, there was a recent article that was published that had a qualitative study done in the same health care system, speaking with 25 semi-structured interviews with patients who were multilingual and participated in both primary care and specialty clinic. Participants were diverse with respect to age, language, and race ethnicity, and use of smartphone, and this study showed that high satisfaction with telehealth can coexist with patient express hesitation surrounding the perceived efficacy and also self-efficacy and digital access barriers. While most of the patients were actually indicating that they felt that the visits fulfilled their medical needs, were convenient, and they were satisfied in general with telehealth care, they also felt that they still preferred in-person visits, and those concerns were surrounding the telehealth visit relying on patients' ability to access telehealth, but also as well as monitoring and managing their own health without having a physical examination. So perhaps some of these factors were actually playing a role in what we are observing in our more ethnic patient populations. We're currently exploring alcohol use and telehepatology care for vulnerable cirrhosis patients in our population after the pandemic. Our bigger study has various components, including evaluation of care delivery and impact of COVID and post-COVID on cirrhosis care, as well as implementation of a randomized clinical trial of step care intervention in alcohol management within the hepatology setting, but I'm going to talk to you today a little bit about the telehepatology use and experiences and capacity in this population. This study was based on the premise that patients with cirrhosis were acutely vulnerable to COVID-19 pandemic-related disruption and that alcohol may really complicate telehepatology care delivery in this setting. We evaluated the relationship with alcohol-related problems and telehepatology capacity, use, and satisfaction among patients with cirrhosis at three health care systems, two VA and one urban safety net health care system here at San Francisco. 225 randomly selected patients completed surveys that included alcohol use disorder identification tests or audit, telemedicine satisfaction and usefulness questionnaire or TSUQ, digital capacity questionnaire, and social demographic information, and we performed generalized linear models with accounting for various confounders in order to evaluate the relationship between alcohol problems and telehepatology satisfaction. Participant characteristics are summarized here. Majority were older. The mean age was 63. Most were male. Majority were either white or Latino, 40% each, and a quarter of the patients spoke other languages than English and had less than high school education. Nearly 70% were born in the U.S., but most, 60%, had low income of less than or equal to $30,000, and 21% had paid employment. The predominant etiology of liver disease in this population was alcohol-related, and about a third of these patients had decompensation of cirrhosis. A hundred percent, importantly, endorsed having access to digital devices like phone, tablets, or computer. Eighty-eight percent had smartphone. Nearly a hundred percent could use their devices in private places, and also they indicated that they used their devices for more than four out of eight tasks on a daily basis. Seventy-five percent of the cohort had used telehepatology with a mean telehealth use satisfaction score of 3.7 out of 5, and satisfaction with telehealth visit itself at 3.8 out of 5, so pretty high satisfaction. When evaluating alcohol use in the prior 12 months, about a third of the patients, now these are end-stage liver disease or cirrhotic patients, endorsed alcohol use. The mean audit score was 3.9. Nineteen percent endorsed risky or hazardous use. Seven percent harmful. Eighteen percent high-risk alcohol use or alcohol dependence. Seventeen percent of the cohort had said that they had had a change in alcohol use during the pandemic, and 43 percent actually indicated participating in a substance use therapy during their lifetime. We found that on multivariable analysis, alcohol-associated liver disease was associated with lower hepatology use, higher audit score, suggesting also alcohol symptoms were associated with lower satisfaction. Higher pandemic stress was associated with greater telehepatology use, as it makes sense, as well as better quality of life and Latino ethnicity. Older age was associated with lower satisfaction with telehealth system. In this vulnerable population, we found that the patients with cirrhosis had capacity to participate in liver care during the COVID-19 pandemic using telehealth, but 25 percent did not participate. We found that higher alcohol-related symptoms and alcohol-associated liver disease was associated with lower participation in telehepatology and satisfaction with it, as compared to other causes of liver disease. Vulnerable patients with alcohol-related problem and alcohol-associated liver disease, especially those who are older or have poor quality of life, therefore may require tailoring of telehepatology care delivery in order to appropriately deliver their liver and alcohol use disorder care. Whether these reported experiences that we found influence alcohol treatment delivery using telehealth in this population is currently being studied. So, in summary, I wanted to emphasize that vulnerable patients are at risk of experiencing disparities and alcohol-associated liver disease incidents and outcomes. It is important to note that telehealth approaches for vulnerable patients with alcohol- associated liver disease may benefit from integration of alcohol treatment and liver management services to enhance satisfaction, but may also require some tailoring to achieve health equity in this population. In closing, I wanted to acknowledge my collaborators, mentees, research staff, and our patients, and of course NIAAA for supporting the work that I just presented. Thank you. I have a question. So, is the disparity between satisfaction like Hispanic versus not, is that telehealth, is that the same with in-person visits or does that, is it different? That's a very good point. Yeah, you're bringing, we didn't specifically do that type of an evaluation or assessment, but as I shared with you, when they were looking at a qualitative study that was done in patients, most majority of them actually Latino and Spanish-speaking, they identified that the feeling or the impression was that in delivering care, the touching of the patient, being there and having physical examination, then not relying on the patient for their particularly symptoms and management was more satisfying. So, I would only assume that there's those cultural influences. Questions? Yes. We have not. That's a good point. That's wonderful. Now, we do have, so we have these scores presented as a whole for services on a regular basis. Now, we don't have incentives or anything like that. But, yeah. And it may be that some clinicians are better at telehepatology than others. Yes, the provider ability should play a role. But, I want to remind us, though, that this, again, overall, the satisfaction was quite high. I mean, I'm not a hundred percent sure what we would have seen in person. Maybe it would have been even lower than what we saw, which was 70%. But, definitely, there is an art of medicine that occurs, whether it be in person or over telehealth, for sure. Excellent. Thank you very much. And thank the two of you for attending. We're so glad you were here.

alcohol-associated organ damage

psychiatric care integration

end organ impacts

oxidative stress

public health concern

integrated care model

structural barriers

multidisciplinary approach

telehealth access

digital literacy

equity-centered telehealth