Welcome to the 2021 Hepatology Associates course, titled The Dance of the Serotic Patient, Multidisciplinary Team Approach. My name is Dawn Harrison. I'm a family nurse practitioner at the University of North Carolina, Division of Gastroenterology and Hepatology. It is my extreme pleasure and privilege to greet each of you this morning, and thank you for attending this year's meeting. I would like to say a very special thank you to all the faculty members for their participation in providing a sensational 2021 program. Before I proceed any further, I want to express my deep appreciation to Suzanne Robertas for her dedication and wisdom in co-organizing and co-moderating this year's program. The learning objectives for this program are, describe the multidisciplinary approach to evaluation of a patient with end-stage liver disease, review practice guidelines for the patient with end-stage liver disease, and apply appropriate goals. Evaluate options when liver transplantation is not a viable option for patients with end-stage liver disease. In an engaging format, our program experts will fulfill these objectives and much more. Now, without further ado, I would like to introduce each expert and the title of his or her session. Dr. Gerald Widener is a psychiatrist with the University of Michigan. The title of his presentation is integrating care for patient with chronic liver disease, mental health, and substance abuse disorders. Amanda Von Jacobs is a solid organ transplant dietitian with Rush University. She will be discussing nutrition in patients with cirrhosis. Annalise Nolan is a pharmacist at Ohio State University. She will be sharing the topic, what you put in your mouth, your liver sees. Karen Stringer is a physician assistant with MedStar, Georgetown University Hospital. The title of her talk is acute on chronic liver failure. Corey Beck is a nurse practitioner with Loma Linda University Health. Corey's presentation will be focusing on the topic of post-liver transplant care for the community provider. Lee Turner, nurse practitioner, and Chelsea Samens, pharmacist, are both affiliated with Penn University Medicine. Together, they will be addressing the topic, optimistic infections in end-stage liver disease. Dr. Victor Navarro, hepatologist at Albert Einstein Medical Center, is presenting the topic, end-stage liver disease at the end of life. Our final session presenters are Dr. Ashurag Desai, transplant surgeon with the University of North Carolina, and our much-honored speaker, Mr. Larry Cockrell, liver transplant patient. The title of their session is called My Story. Mr. Cockrell and Dr. Desai will rhythmically share the dance steps they both performed, allowing Mr. Cockrell to be here with us today. We are elated to bring you an up-close and personal patient account, along with a wealth of applicable professional knowledge today. Therefore, grab a cup of coffee, sit back, get comfortable, and we hope you enjoy today's program. Thank you. Hello, I'm Scott Winder from the University of Michigan. I'll be talking about integrated psychiatric care for patients with chronic liver disease. I have no financial disclosures or conflicts of interest. We'll look at two cases, one from psychiatry and one from hepatology, and define care integration. Then we will explore components, processes, and models of integrated care. These cases are de-identified and data changed to protect privacy. Both patients have previously given permission for their cases to be used for medical education. Jane Doe is a 44-year-old female with depression, anxiety, and a severe alcohol use disorder with known associated fatty liver. She also has a history of acute pancreatitis and gallstones. She's currently taking citalopram and bupropion. She presents to Addiction Psychiatry Clinic for evaluation. Disulfiram is started and baseline LFTs are obtained. One week later, she follows up sober, but with a new rash on her neck and back that might be a sunburn. No labs are drawn. Two weeks later, the rash worsens and spreads. She's still sober and highly engaged in Alcoholics Anonymous. Disulfiram dose is lowered, no labs drawn. One month later, there's an ache in her right upper quadrant with associated weight loss. This was referred by psychiatry to the PCP and no labs were drawn. A week later at the PCP visit, he or she documents additional weight loss, early satiety, anorexia, worsening right upper quadrant and epigastric pain and scleral icterus. Patient is emergently referred to the emergency room. Upon arrival, her urine is dark and LFTs are elevated. The patient stopped Disulfiram three days previously, she tells the clinicians, with a slip back to drinking in the meantime, no other ingestions. During her ensuing eight-day medical admission, mental status was stable and LFTs trended downward and she's discharged from the hospital to close outpatient follow-up. Mental status then abruptly changes four days later, prompting readmission and subsequent concerning lab trends ensue. The patient is listed status 1A and is transplanted about 10 weeks after her first Disulfiram dose. In the years since, her graft has been healthy and transplant psychiatry has treated depression and PTSD symptoms related to her difficult course. She has processed significant anger toward the psychiatry team who prescribed Disulfiram. Now, let's look at a hepatology case. John Doe is a 49-year-old gentleman who underwent liver transplant last year, we'll say, for hepatitis B-related cirrhosis, comorbid seizures and severe anxiety. He had never been evaluated by a psychiatrist. During a transplant hepatology outpatient clinic visit, where his LFTs were elevated and a medical admission was already planned, he was noted to be in acute psychological distress and his hepatologist requested a transplant psychiatry curbside consult. Chart review indicated that the patient had never reported any substance use during past transplant evaluations and encounters. Psychiatric interview quickly indicated that the patient readily met criteria for a heretofore undetected severe alcohol use disorder. Chiatry discovered that the patient had drank mouthwash before his liver transplant, trying to raise his MELD score and accelerate his clinical timetable. He thought the transplant would cure his alcohol use disorder and he had actually started to test out his new liver post-transplant with alcohol when it didn't. His historical seizures were likely alcohol-related. During his ensuing hospital stay, his LFTs trended down and there was no rejection found on biopsy. He was discharged to a residential rehab facility, the first addiction treatment encounter of his life. Two weeks later, while still in rehab, he was medically readmitted for elevated LFTs and a stricture was noted on ERCP and a stent was placed. He was also found to be depressed and making delusional and paranoid statements for which he was admitted to inpatient psychiatry where medications were adjusted for his mood, thinking and alcohol cravings. He did not participate much in unit programming because of his anxiety and he was discharged back to rehab where he ended up only completing 30 of his 90 days because when he left the facility again for a scheduled endoscopy, he declined to return. Two months later, he tried to end his life with a 25-gram ingestion of acetaminophen. After his outside hospital medical admission for acetaminophen toxicity, he was admitted to that hospital psychiatry unit before they requested transfer to the academic medical center where the transplant center is located. The academic hospital psychiatry unit declined readmission due to their large waiting list and the patient's previously low participation on the unit. So transplant surgery admitted the patient with psychiatric consultation, which included daily monitoring and bedside psychotherapy and eventual discharge to local psychiatric follow-up. In the years since, patient has been homeless at times, relapsed severely to alcohol multiple times and has been intermittently non-adherent with psychiatric and transplant care. He is currently living in a halfway house, working full-time, doing well overall, and he is sober. These cases contained many successes of care integration and there are many words we can use to describe the bridges we need in order to integrate care between hepatology and psychiatry. The underlying concepts are the same. We can use whatever words we use. More about these concepts in the books cited above. Without strong bridges, patients fall into dangerous gaps since hepatology and psychiatry are commonly disconnected specialties within the health system, despite the overlapping pathophysiology that we all treat. This means that psychiatric and liver care too often is characterized by low interprofessional collaboration, poor care access and quality, the breadth of ALD pathology, incomplete ownership of the patient, and discontinuous care. You probably detected some of these gaps in the cases that we just discussed. Care integration means that multiple specialties effectively collaborate during episodes of patient care, creating a superior breadth and quality of care. For chronic liver disease patients with mental health substance use and behavioral challenges, this likely entails these specialties. A culinary metaphor can help depict different forms of care integration. Multidisciplinary integration is like a salad whose ingredients can be readily distinguished from one another. Such teams work well together, but they remain well within their training roles. Interdisciplinary teams are similar to dips or soups, where ingredients are much more blended together while still being distinguishable from one another. Medical teams like this exchange substantial training and skill, thus blurring their practice boundaries. Clinicians on transdisciplinary teams cannot be distinguished from one another because the hepatologist is providing brief psychotherapy, for example. These teams are like this cake whose different ingredients cannot be readily discerned at all. Let's look at the components, processes, and models of integrated care. Let's first ask whether psychological treatment within medical populations is even worthwhile. This is a small slice of the literature examining integrated psychological services in various medical populations. In general, I'm sorry, in general medicine, integrated addiction care improved abstinence and mortality rates compared to standard care. In liver transplant, an embedded alcohol addiction unit reduced post-transplant relapse and mortality. In hepatitis C patients, embedded substance use care favorably impacted abstinence rates and addiction severity as measured by a standardized scale. And in alcohol-related liver disease, interprofessional liver psychiatry care reduced patients' MELD scores and hospital utilization rates. There are many reasons a liver team would seek integrated care for a patient. This does not mean that appropriate psychiatric treatment is readily available or that it would solve or improve any of these challenges, but teams could rightfully consider psychiatric treatment for these and other indications. Care integration is important in the liver population where studies show that as many as one in five ALD liver transplant candidates were positive for an alcohol biomarker at their liver transplant evaluation. Another study found that 1.4% of ALD liver recipients had a positive biomarker on the day of their transplant. Table two shows how questionnaires and addiction specialists improve detection accuracy of drinking and sobriety in a post-liver transplant patient, I'm sorry, in a post-liver transplant population beyond a hepatology evaluation alone. Beyond just substance use, table three shows us the elevated odds ratios for many psychiatric and substance use disorders in the ALD population when compared to other chronic disease and hospitalized populations. All of these data clearly signal the need for integrated care. The process of care integration takes different forms and can be catalyzed or blocked by various factors. Another metaphor helps us conceptualize the different ways that integrated liver care can be formed over time. If a tree trunk represents typical hepatology services, an adjacent branch as integrated psychiatric services, then that new branch could naturally grow and form as part of the tree's normal development. An example would be a liver team that has long had a group of psychosocial specialists embedded within it who grow and expand with the liver clinic itself. These clinicians extend the liver clinic services and influence its culture. Or it could be that psychiatric services are grafted onto the trunk in a sudden and more invasive and less natural process. An example would be a liver clinic that's responding to a new institutional initiative or a bad clinical outcome and needs to quickly implement new psychosocial procedures. Any new care integration venture is more likely to be successful when its clinicians have shared goals about patients and clinical operations, shared knowledge about the breadth of people in pathology, mutual respect for all clinical roles and effective professional and personal communication. Stressed clinicians who do not trust or relate well one with another are less likely to be successful. Medical disciplines have their own cultures and norms and human beings are naturally tribal and hierarchical. These can be significant barriers to durable and quality care integration. So what are the components of integrated care? Four areas are worth a closer look. First, the actual processes of coordination and co-location. By this, I mean how a team comes together and works together. This impacts relationships, trust, shifts in culture, interprofessional education, shared skill sets and workflow innovation. Psychotherapy, pharmacology and toxicology are also key elements. Let's briefly talk about each of these to finish the talk. Care integration and coordination can take several forms depending on the resources, priorities and will for change of any particular clinic or health system. These levels increase in degrees of integration and interprofessionalism and range from completely unaffiliated clinicians where liver and site clinicians have little if anything to do with one another to fully co-located and cross-trained clinicians treating the same patients at the same time in the same clinic. Informal affiliation means that liver and site clinicians periodically refer one to another without much other connection. Clinician-to-clinician integration is peer-to-peer education and consultation similar to what Project ECHO accomplished for the dissemination of hepatitis C expertise. Institutional integration means that a health system's own psych and liver resources develop formal affiliation and collaboration. Even the most collaborative liver clinics with co-located psych specialists will still not be able to provide all levels of psychological and behavioral treatment for its patients across all disease stages and phases of care. Ensuring that liver patients have access to a full array of available psychiatric and behavioral treatments will require deliberate collaboration and outreach to multidisciplinary colleagues throughout the health system and surrounding local areas. So what psychotherapies work in liver patients? Few have been tested in liver disease and transplant patients. Psychiatric consultants and colleagues can assist hepatology in prescribing and administering therapy to liver patients when psychological and behavioral problems like those discussed earlier should be addressed as part of a liver treatment plan. We won't have time to discuss each of these, but the citation below gives additional detail. Several medications are available for the treatment of substance use disorders which are commonly encountered in liver patients. Each has different considerations for use in end-stage disease and in transplant. There are few studies to guide their use in the liver population. Multidisciplinary decision-making is optimal when using medications given the intricate interplay of pathophysiology, drug interactions, and various types of risks and benefits. Selecting an agent, covering multiple symptoms with the fewest agents, adjusting the dose, and changing or adding medications are best done in integrated fashion. Medicines for other psychiatric conditions are not shown here, but should be approached in the same way. Toxicology is an essential tool which objectively documents substance exposure. Alcohol biomarkers are commonly used in hepatology and are a good example of care integration. Urinary ethylglucuronide and ethylsulfate are ethanol metabolites detectable during a three- to seven-day detection window. Ethylsulfate doesn't have the false positives and negatives that can confound ethylglucuronide, which is the more commonly used assay. Both are highly coordinated and correlated. Serum phosphatidylethanol, or PEF, is a marker of alcohol exposure that persists in the bloodstream for up to a month. It may perform differently quantitatively in different sexes and in different drinking patterns, as shown. Quantitative PEF values correlate with audit scores, meaning the higher the number on the PEF result, the higher likelihood or correlation with moderate to severe drinking problems. An important note, positive toxicology never means that a person has an addiction, and negative tests don't necessarily mean that they haven't used. Expert consensus agrees that toxicology should be accompanied by a thorough and expert clinical interview to make a diagnosis and prescribe a treatment plan. Integrated psychiatric providers can provide this for liver patients. Substance use disorders are the quintessential example of why integrated care in liver disease before and after transplant makes sense. Since substance use disorders affect all stages of liver disease in phases of transplant care, we identified a distinct need to bring integrated psychiatric services to ALD patients upstream from transplant, as well as to transplant candidates who may have been delisted in hopes of getting them back in qualifying shape to be successful in liver transplant. Early outcomes published this year suggest that our services are benefiting patients by improving their liver function and reducing hospitalizations. Getting to know patients and initiating a comprehensive and integrated treatment plan earlier in the disease process greatly facilitates transplant care if patients end up requiring it. Our clinic was formed in 2018 with the guidance and approval of transplant internal medicine and psychiatry leadership. It continues to grow and integrate itself ever deeper into the health system and other related institutional multidisciplinary addiction initiatives. This is the general schedule for the new patient evaluations in this co-located clinic. Each patient stays in an exam room while the team rotates in and out over the course of the morning, evaluating as much of the patient's medical, psychiatric, and social histories and symptoms as possible in a single morning. The team repeatedly conferences and coordinates in the team room between each visit, making the evaluation a dynamic enterprise, which is immediately personalized to data from each team member's examination. The clinic morning ends with wrap-up, final treatment planning, and the patients going to the lab. Perhaps one of the best representations of the integrated and co-located nature of this clinic are the patient education materials. This booklet that we provide to every patient and we authored ourselves reveals how seamlessly integrated hepatology and psychiatric services really can be. As these pages show, patients are guided through practical information about their liver health, diet, and medication management, which then connects seamlessly to practical information about alcohol, cycles of habit, human emotion, decision-making, and coping skills. If we do our job right, our patients cannot really ever separate where their liver care stops and their psychiatric care begins. And this is precisely as it should be for so many diseases commonly encountered by hepatology. Thank you. Hi, my name's Amanda. I am a transplant dietician at Rush University Medical Center in Chicago, Illinois. Here we do kidney, liver, and pancreas transplants, but today I am going to focus on nutrition in patients with cirrhosis. I have no disclosures. The objectives are going to be to determine the effects of malnutrition in patients with cirrhosis, review nutritional needs of patients with cirrhosis, and to understand the importance of dietary assessment and counseling. So a lot of the time on rounds or in clinic, I'll hear that this patient's really malnourished or this patient is very sarcopenic or they're very frail, but I think that that terminology means the same thing to a lot of people, so I wanted to review the definitions of that. So malnutrition is a physical state of unbalanced nutrition. So this could be overnutrition. You can eat more, taking more calories than your body needs, however, still have deficiencies in areas, or it can be undernutrition where you're just not meeting your needs. Sarcopenia is a generalized reduction of muscle mass and function due to aging or acute or chronic illness. So muscle mass would be measured by something like CT scans and muscle function would be measured by something like hand grip strength, but you technically can't diagnose sarcopenia without both. And lastly, frailty is a biological syndrome of decreased reserve and resistance to stressors resulting from a cumulative decline across multiple physiological systems and causing vulnerability for adverse outcomes. So this is something we pay close attention to in the pre-transplant world, considering a long liver transplant is quite a stressor on the body. So malnutrition is inadequately addressed in most patients with acute decompensation, and it can be exacerbated by prolonged periods of NPO while they're admitted or just unpalatable diets, even while they're at home. We know that malnutrition is associated with worsening hepatic encephalopathy, ascites, variceal bleeding, lower quality of life, and higher rates of hepatic decompensation and poor wound healing. And in the liver transplant world, we know that patients spend a longer time on the mechanical ventilator, longer ICU and hospital stay, increased incidence of infection, and overall 12 month mortality after transplant. This is just a table and the columns discuss some or represent some contributions to potentially why patients with cirrhosis are malnourished. And one, we have a big one is that the liver plays a key role in macronutrient metabolism. So we often see an increase in gluconeogenesis or insulin resistance, increase in lipolysis or fatty acid oxidation, a low branched chain amino acid to aromatic amino acid ratio, definitely an increase in metabolism and resting energy expenditure. And then we know that there is a reduction in glycogen stores. A lot of the time we experience a lot of just reduced intake or prolonged fasting in these patients. And that could be from early satiety after they do eat something because of their ascites or just a poor appetite in general. They have, a lot of them experience nausea, vomiting, maybe they're having a GI bleed where they're not able to eat. If there's any sort of altered sleep-wake cycle or impaired consciousness that can contribute to them eating less, unpalatable diets that we discussed, low sodium, any taste changes, socioeconomic status. And we know that there's an increase in anorexigenic hormones in this population. If there's any sort of cholestatic disease, they may be eating, but maybe not absorbing due to bile salt insufficiencies or just pancreatic insufficiency and something going on with the gut. And then lastly, the reduced activity. A lot of the time we think of this more of a sarcopenia or free LT. However, fatigue and weakness can be a huge contributor to reduced functional status in itself. Maybe they're experiencing shortness of breath, they have an amputation that they just don't feel comfortable experiencing or exercising. And a lot of the time it just is out of fear that they aren't strong enough to do their normal activities of daily living that they used to do. And sometimes it's family's fear that they don't let them. So they're doing everything for the patient and not letting the patient even get up and do any tours or go get their own food or anything anymore, which can be further leading to that sarcopenia or frailty. So there are two guidelines that discuss the energy needs for patients with cirrhosis. European Society for Parental and Internal Nutrition state that patients with well-compensated cirrhosis require between 25 and 35 calories per kilogram per day and up to 1.5 grams of protein per day. If patients have decompensated cirrhosis that can increase their resting energy expenditures. So their calorie requirements jump up to 30 to 40 calories per kilogram and up to 1.5 grams with a minimum of 1.2 grams per kilogram per day of protein. And I just wanna note that typically the only time that we restrict fluid despite patient's understanding about this is when they have significant fluid overload and experiencing hyponatremia. The European Association for the Study of Liver also has similar guidelines. They state 35 calories per kilogram, but I wanna note that this is on patient's actual body weight as well as SPINs. So we need to adjust for the fluid that they're carrying, especially ascites. And similarly, the 1.2 to 1.5 grams per kilogram per day of protein. They do note that we should try to shorten nocturnal fasting. So we're including a bedtime or a late evening snack here and making sure that these patients are not skipping breakfast. Cause a lot of the time I will hear that, I typically am not a breakfast person or I don't eat breakfast. However, that's just prolonging their fasting state. Doubly labeled water is not necessarily available to a lot of transplant centers outside of, or hepatologists outside of a research setting. So indirect calorimetry should be used to determine their resting energy expenditure whenever possible, because predictive equations can either over underestimate these patient's needs. So what does this look like for a patient that weighs about 75 kilograms? So that means that they're having two eggs, some sausage in the morning, a whole piece of toast with butter on it, a full sandwich and something with the sandwich, such as an apple and peanut butter, and then maybe a fairly large chicken breast with a full baked potato, butter and vegetables on the side, including a snack and some liquids. And these are three fair sized meals with some calorically dense food in them. And this is only getting to the patient to 29 calories per kilogram. However, it is meeting their protein needs. But from doing countless diet recalls in this population, a lot of the time I'll experience, maybe I'll have an egg and a couple of bites of my toast in the morning. Hours later, they can fit in, maybe half of a sandwich. And if they're lucky, they'll have something about the size of one steak taco, and maybe an oral nutrition supplement that someone told them to drink throughout the day. And this is only meeting 13 calories per kilogram, and not even the standard protein dose for a healthy patient of 0.8 grams per kilogram. They're only at 0.7 with this intake. This does change a little bit if you have a patient with fatty liver or NAFLD or NASH. The recommendations are typically weight loss. So we recommend seven to 10% to help improve steatosis, and greater than 10% to improve any fibrosis. So we typically do this in a 500 to 800 calorie per day deficit with adequate protein to make sure that these patients are not losing, potentially losing weight, but maintaining their muscle mass. Or you can base their calorie recommendations on their ideal body weight. Any hypochloric diet, regardless of macronutrient composition, has been shown to be beneficial. And the Mediterranean diet is typically recommended to improve fibrosis and insulin resistance. However, I will tell you that if you just give your patient a handout or you just tell them to follow the Mediterranean diet, it's quite unlikely that by the time their next clinic visit comes around, they'll be following it pristinely. It's kind of difficult, involves a lot of food, and a lot of the time these patients just can't fit it in. Patients should always screen for type 2 diabetes, and coffee consumption is thought to be beneficial. However, this does not mean lattes or cream and sugar, because we're trying to reduce high fructose corn syrup and sugar-sweetened beverages. Of course, oral intake is the preferred route for nutrition. And if patients can't meet their needs orally, oral nutrition supplements, like we just discussed, can be added to the mix to increase their calorie, their protein intake. But if patients can't meet their needs or are unlikely to resume PO within the next five days, let's say they're admitted, enteral nutrition should be considered or started because it's cheaper, has a lower infection risk, and less complications compared to parenteral nutrition. Do you want to know that a Dobhoff is considered safe in the presence of non-bleeding varices? And ascites is not necessarily an absolute contraindication to a PEG tube, but it's typically avoided due to increased complications like a buried bumper. There's not necessarily research out there to state that patients with cirrhosis need any specific formula, so a lot of the time they do well with just a standard concentrated formula, so 1.5 calories per milliliter versus a one cal per milliliter formula to just to reduce the volume that they need to intake. And lastly, last line of resort is parenteral nutrition. So this is for patients that do not have adequate GI function, the gut's not working. It's gonna be an ileus or a small bowel obstruction or an active GI bleed. But when patients are on parenteral nutrition for their source of nutrition, you wanna monitor the trace minerals, specifically manganese and zinc, because they are excreted in the bilirubin or in bile. So if the bilirubin is trending upwards or it's high, we typically want to remove the trace minerals or specifically these two from the mix. And we always wanna titrate to less than 18 hours per day to prevent further liver injury. So why do these patients need dietary assessment and counseling? Why is it so important? So there was a study that looked at a retrospective part and a prospective part. And prior to educational intervention to involve nutrition professionals sooner in the care of hospitalized patients with cirrhosis, they found that patients had a longer length of stay and 90 day readmission rates. After they completed the education with the professionals caring for the patients, they found that there was an increase in nutrition consults, higher protein and more frequent bedtime snacks, significantly more vitamin supplementation, lower length of stay and readmission rates. So in 1994, a study came out saying that up to 50% of patients with decompensated cirrhosis were found to be malnourished. And a more recent study even 2019 found that up to 95% of patients with decompensated cirrhosis with Child's Pew score of C. So almost 100% of patients were found to be malnourished. So this is highly occurring highly and nutrition professionals should be involved because we know that the liver plays a key role in macronutrient metabolism and micronutrient storage. So just the metabolism in general is not considered normal. Oral nutrition supplements or enteral and parenteral nutrition are often required to help patients meet their needs. And this means longer term management. And I think a huge part of this is that patients and families, the stressors that come with weight loss or reduced oral intake in this population can sometimes be too much for them to deal with. So it's really important for a dietician to sit down and discuss the expectations, how to achieve their nutrition intake appropriately, et cetera. And obesity is present in 20 to 40% of patients with cirrhosis so this can mask the ability to truly identify malnutrition unless we're doing something like a nutrition focused physical exam or diving deeper into the details of their lifestyle. This table kind of mirrors the table that I had talked about earlier and that just has some interventions to deal with what the issues are. So with the ultra macronutrient metabolism over here on the left, a lot of the time we're trying to enforce small frequent meals if their appetite's poor, encouraging a bedtime snack to reduce that prolonged fasting. However, the protein intake for these patients, you saw that it was quite high, the 1.2 to 1.5 grams per kilogram per day. We wanna encourage them to eat the protein source first if they really just don't have a great appetite because we need them to get that protein in to help maintain their muscle mass. A lot of the time, oral nutrition supplements are required. However, they can differ between patients. So maybe a patient has a protein aversion but otherwise they're eating well, they're eating their carbs, even their vegetables. Maybe we just need to encourage them to have a lower calorie but higher protein supplement when they don't need the extra calories or they just have a really poor appetite, they can't maintain their nutrition intake, they're barely eating, then we would go for the nutrition supplements that are higher in calories, higher in protein to get the most bang for our buck. And honestly, a lot of the time, I'll encourage patients to eat something as opposed to nothing because we had already talked about the sodium restriction unpalatable diets can lead to further worsening malnutrition. So if a patient's been in a doctor's appointment all day and they're too tired to cook when they get home, I would rather them stop somewhere and pick up a burger with some carbs and some protein as opposed to them not eating for the rest of the night because they're too tired to make it. And going to the second column, reduced nutrient intake. A lot of the time that patients can tolerate liquids as opposed to like full foods, it helps move the GI tract faster, it helps make them not feel so full for so long. So smoothies with additives such as peanut butter, high calorie foods, whole Greek yogurt, whole fat Greek yogurt, things like that can be used to really increase their dietary and nutrition intake. However, it doesn't keep them as full so long. And then the reduced activity all the way on the right side is often an issue that we run into. And so you need to help encourage patients if they can safely do it to complete their activities of daily living, just to clean their dishes after they're doing it. Maybe you can help sweep or mop. A lot of the time patients require a physical therapy referral. And a lot of the time, like I mentioned before, their family members are the ones that are too nervous for them to be participating in these activities. So maybe there just needs to be a discussion that patients can be doing some things around the house with assistance or supervision as opposed to not doing them at all. So it's important to educate the patient and family members on things like this. This is just a table that has a little bit more information on it, but for time's sake, I'm not gonna go through it, but it states some problems like maybe they're consuming a high sodium diet, inadequate nutrition, like we talked about, not doing physical activity. They have different GI side effects. It lists some of the causes for these problems and then what some solutions are to address them. And lastly, I just wanna note that all of these interventions are typically trial and error. Each patient is different and they have their own preferences and their own lifestyles. So we need close and consistent follow-up for patients, especially when they're high risk to work on different interventions. Maybe they don't like certain protein sources and we need to find different ones. We give them a suggestion and it didn't work for them. We need to follow up with them again to make sure that we can find something to help them meet their needs and prevent worsening malnutrition, sarcopenia or frailty. And I know that this was a topic of discussion from a dietician about nutrition. However, I cannot stress enough that multidisciplinary management to prevent or address malnutrition in these patients is absolutely crucial. We need help with things like medication prescriptions, like an appetite stimulant or pancreatic enzyme replacement. We need potentially labs ordered. Maybe we think that someone has a vitamin deficiency or even a toxicity. And then referrals for physical therapy often need to be placed. And again, just reiterating education that the dietician provided and making sure that the patient hears it from their hepatologist or someone else on the team so they know how important it is that they need to be doing in these interventions that they discussed in their visit this day. But with that, that is it. And I'm happy to answer any questions that you have. Hi, my name is Annalise Nolan. I'm a specialty practice pharmacist specifically in solid organ transplant at The Ohio State University. And today as part of this program, I'll be talking about the pharmacist role and in particular what you put in your mouth, your liver sees. I have no disclosures related to this presentation. The objective of this presentation will be first to review the pharmacist's role in the management of patients with liver disease and talking about some of the changes that occur in these patients to discuss the safety of over-the-counter as well as herbal supplements and cirrhosis. And finally, I'll be discussing some of the medications that should be avoided in patients who have cirrhosis. So starting out talking about the role of the pharmacist. Pharmacists play a key role in the management of patients with liver disease, in particular ensuring safe and effective use of medications in these patients. The reason that this is especially important in patients with liver disease is that liver disease can cause alterations in one of our pharmacist's favorite mnemonics, ADME, right? So absorption, distribution, metabolism and excretion. So in the little picture you can see here, you have probably reviewed this in the past. So absorption, we're actually absorbing the medication, distributing it through the body, metabolizing or breaking it down and then excretion or elimination of the drug. So all four of these pathways can potentially be affected. Starting out first with absorption, there are GI changes that can occur in cirrhosis that can change the rate and extent of drug absorption. In particular, things like portal hypertensive gastropathy, GI ulcers, increased intestinal permeability, as well as things like impaired GI motility with delayed gastric emptying can all affect the absorption of medications with liver disease. In addition, altered blood flow, such as if a patient has tips or protosystemic shunts, as well as reduced intrinsic clearance can affect first pass effects as well as the metabolism of prodrugs. Distribution of medications can be affected in a couple of ways in patients with liver disease. First, we've got decreased plasma proteins like albumin because of impaired synthesis by the liver means that especially highly protein-bound medications will have a larger fraction of unbound drug. In addition, endogenous substances like bilirubin can actually displace the binding sites on protein, so affecting the amount of free drug. And the second thing to consider is that you end up with increased volume of distribution in these patients due to food retention in the CITES. So essentially that's going to affect the concentrations of medications in the bloodstream when you increase that volume of distribution. Metabolism can be affected in a few ways. And when we often think about the liver, we think about drug metabolism. So in particular, altered hepatic architecture, so this includes things like necrosis, altered blood flow, hepatic nodules can reduce the expression of your drug metabolizing enzymes. It is important to know that the extent of reduced activity of these enzymes will vary sort of based on the enzyme. So for example, CYP2C19 is really sensitive to changes while others such as CYP2D6 aren't as affected until later on in liver disease. And in addition, reduced blood flow across the liver due to cirrhosis can result in delayed medication clearance as well. Finally, excretion, so eliminating the medication from the body or its metabolites. So first, if the patient has any sort of bioflow obstruction such as cancer or PSC, we can end up with decreased biliary excretion. In addition, we can end up with disrupted enteropathic recycling due to reduced protein transporter expression. And finally, if the patient has renal impairment due to hepatorenal syndrome, we can end up with reduced renal elimination of medications as well. When we look at all these changes, the important things to consider is that if you're dosing medications in a patient with cirrhosis, it's really important to review dosing recommendations. And these are usually pretty easy to find, you know, use your favorite reference and resource in terms of dosing adjustments in determining if medication needs to be changed. And not necessarily every medication needs to be adjusted for cirrhosis, but it's always good to double check. In addition, it's important to consider what underlying conditions associated with cirrhosis the patient may have when you're choosing medications to use. And this is going to apply to herbal supplements as well. So for example, if a patient has, you know, hepatic encephalopathy and you've got medications that are perhaps associated with neurological side effects, that'd be something you want to avoid. In addition, medications that could increase bleeding risk could be a problem in a patient who perhaps already has, you know, problems with an elevated INR due to their liver disease. Moving next to talk a little bit about over-the-counter or OTC, as well as herbal supplements. Now this is a big business. A recent survey that was published demonstrated that 57.6% of adults use at least one dietary supplement and the rate or the number of supplements used actually often increases with age of the patient. It's especially important to know about these medications being used in particular because of the regulation or rather lack thereof of these medications. The FDA regulates supplements as foods rather than as drugs. And so this basically means we're assuming them to be safe unless proven otherwise. It's also important to note that while these medications are prohibited from making medical claims, supplements can make non-specific claims such as, you know, enhanced energy or as we'll get to in a little bit, liver savior or whatever, which can be, you know, of course confusing for patients and these aren't proven by any means because they're not required to, you know, prove those medical claims. So a question that I get asked probably once a day is, can my patients start, you know, XYZ herbal supplement? And I don't always say no, although the running joke is that I do, but the bigger questions that I have whenever I'm asked the question, if a patient can start an herbal supplement is first, why do they want to take it? What's the reason? Are there, you know, potentially more safe options out there that they want to take this medication for? So the first question to always ask is, well, why do you want to start this medication? What's the reason? Can we find maybe an alternative that may be safer for you? Next is, you know, what are the benefits of this medication? We know that some, you know, supplements or vitamins, things like that would be beneficial to the patient. And on the flip side is what are the risks? So what are the risks of these herbal supplements? Are there side effects associated with them? Are there potentially drug interactions we should be worried about? To answer these questions, one of my favorite resources will be listed here on the next slide. So there's a couple of resources I've listed here. So the National Institutes of Health Office of Dietary Supplements, Natural Medicine Database, and as well as Liver Talks, which is a publication, the link is here on the screen, to the NIH, which is a great resource to look up information that's been published about a ton of different supplements, whether or not they're beneficial and what the sort of risk of potential hepatotoxicity is associated with those medications. The reason I particularly mention hepatotoxicity is because this is one of the, you know, biggest concerns we have with the use of herbal supplements. On this slide, what this image shows is the results of a recent review that looked at the use of hepatotoxicity with herbal or dietary supplements. What they found was that actually 20% of the drug-induced liver injury in the United States is due to herbal or dietary supplements. It can get tricky to nail down exactly what the problematic entity is causing the problem because often it's multi-ingredient products implicated. However, the most common by far is going to be these top three things. So medications for bodybuilding, so trying to, you know, build up muscles, anabolic steroids, for example. Another big problem is going to be medications used for depression and then weight loss medications have also, and you may have seen this in the news as well, about different weight loss medications causing hepatotoxicity. On this next slide, I list a couple additional agents that weren't mentioned on the previous slide, but like I mentioned, far and away, the bodybuilding supplements are a concern. The weight loss agents, what's often been tracked down to with hepatotoxicity is the use of green tea extract in these agents. Herbal blends, botanical mixtures, things like this can be listed as well. And when a patient is taking, you know, a blend of herbs and they develop liver toxicity, it can be really hard to tell which agent caused it. A couple agents that they've changed since, but Herbalife and Hydroxycut, a couple other listed here, Kava, Germander, Black Cohosh, and many more medications have been implicated. Like I mentioned, what makes it tricky is that these medications aren't necessarily regulated, so we don't always know what's in them when a patient does, you know, present with hepatotoxicity. Besides the risk of hepatotoxicity, the other big concern I have, especially as a pharmacist, is with drug-drug interactions with the use of herbal medications. Luckily, some medications, herbal supplements, we definitely know the interaction, but a lot of times we don't necessarily know. So what I always caution about is if a patient is on a medication that could potentially have a very bad effect, you know, if the level of that medication were to increase or decrease, that'd be definitely something to avoid. So what I mean by this is, for example, if a patient is on a blood thinner like warfarin or aspirin, if they are maybe a transplant patient on immunosuppression with tacrolimus, like Lisporin, if they're on protease inhibitors, HIV medications, or really anything that's metabolized through CYP3A4, which is going to be a lot of your medications, can have huge implications, right? So if you're on a blood thinner like warfarin and you're started on herbal supplement that increases your INR, you could potentially end up with a devastating bleed. Or if you're a transplant patient on tacrolimus, you start an herbal supplement that makes your tacrolimus level go undetectable, you could end up with rejection. So sometimes patients, you know, kind of assume that herbal supplements may be safe or that won't affect their other medications and don't think about kind of the downstream effects of starting these herbal supplements. So it's always really important to have that discussion with patients, you know, rather than just being like, nope, you can't take this medication, but explaining, you know, it could make you bleed, this could, you know, you could have rejection of your transplant, things like that sometimes make it a little bit easier to understand in someone who really is insistent on taking an herbal supplement. Next up, we have our case. MS is a 42-year-old male with history of alcohol-related liver disease. Current medications, pretty much what we'd expect, he's on spironolactone, furosemide, a multivitamin, and pentoprazole. And he sends you a message in your electronic medical record. He wants to know, hey, will these fix my liver? And he sends you a whole bunch of different potential medications he's found on the internet. So we've got liver cleanse, urgent liver, 911, liver refresh. And the question is, are these going to fix me? Because these labels look pretty convincing. You know, these look like they could be something good for me. So going back to our questions of what do you want to use it for? Is it safe? What are the potential interactions? So in this case, it's pretty clear. He's hoping that this may fix, you know, may fix his liver. But one thing to point out about the medications listed on this screen is that a lot of them seem to be combination herbal products, which I'd mentioned previously. We want to avoid because we don't necessarily know what's in them. But in particular to our liver patients, milk thistle is the sort of predominant active ingredient in these agents. So we'll say, okay, we'll talk about this. Let's talk about milk thistle. So is this safe? So what I mentioned before, whenever I'm asked a question about an herbal supplement, is it safe? Step one, we'll check liver tox. So I go to my computer, type in milk thistle, and this is what the screen's going to look like. And I don't expect you to be able to read this, but there's a lot of information about the medication in particular, the safety, potentially what data is associated with or without with hepatotoxicity with this medication. So per liver tox, milk thistle has not been implicated in causing serum enzyme elevations or clinically apparent liver injury. And then silymarin, which we'll talk about, the active ingredient has effects on P450 enzymes, little evidence it causes drug interactions. And then they also will give you a likelihood score that it's an unlikely cause of apparent liver injury. So liver tox makes me feel confident. I think we're okay that this medication probably won't be harmful to the patient. So the question is, will it be beneficial to you? And so this is really a medication you'll commonly see in these ingredients for these herbal products to kind of, you know, fix the liver, liver cleanse. And it's actually a medication that's been around for centuries. So silymarin is the extract from the milk thistle seeds. And there's a lot of really interesting papers that look at this medication, finding it has antioxidant, anti-inflammatory, antifibrotic, antiviral properties. What's sort of tough though, is that well perspective or well-controlled prospective studies are lacking. There have been some control trials in hepatitis C and NAFLD that really found little to no benefits. There have been some smaller studies showing mixed benefits, but overall sort of hard to say whether or not it's a slam dunk to use this medication. What makes it sort of tricky is that it's got really poor oral bio availability. And so a lot of the oral formulations that we take don't necessarily have, you know, great, great drug levels in your body. One thing to note, and you may have seen this in clinical trials as well, that there are IV formulations used of this medication for Amanita mushroom poisoning. And this is actually approved in Europe, not in the United States, but definitely something to keep an eye on. Back to our patient, he's asking about starting milk thistle. So it probably won't be harmful, may have benefits. I would recommend to not use one of those combination products. But I think this is something that he could try if he's interested in it. But the other question I have is what else might be of benefit to this patient if we're talking about over-the-counter medicines, herbal supplements? So a really great guidance paper was just published this year in hepatology is the malnutrition, frailty, and sarcopenia in patients with cirrhosis practice guidelines. And in particular, these guidelines are going to have recommendations for monitoring some certain supplements for these patients. So in cirrhosis, we know that there are high rates of micronutrient deficiency. In alcohol-associated liver disease in particular, due to either malabsorption, we see vitamin D deficiency, vitamin E, folate, thiamine, zinc, and selenium. Zinc in particular can be problematic because zinc is a cofactor in the urea cycle that metabolizes ammonium. And so you can have associated with hepatic encephalopathy with deficiency with zinc. In addition, in patients with cholestatic liver disease like PBC, for example, fat soluble vitamins can be deficient. We know that deficiencies in the micronutrients as well can be associated with frailty or sarcopenia. So it's important to keep an eye on. And in fact, that paper that I just showed, the guidance statement is that micronutrient deficiencies should be assessed at least annually, repleted if deficient, and reassessed after repletion. And what's great about that guidance paper is it actually has dosing recommendations for micronutrient supplement as well as monitoring. So it's a great resource to look at if you've got someone who you're just screening for micronutrients, wondering about the dosing recommendations. Great first place to start. So back to our patient, given his history of alcoholic liver disease, he's at risk of micronutrient deficiency. So we'd recommend to screen him for deficiencies. And then perhaps we could recommend if he wanted something beneficial over the counter to help, perhaps something like vitamin D if he's deficient in it. That'd be a good place to start. I just want to close with a couple of things to think about. First, always make sure you complete a thorough medication history. Oftentimes, patients don't necessarily think of supplements as part of their medication list. And so it's important to ask that question in particular if they're taking any herbal supplements, because as I mentioned, this could have major implications for the patient. In general, I prefer to use single agent versus combination supplements. With the lack of regulation, it can be tricky, but at least if we are avoiding combinations, we can sort of narrow down what the active ingredient is. And I always say when in doubt, just say no. Risk benefit can be tough, but we would hate to have the patient be harmed by an herbal supplement they thought would benefit them. So when in doubt, just say no. In conclusion, it's really important to carefully evaluate medication dosing in liver disease patients. We should always be mindful of hepatotoxicity risk with herbal supplements. And finally, making sure reviewing these updated guidelines, knowing that patients with cirrhosis may benefit from micronutrient supplements. And thank you very much. My name is Karen Strenger. I am a physician assistant in transplant hepatology, working inpatient at MedStar Georgetown University Hospital. Today, I am going to talk about acute on chronic liver failure or ACLF. This is something that I commonly see and manage in the inpatient setting. I have nothing to disclose. I'd like to start off with a case study. The patient is a 34-year-old female with decompensated hepatitis C cirrhosis admitted to the hospital with worsening jaundice and ascites with a MELD score of 20. In the emergency department, she undergoes a diagnostic paracentesis that reveals 500 acidic neutrophils consistent with spontaneous bacterial peritonitis. She is initiated on prompt treatment with ceftriaxone, two grams IV daily, as well as an albumin infusion. Blood cultures collected on admission grow E. coli, which is sensitive to the ceftriaxone. A repeat paracentesis after 48 hours shows a 50% reduction in the acidic neutrophil count. However, despite her response to the treatment for SVP and E. coli bacteremia, the patient deteriorates clinically. She develops increasing hypoxia with a new oxygen requirement, and she develops grade four hepatic encephalopathy. Ultimately, the patient requires transfer to the ICU for increasing hypoxic respiratory failure, requiring intubation and ventilator support. She undergoes a repeat infectious workup due to her clinical decompensation. A chest CT reveals a new hospital-acquired pneumonia. Repeat cultures demonstrate no growth. The patient is placed on broad-spectrum antibiotics for hospital-acquired pneumonia. In the setting of this worsening illness, the patient also develops a rising MELD score. It goes from 20 up to 32. Initially, she had SVP and E. coli bacteremia, but now she has a new superimposed hospital-acquired pneumonia with respiratory failure and worsening encephalopathy. This case raises a lot of good questions that I'm going to address during the talk. What happened to this patient? Does she have ACLF, and is it appropriate to consider transplant for her? To answer those questions, first, we are going to define ACLF. Then we will talk about how ACLF can be differentiated from acute decompensated cirrhosis, or AD. We will talk about the diagnostic criteria for ACLF. We will review some of the tools to predict prognosis in ACLF. We will discuss therapeutic management of ACLF, and finally, go over the role of transplant in this condition. It turns out that defining ACLF isn't so simple. There are multiple definitions provided by major international scientific societies, ESL, APOSL, and NAXL. This table shows some of the variations in the definitions. I would like to highlight some of the key differences. Definitions include different stages of underlying liver disease, ranging from non-cirrhotic chronic liver disease all the way to decompensated cirrhosis. Definitions encompass different precipitating events, intrahepatic only versus intrahepatic and extrahepatic events like sepsis. Also, various definitions include different criteria to define organ failures and different exclusion criteria, such as HCC or other malignancies. Part of the reason for the varying definitions is that there is geographic variation in the cause for ACLF. In the West, bacterial infections and active alcohol intake are the most common precipitants. In the East, the most common precipitants are hepatitis B flares, followed by sepsis and active alcohol intake. Because of all the different definitions for ACLF, it has been difficult to study the prevalence of this phenomenon. It is estimated that approximately 30% of patients with cirrhosis admitted to the hospital are affected by ACLF. In 2014, the World Gastroenterology Organization attempted to come up with a consensus working definition for ACLF. They defined it as a syndrome in patients with chronic liver disease with or without previously diagnosed cirrhosis, characterized by acute hepatic decompensation resulting in liver failure, jaundice and prolonged INR, as well as one or more extrahepatic organ failures. Additionally, ACLF is associated with an increased risk of mortality within a period of 28 days and up to three months from onset. So, how can we differentiate acute decompensated cirrhosis or AD and ACLF? Well, AD refers to the development of ascites, hepatic encephalopathy, variceal bleeding, or any combination of these in cirrhosis. Whereas ACLF is a distinct condition, which is associated with liver failure, as well as single or multiple extrahepatic organ failures, which we will define in just a few slides, and high short-term mortality in excess of 15% at 28 days. ACLF is pathophysiologically distinct from AD. It occurs in the context of severe systemic inflammation. It's associated with high white counts and C-reactive protein levels, and it frequently develops in close relationship with pro-inflammatory events, such as alcohol-associated hepatitis or sepsis. The canonic study performed by the Easel-Cliff Consortium was the first major study to identify diagnostic criteria for ACLF. The study was a large observational study that looked at over 1,300 patients with cirrhosis hospitalized for various acute decompensations. The study established diagnostic criteria for ACLF based on analyses of patients with organ failure and high 28-day mortality rates. To diagnose organ failures, the canonic investigators adopted the Sequential Organ Failure Assessment, or SOFA score, which is widely used to diagnose organ failure in general ICUs, and they modified it to account for specific features of cirrhosis, calling it the Chronic Liver Failure SOFA score, or the CLIF SOFA score. This was later simplified into a newer version, called the CLIF Consortium Organ Failure Score, or CLIF-COF, which is what you see represented in this chart. It includes six major organ components, with higher scores indicating more severe organ impairment. The values in the darkest green shade correspond to diagnostic cutoffs for organ failure. Liver failure is defined by a serum bilirubin of 12 or greater. Kidney failure by a serum creatinine of 2 or higher, or the use of renal replacement therapy. Cerebral failure by Westhaven grade 3 or 4 hepatic encephalopathy. Coagulation failure by the use of, sorry, by INR of 2.5 or higher. Circulatory failure by the use of pressors, and respiratory failure defined by specific ventilator settings. This scoring system allows for organ failures in ACLF to be universally defined by specific criteria. Once the organ failures have been identified, ACLF can be graded depending on the number of organ failures that are present. The no-ACLF group consists of patients without organ failure, or who have single non-kidney organ failure or encephalopathy. ACLF grade 1 includes patients with single kidney failure, patients with non-kidney organ failure plus kidney dysfunction and or brain dysfunction. ACLF grade 2 is patients with two organ failures, and ACLF 3 is patients with three or more organ failures. It's important to note that even mild renal dysfunction or encephalopathy in the presence of another organ failure is associated with significant short-term mortality and therefore constitutes ACLF. Many patients with liver disease admitted to the hospital fall into this category. This graph from the Canonic Study shows mortality rates according to grade of ACLF. The more organ systems failing or the higher the grade of ACLF, the higher the patient's mortality rate, both at 28 and 90 days. The 28-day mortality rate among ACLF patients ranged from 23 to 74 percent, depending on the number of organ failures present. In comparison, for those with simple AD without ACLF, 28-day mortality was less than 2 percent. For patients with three or more organ failures, mortality approached 80 percent at 30 days, even with maximal ICU support. This figure demonstrates the Kaplan-Meier 90-day transplant-free cumulative survival curve of patients in the Canonic Study with traditional AD, shown in green, and ACLF, shown in red. This reveals significantly poorer outcomes among patients with ACLF compared to those with traditional AD. The two curves separate very early into the hospital course, which underscores the idea that ACLF is a distinct phenomenon with a markedly worse prognosis than traditional AD. It's important to understand that ACLF is a dynamic condition, and it can improve or worsen over time. One study published in the Journal of Hepatology in 2015 looked at 388 patients with ACLF. For half of all the patients, ACLF resolved or improved during the hospitalization. As expected, the frequency of ACLF resolution was highest in patients with initial grade 1 ACLF and lowest in those with initial grade 3 ACLF. The best time point to define the clinical course of ACLF was between days 3 and 7 after diagnosis. In 81% of patients, the final grade of ACLF was already defined at days 3 to 7, resulting in accurate prediction of short- and medium-term mortality. ICU care of patients with ACLF should be continued during the first seven days after ACLF diagnosis. Assessment at day 7 can help us make decisions regarding subsequent management, whether it makes sense to continue care and try for a liver transplant or discontinue care owing to futility. Earlier, we looked at the CLIF-COF score to define the diagnostic criteria for organ failure. When this score is combined with two independent variables that predict mortality, age, and white blood cell count, it's used to generate the CLIF-CACLF score, which ranges from 0 to 100. The CLIF-CACLF score outperforms MELD and Child's Pew in predicting 28-day mortality because it accounts for all of the extrahepatic organ failures that have a significant impact on prognosis. This graph is from a 2018 study that was set up to determine if there is a cutoff in ACLF for which prolonged ICU care is likely to be futile despite maximal treatment efforts. 202 patients with ACLF were analyzed 48 hours into their ICU stay. A CLIF-CACLF score cutoff greater than 70 identified patients with 100% mortality at 28 days. The red bar that you see on this graph represents that CLIF-CACLF score threshold above which the futility of care should be considered. Unfortunately, to date, there is no specific therapy for ACLF. Management focuses on treating precipitating events and managing organ system failures. It is important to treat any underlying infections, start early antibiotic therapy, and then later tailor the therapy to culture and sensitivity data. In alcohol-associated hepatitis, consider the use of steroids after ruling out infections, of course, but have a low threshold to stop the therapy if there is no improvement after one week. Treat hepatitis B flares when indicated if those are precipitant for ACLF and, of course, address any variceal bleeding with resuscitation, antibiotics, and early endoscopic evaluation. While it's helpful to treat all of these precipitants, in up to 43% of patients in the canonic study, there was no identifiable precipitating event. It may be related to bacterial translocation from the gut, but this is not entirely clear. I'm going to highlight some of the key points for the general management of ACLF by organ system. In the kidneys, you want to avoid nephrotoxins, treat for hepatorenal syndrome with albumin, enterolipresin, or levophed, and use renal replacement therapy as a bridge to transplant. For the hemodynamics, you want to aim for MAP goals greater than 65, volume expand the patients with albumin and crystalloids. You can use levophed as your first-line presser and consider IV hydrocortisone and refractory shock. For lungs, have a low threshold to intubate for airway protection in grade 3 or 4 encephalopathy and use lung protective ventilation strategies. For the central nervous system, avoid benzos and sedating medications. For coagulation, avoid correction of INR with FFP in the absence of any overt bleeding. For GI support, start stress ulcer prophylaxis and tube feeds for nutritional support. These are some of the basic guidelines for principles of treatment in ACLF. This is a visual representation of the window for liver transplant in ACLF patients. The horizontal axis is time, and the vertical axis shows the patient's clinical condition. Initially, if the patient's status is stable, it may be too early to consider them for transplant. But as their condition worsens, they will reach a crossroads. Either they will have some recovery from the ACLF and stabilize to a point that transplant is appropriate, or they will continue to deteriorate, but not to a point that reaches the futility limit for transplant. The appropriate timing for transplant is either when they clinically improve or deteriorate to a point that is above the futility limit. Early referral to a transplant center is critically important so that transplant workup can be started before patients become too sick and reach the point of futility. This graph is showing you the probability of staying alive on the wait list for more than 30 days without a liver transplant based on the number of organ failures in ACLF. For those patients with three or more organ failures, survival at one month without transplant is less than 8%. So, the window for transplant is pretty small. It's important once you've stabilized these patients and controlled their infections to run the risk of a transplant. Once you've stabilized these patients and controlled their infections to rapidly evaluate and prioritize them for transplant. Looking at transplant in ACLF, this is a study that was published in 2018 that looked at 3,500 patients with three or more organ failures at the time of liver transplant. Although the risk of post-liver transplant mortality increased with increasing number of organ failures, one-year survival was 81% even in the setting of five to six organ failures. At five years post-transplant, survival ranged from 67 to 73% in the setting of multi-organ failure. However, this study did not provide data on morbidity or length of hospitalization. I would be curious to see that data because these patients have much more challenging post-transplant courses and higher complication rates. The takeaway here is that liver transplant is feasible with reasonable survival outcomes, even in the presence of multiple organ failures. This study from the Journal of Hepatology in 2017 looked at 73 patients with grade 3 ACLF that were transplanted after being stabilized. One-year survival of the transplanted patients with ACLF grade 3 was 83.6%. All of the ACLF 3 patients had post-transplant complications ranging from pulmonary to renal to infectious issues, and they also had increased lengths of stay compared to non-ACLF patients. We need further studies to determine the optimal timing and selection criteria for these patients. If we go back to our case study, the patient was initially admitted with acute decompensations due to SBP and bacteremia. She then developed a hospital-acquired pneumonia and worsening encephalopathy with grade 3 ACLF and four organ failures, lung, brain, liver, and coagulation. This gave her a CLIF-C ACLF score of 55 and a probability of dying at one month of 40%. After three days on broad-spectrum antibiotics for hospital-acquired pneumonia and aggressive management of encephalopathy, the patient is actually clinically improved and able to be extubated. She now has ACLF grade 2 with two organ failures, liver and coagulation. At that point, the patient was promptly evaluated and listed for a liver transplant with a MELD score of 30. She was transplanted one week later and is still alive six months after transplant. The key takeaways from my talk today are that ACLF is a syndrome in patients with chronic liver disease characterized by acute hepatic decompensation and one or more extrahepatic organ failures as well as high short-term mortality. Multi-organ failure, high mortality rates, and marked systemic inflammation distinguish ACLF from AD. The CLIF consortium organ failure score can be used to diagnose and grade ACLF. Short-term mortality and prognosis in ACLF can be accurately predicted by the clinical course of the syndrome at days three to seven. Management of ACLF is targeted at treating underlying precipitants and also supporting ongoing organ failures. There is a window for select ACLF patients to undergo liver transplant with acceptable survival outcomes. Further studies are needed to determine the optimal timing and selection criteria for these patients. Thank you so much for listening today and please let me know if you have any questions. Hi, thank you for joining me for my presentation on post-liver transplant care for the community provider. I'm Cori Burke. I'm Associate Professor and Director of the Family Nurse Practitioner Program at Loma Linda School of Nursing and I also serve as Clinical Director at the Las Vegas campus of Loma Linda's Transplant Institute. These are my disclosures and on to my presentation. So, when a lot of clinicians think of liver transplant, they think of the surgery itself and put a full stop on it, but any of us that have cared for liver transplant patients know that it's a continuum. Everywhere from vetting a good candidate, referring them to a transplant center, doing the medical psychosocial evaluation, ultimately listing them for liver transplant, then them getting the surgery for the life-saving organ. However, follow-up is lifelong and that's the area of the continuum that we're going to be concentrating on today. First, we'll go into a little bit about the liver transplant surgery just so as you inherit these patients from the transplant center, you kind of know the verbiage that may be in the note. So, we have two types of liver transplant, cadaveric versus living donor. Cadaveric is from a deceased donor and it's usually a whole liver that gets placed into the recipient. Occasionally, they'll do split livers, but it's usually a whole liver. The living donor comes from a donor who has one of their liver lobes removed and that is placed into the recipient. It has a lot of benefits. You can transplant at a lower meld score when the patient's less sick. The surgery can be scheduled, but they do have their own complications from a living donor liver transplant because you're putting half a liver where a whole liver should be. There's also brain death versus donation by cardiac death. Brain death means that the donor's brain is dead, but the organs are harvested while the body itself is still on life support. Donation by cardiac death means that the liver was taken out of the body once the heart has stopped. You may see domino transplants, which those I find super fascinating. They're done for patients that have familial amyloidosis. Their livers are actually fine, but they get a new liver and then their liver can actually be transplanted into someone else. We usually reserve these transplants for patients who are over 60 years old because they can start to exhibit signs and symptoms of amyloidosis after decades of getting one of these domino livers, so we kind of try to match it up with their life expectancy. The surgery itself usually lasts about six to eight hours, but it can be up to 12 if there's some complications that happen in the OR. The Mercedes incision is the classic incision you'll see. I have it in the two pictures above. If you do an abdominal assessment on anyone and they have this incision, they've likely had a liver transplant. After the OR, they usually go to the ICU. In some lower meld regions, they do sometimes go directly to the floor, and then ultimately, after about seven to ten days, they are discharged from the hospital. They usually are advised to stick around very close to the transplant center in that early post-op period. Just to go over some surgical complications, you likely won't see these because you'll inherit these patients farther out from transplant, but one of the most severe is a hepatic artery thrombosis. This is a clot of the mean blood supply into the liver, and it usually requires emergent transplant. We list these patients as status 1A because they usually have hours or days left to live. The risk for HAT doubles for living donor liver transplant. We also have portal vein thrombosis. This is a clot in the portal vein. This may or may not require retransplant. A lot of times, we just try to anticoagulate this. Sometimes, if patients have this, ascites develops post-transplant. Ascites post-transplant is not normal and needs to be further investigated. These patients can also have a biliary leak or stricture. Biliary leaks are 40% more common in the living donor liver transplant, while only 15% in cadaveric transplants. Once again, in living donor, you're putting half a liver where a whole liver should be. And then the risk of stricture. Stricture usually happens at the anastomosis, and that's the area where the surgeons connect the donor bile duct to the recipient bile duct. It's like sewing two coffee straws together. The incidence of that is higher in the donors that had cardiac death. Bleeding, oftentimes, in about 10% of cases, recipients require an OR take back due to this complication. And then as we all know, infection is always a risk of any surgery. But being a community provider, these are the most common complications you'll see post-transplant. So first and foremost, acute or chronic rejection. A lot of times, I'll get calls and I'll be like, oh, what are the liver numbers? And they give me these really high transaminases, thinking they're normal because, oh, the patient had a liver transplant. Transaminases in the absence of a recurrence of primary liver disease should be normal. And if they're not, it warrants further investigation, usually a liver biopsy if we suspect rejection. As far as biliary stricture, the liver numbers will elevate in more of a cholestatic pattern. And if that's the case, further investigation would need to be done with either ultrasound to look for bildil or MRCP to get a really good visualization of the biliary tree. If stricture is a problem, we can do ERCP, stent that stricture. Therapeutic endoscopists have been getting really, really creative with this. They'll stack parallel stents. I've even seen bare metal stents be used more frequently in these patients. We just repeat the ERCP until the stricture resolves. But after patients have had about four of them, I usually start to consider a biliary reconstruction. We can also see recurrence of primary liver disease. And the main ones are hep B, although we'll put them on lifelong hep B medication to ensure that that won't be a problem. Recurrent NASH is a big one that can recur quite quickly in the allograft. Primary sclerosine cholangitis can recur, as can primary biliary cholangitis. And I want to keep the PBC patients on ursodiol to really slow that reoccurrence. And then autoimmune hepatitis can actually reoccur as alloimmune hepatitis post-transplant. And this is actually histologically different than rejection. So they usually require a little bit more immunosuppression. The liver, by and large, is a very immune-tolerant organ. So we can usually have these patients on monotherapy with immunosuppression, but these alloimmune hepatitis patients may require a little bit more. Infection obviously can be a problem in any immunosuppressed patient, not just transplant patients, as well as the complications of really long-term use immunosuppressants, which can be renal insufficiency, metabolic syndrome, gout, bone disease, meaning decreased bone density. We think of little old ladies who are 90 pounds soaking wet as the ones to get osteoporosis, but a lot of times liver transplant patients will get it as well. So even if it doesn't necessarily make its way into the USPSTF guidelines for that patient, you may want to consider a DEXA scan to rule that out. And then lastly, malignancy, because we lower their immune system enough that their body doesn't fight their organ, but sometimes it's lowered enough that it's not fighting off cancers either. So what does the follow-up look like? Transplant centers usually follow the patient very, very closely for that first year, because that's usually when most liver-related complications occur. They'll oftentimes be looped in and continue to manage any sort of hepatobiliary complication, like the rejection, stricture, or any recurrent liver disease. But long-term management may fall to the community provider, whether that be a PCP or a GI, and one of the take homes is that the blood work, when you draw a level for the immunosuppression, needs to be a true trough. So for example, if they take their tacrolimus at nine in the morning and nine at night, that blood needs to be drawn between 8.30 and 9 a.m. before they take that morning dose, because that's the level that clinicians will titrate off of to change their immunosuppression. Now, I recommend that any modifications to immunosuppressants should be done in close collaboration with the transplant team. It may also be beneficial to contact them if you wanna start any sort of new medications or supplements in these patients to make sure it doesn't affect the progress levels, making them either too high or too low. And I do say tacrolimus, because that's one of the most common, but cyclosporine and the other immunosuppressants as well. And here I've outlined them. I know we're not supposed to include brand names on these talks, but a lot of times brand names are all the patient's knows, and each drug has lots of different names, as you can see. The CNIs, tacrolimus can also be called FK506 or Prograf, cyclosporine will be abbreviated to CSA, and then there's Neoral or Sandimune preparations. And I wanna let you know that these are modified and non-modified, and if you're refilling these scripts, these two are not interchangeable, so it's very important to pay attention to the type that the patient is on. The mTOR inhibitors, they're usually not used in the first 30 days post-transplant due to the increased risk of hepatic artery thrombosis, but these are serolimus or rapamycin, also known as rapamune or everolimus, which is often abbreviated as EBR. We also have mycophenolate, that's abbreviated to MMF a lot of times. These are also called Celcept or another brand name is Mifortic. And if this patient's on Mifortic, it's usually because their bellies got upset with the Celcept, so they were switched. And then azathioprine or AZA, also known as Imuran. There's the glucocorticoids, prednisone is the one that's most commonly used, although I haven't seen an increased use of budesonide even with those alloimmune hepatitis patients. So the diet after liver transplant, it's really important for these patients to avoid grapefruit and pomegranate because it directly impacts the metabolism of the immunosuppressants. These patients wanna avoid raw or undercooked meats, unpasteurized cheeses, things like that. Herbal supplements are generally a no-no in liver transplant patients, but specifically the ones I have listed here, super important to be hydrated after transplant due to the methotoxic drugs that the patient is on. And just good measure for all of us, low-salt, low-fat diet, because they do have a predisposition to cardiovascular disease long-term. Patients may also need a low potassium diet because tacrolimus can make them hyperkalemic and they may need extra calcium and vitamin D due to their risk of osteoporosis. And of course, since it's a liver transplant, you wanna advise them to avoid alcohol, especially if that was their underlying liver disease. So equally importantly is mitigating cardiovascular risk as far as preventative care. Screen for hyperlipidemia and treat with statins if you need to. These are okay. There's an urban legend that liver transplant patients can't be on statin, but that couldn't be farther from the truth. Pravastatin is preferred, but I sympathize with clinicians starting it because it's like water. So if needed, atorvastatin is fine. You wanna avoid cholestyramine, however. Not only does it not offer the anti-inflammatory benefits of a statin, it can actually impair the absorption of CNIs. As far as the diabetes, sometimes they're on insulin early post-transplant. That's called post-transplant diabetes mellitus. You may need to avoid metformin in these patients. Oftentimes we steer clinicians toward glipizide post-transplant. Hypertension needs to be aggressively managed with beta blockers or calcium channel blockers. We wanna avoid ACEs and ARBs in these patients due to the risk of hyperkalemia with the tacrolimus. And diuretics are usually not used as a primary therapy for hypertension because their kidneys are already under enough stress. As far as mitigating renal disease, the cause of renal disease post-transplant is multifactorial. These patients have had insult after insult on their kidneys. Oftentimes they have preexisting chronic kidney disease or they've had hepatorenal syndrome. They can experience acute tubular necrosis during the liver transplant itself. And then afterward, we put them on very nephrotoxic drugs that predispose them to diabetes and hypertension, which we know just wreck the kidneys over time. So how do we mitigate this? We run them at the lowest possible CNI level once their maintenance immunosuppression has stabilized. We wanna aggressively control the diabetes and the hypertension, avoid other nephrotoxic drugs, especially NSAIDs. Another rumor that I'd like to clear up is that liver transplant patients can't be on acetaminophen. They can. It's actually much better for them than the NSAIDs, but you do wanna limit it to two grams daily, which is half of what's on the bottle. It's still a lot of Tylenol. That's still four extra strength Tylenol in a 24-hour period. As far as infection, we are all painfully aware of how to prevent infection these days, but transplant patients have basically always been following COVID precautions, doing hand-washing, masking, avoiding public places. But some things I really wanna draw your attention to is that they shouldn't consume river or lake water. They wanna avoid high-risk pets, such as birds, rodents, snakes, chickens, things like that. Use precautions against ticks and mosquitoes. And any sort of travel plan they need to review with their provider. And I always advise my patients to put their immunosuppressants in two places, whether it's the carry-on in the checked bag, their wife's purse, and their carry-on, just in case something happens to one of the bags. Opportunistic infections are huge post-transplant. This is sometimes a weak area for community providers. Cytomegalovirus is one of the biggest issues. It's most common very early on in the post-transplant period, especially within the first four months, when there is a positive donor liver going into a body that is naive to CMV. That's the highest risk, and we call that a CMV mismatch. If patients develop a CMV viremia, they can complain of headaches, fever, fatigue, myalgias, and cytopenias, which can also be caused by a lot of the drugs these patients are on. But sometimes they also have bad GI symptoms, such as nausea and diarrhea. We wanna treat this aggressively. We usually use valgancyclovir. There are other treatments, especially IV, available, but we want to prevent any sort of end organ issues, such as CMV colitis, pneumonitis, hepatitis, nephritis. And I've actually had patients go blind because of CMV retinitis. Epstein-Barr, another virus that can cause some issues, that's the monovirus. But post-transplant, it can predispose patients to post-transplant lymphoproliferative disease, or PTLD, a very rare lymphoma that only transplant patients get. And how they present is usually night sweats and weight loss. Occasionally, they'll have a palpable node. And the treatment for this is minimizing the immunosuppression and even getting them off of it, if possible. Sometimes they are candidates for CHOP, sometimes not. It depends. And then we also prophylaxe against PJP pneumonia with Bactrim, but Bactrim can oftentimes also cause hyperkalemia, as well as an elevated serum creatinine, two of these things that we're already trying to avoid. If necessary, these patients can be switched to Dapsone. Post-transplant malignancies. I always tell my patients, absolutely no smoking. You will 100% get a cancer. And with that being said, we need to really be more intensive about screening patients. Skin cancer is the most common malignancy post-transplant. It's usually squamous cell or basal cell carcinoma. Sometimes you can switch these patients from a CNI to serolimus, but I just really push frequent full body skin exam screenings with the dermatologist. Because if you get these removed, they're no big deal. It's very rare that I see a melanoma across my desk. We already talked about PTLD. If your patient has PSC and ulcerative colitis, you really want to make sure they're staying on top of their colon cancer screenings, any sort of recurrent viral hepatitis, such as hepatitis B. You want to make sure you're screening for hepatocellular carcinoma. And the patients who are transplanted for ALD are more at risk for the oropharyngeal and esophageal squamous cell carcinomas. As far as vaccines, patients may lose immunity during the transplant process. And it's common to wait three to 12 months post-transplant to make sure that the vaccine takes. Flu can actually be given up to as early as one month post, same with COVID-19 vaccine. Although I do like to wait if my patient has received an induction in the OR. And as we all know, these patients can now get a third dose of the COVID-19 vaccine. High dose vaccines, like the high test hepatitis B vaccine, they help these patients develop more robust immunity. These patients need yearly influenza vaccines. They need both pneumococcal vaccines, even if they don't meet the age, even if they're young, they need these. I suggest no live vaccines ever. They can get the new shingles vaccine, not the old one. I also recommend that household and close contacts need to also be vaccinated. I don't recommend that children not get their MMR and live virus vaccines, just because they're living with a transplant patient. I do tell them, the transplant patients, to try to avoid diaper changes if possible, because these children will shed it in their stool. But sometimes life is life and you need to change a baby's diaper, in which case mask, gloves, major, major hand-washing and good hygiene. Lastly, pregnancy and reproduction. Women often experience amenorrhea, but fertility does usually return after transplantation. We want to avoid the use of teratogenic immunosuppression in patients of childbearing age. If they cannot be avoided, you wanna educate the woman to use not one, but two forms of reliable contraception. One in four of children born to women that were on MMF will have a birth defect and about half of the pregnancies ended in miscarriage. So you may want to switch the mycophenolate to azathioprine if your patient is even thinking about becoming pregnant and loop in a high-risk OB. As far as male sexual dysfunction, cladonafil is okay, and I know that's super important to our patients. So the key takeaways I have for you, the two liver complications, you'll likely see your rejection and stricture, so watch out for them both. Blood work needs a true trough level of the immunosuppressant. Ascites and elevated LFTs are never normal post-transplant and always warrant for their follow-up. Mycophenolate is bad in pregnancy. You need to have a low threshold of screen for cancer and treat infection. You need to do everything you can to mitigate cardiovascular and renal disease. Don't forget a DEXA scan and always collaborate with the transplant center for all immunosuppressant changes. Thank you. Hello there. Today, we're gonna be talking about opportunistic infections and end-stage liver disease. My name is Leah Turner. I'm a nurse practitioner at the Hospital of the University of Pennsylvania, and my primary focus is transplant-related infectious diseases. I am the co-course director for the Penn Medicine Infectious Diseases Advanced Practice Provider Fellowship. You're also gonna be hearing from Chelsea Sammons, who is a clinical pharmacy specialist at the Hospital of the University of Pennsylvania, and she primarily covers liver and vascular composite allograft transplant. She's also the residency program director of the PGY-2 Solid Organ Transplant Pharmacy Residency. We have no disclosures to report. So today, we're gonna be talking about the epidemiology of opportunistic infections and end-stage liver disease, prevalence and risk factors for multidrug-resistant organism infections, and antimicrobial pharmacologic issues in cirrhosis. We're gonna start with a case presentation that we will come back to through the course of the presentation. Mary is a 49-year-old female with a history of stage III chronic kidney disease and decompensated NASH cirrhosis, complicated by ascites, who presents to your emergency department with fevers, abdominal distension, and abdominal pain. She undergoes a large-volume paracentesis and is started on empiric IV ceftriaxone due to concern of spontaneous bacterial peritonitis. So keep this in mind as we continue the presentation today. So we're gonna start with epidemiology. Bacterial infections are a frequent complication in patients with cirrhosis, present in 32 to 40% of patients. They cause for significant morbidity and mortality with mortality rates as high as 30 to 50%. Infections are the leading cause of acute decompensation and can oftentimes precipitate other decompensations such as variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. They can be major precipitants of acute on chronic liver failure. We know that patients with end-stage liver disease have an impairment in their immune systems, increasing their susceptibility to infections. This impairment contributes to high incidence of infections and mortality rates in these patients. Cirrhosis-associated immune dysfunction incorporates both immunodeficiency and systemic inflammation that occurs in cirrhosis. Immunodeficiency results from damage to the local immune surveillance function of the liver and reduced hepatic synthesis of proteins that are involved in innate immunity and pattern recognition. Additionally, intestinal mucosal alterations and decreased bacterial clearance can predispose these patients to bacterial translocation. Systemic inflammation is reflected by pro-inflammatory cytokines, which may contribute to other complications such as renal impairment and increased mortality. All of these factors contribute to an impaired susceptibility to infections. Risk factors associated with infection in these patients include severe liver failure, variceal bleeding, low protein ascites, and prior episodes of spontaneous bacterial peritonitis, which predispose patients for future episodes of SVP. The most common infections we see in patients with end-stage liver disease are spontaneous bacterial peritonitis, spontaneous bacterial peritonitis, which accounts for 20 to 35% of all infections and frequently precipitates acute kidney injury and acute on chronic liver failure. Urinary tract infections, which account for 14 to 41% of infections. Pneumonia, which accounts for 8 to 17% of infections. Bloodstream infections, accounting for 8 to 21% of infections. And skin and soft tissue infections, accounting for 6 to 13% of infections. Spontaneous bacterial peritonitis is the most frequent infectious complication in cirrhosis, with the incidence in hospitalized patients with cirrhosis ranging from seven all the way up to 25%. Short-term mortality, defined as death within 30 days of diagnosis, is high, with rates ranging from 15 to 40%. Clinical trials comparing treatment regimens are somewhat limited, but in practice, the most commonly used treatment is a third-generation cephalosporin. And we will talk about why this is potentially becoming more problematic in a few slides. Prophylaxis is indicated for patients with a history of upper GI bleeding, low protein ascites, and prior SVP, but data are not well substantiated. The most commonly used regimens tend to be trimethoprim, sulfamethoxazole, or an oral fluoroquinolone. A 2020 Cochrane review found considerable uncertainty about whether antimicrobial prophylaxis is beneficial and which antibiotic prophylaxis is most beneficial. Future randomized controlled trials are needed. Urinary tract infections are a frequent complication in patients with end-stage liver disease, with a higher incidence in men than women. Incomplete bladder emptying due to ascites is a possible mechanism, and there is a positive association between women with primary biliary cirrhosis and urinary tract infections. The next slide is a little bit more complicated. Urinary tract infections are a frequent complication in patients with advanced liver disease. Pneumonia is seen in about 21% of patients with advanced liver disease, but the mortality rate as high as 41%. Hepatic encephalopathy and procedures such as intubation can predispose patients to pneumonia. These patients are at higher risk of both community and healthcare-associated pneumonia. Of course, pneumococcal vaccination is extremely important in this patient population. Pneumonia can be a serious infection in patients with cirrhosis, and may be a spontaneous or sequelae of infections at other sites like bladder, lung, or skin. It may also be associated with therapeutic invasive procedures. Other infections can be seen in end-stage liver disease, such as skin and soft tissue infections, fungal infections, and viral infections, such as influenza, and more recently, SARS-CoV-2. So some of the key takeaways. Infections are common complications in end-stage liver disease. Impairment in immune system regulation and cirrhosis contributes to this. SBP is the most common infection, but other infections include urinary tract infections, skin and soft tissue infections, pneumonia, and bloodstream infections. So now we're gonna talk about multidrug-resistant organism infections. Globally, the overuse of antimicrobials and failure of control measures to prevent the spread of multidrug-resistant organisms in healthcare settings has contributed to a growing problem. In patients with end-stage liver disease, repeated antibiotic exposure through prophylaxis or through therapeutics, including third-generation cephalosporins, fluoroquinolones, and beta-lactams, have contributed to the growth of these infections. Frequent exposure to the healthcare environment and invasive procedures are also risk factors. Unfortunately, the efficacy of classically used third-generation cephalosporins has decreased over the past decade due to the emergence of multidrug-resistant bacteria. Infections caused by multidrug-resistant organisms are associated with higher mortality, increased length of hospitalization stay, and more cost to the healthcare system. So we're going to talk about a review of a multicenter study in Europe that looked at multidrug-resistant bacterial infections in patients with end-stage liver disease. This was the largest multicenter study to date with a prospective evaluation of two series of patients hospitalized with decompensated cirrhosis. The first series included about 1,100 patients from Northern, Southern, and Western Europe in 2011. The second series included 883 patients from Eastern, Southern, and Western Europe investigated from 2017 to 2018. This study evaluated the epidemiology, clinical characteristics of bacterial infections, and empirical antimicrobial choices in these patients. In the first series in 2011, 40% of the patients developed infections with SBP, UTI, and other pathogenic infections. UTI and pneumonia being most common. Of the culture-positive infections, close to 30% were caused by multidrug-resistant organisms. Extended-spectrum beta-lactamase-producing Enterobacteriaceae was the most frequent. In the second series in 2017 to 2018, the prevalence of multidrug-resistant organisms in culture-positive infections increased to 38%. Nosocomial infection, intensive care unit admissions, and recent hospitalization were identified as independent predictors of MDR infection. So returning to our case of Mary, her culture data returns from her paracentesis and demonstrates an ESBLE coli. As you can see, this isolate is resistant to ceftriaxone. In light of this, her ceftriaxone is switched to erdapenem for a planned seven-day course. Early diagnosis and choosing appropriate antimicrobials are incredibly important in the management of these infections, and delays in appropriate antimicrobials can contribute to poor outcomes. Key takeaways. Multidrug-resistant bacterial infections are prevalent and growing healthcare problem in patients with decompensated cirrhosis. Antibiotic resistance is associated with worse prognosis and higher mortality. And early diagnosis and correct antimicrobial choices are key to management. The remainder of this presentation will focus on antimicrobial pharmacologic issues in cirrhosis. Renal dysfunction is very common in patients with cirrhosis and is more likely seen in patients who have developed ascites. Pathophysiologic changes such as systemic vasodilation and decreased SVR lead to changes in circulation and subsequent decreased renal perfusion. There are many risk factors that lead to renal dysfunction, with the most common being hypovolemia. This could be related to diuretic use for ascites management, or blood loss due to GI bleed or variceal hemorrhage. Other risk factors include bacterial infections, especially SVP, as well as the development of hepatorenal syndrome. The severity of renal dysfunction and subsequent treatment ranges from AKI, which may be managed with volume to more severe situations that require renal replacement therapy. The degree of renal impairment, as well as the mode of treatment such as dialysis will impact the excretion of renally eliminated medications. Identifying the amount of renal clearance can be tricky, especially as renal function may change daily. Dosing medications appropriately can be a challenge in this population, as commonly used antibiotics rely heavily on renal function for elimination, such as penicillins, cephalosporins, carbapenems, and fluoroquinolones. One exception is ceftriaxone, which we do use commonly to treat SVP. Most institutions have resources available on how to appropriately adjust these medications for estimated creatinine clearance. But assessment of clearance in these patients is challenging. Also, keep in mind that creatinine clearance may overestimate renal function in this population due to reduced muscle mass. There is limited data available on how to renally adjust medications used for SVP prophylaxis. Below is a standard adjustment we use at our institution to help be consistent and decrease confusion. The severity of hepatic dysfunction and its consequent effects on drug dosing is even more difficult to quantify than renal dysfunction. The liver is involved in various stages of pharmacokinetics, including drug distribution, metabolism and excretion. Alterations in these functions leads to variable effects on drug levels. However, antibiotics rarely require hepatic dose adjustment for a few reasons. The liver is remarkably resilient, and its metabolic capacity needs to be reduced by greater than 90% before drug metabolism is appreciably reduced. In certain situations, our body may compensate for reduced liver elimination by increasing renal elimination. And overall, these drugs have a wide therapeutic range, which means marginal increases or decreases in drug levels do not affect the degree of safety and efficacy. Like I mentioned earlier, most antibiotics we commonly use in this population are renally eliminated and would not require hepatic dose adjustment. However, you should use extreme caution with combined end organ dysfunction. Not a focus of this presentation, but a few antifungals require hepatic dose adjustment, including voriconazole and caspofungin. There are also dose adjustments for severe hepatic impairment for ticacycline and metronidazole. Overall, it's important to consider multiple factors before adjusting medication doses and end organ dysfunction. Indication such as treatment versus prophylaxis, severity of infection, and clinical stability of your patient will have implications for how aggressive your antibiotic dose should be. For example, treating a bacteremia in an ICU patient warrants more aggressive dosing and SPP prophylaxis for a four patient. The duration of therapy and the capacity to allow drug to accumulate over time is another factor that needs to be assessed. And finally, the degree of end organ impairment, if it's acute or chronic in nature, as well as the pharmacokinetics of the antibiotic regimen will help guide the decision on whether a dose should be adjusted. Now we can apply these concepts back to our case. To refresh your memory, Mary is on erdapenem 1 gram 224 times seven days for SPP treatment. Three days into her treatment, her serum creatinine starts to rise. And you can see this trend in the table below. Her creatinine clearance on day five of treatment is 28.9 mils per minute, which is slightly below the creatinine clearance cutoff to renally adjust erdapenem. Thinking about whether your medications are dosed appropriately in this scenario is warranted. Some may jump to decrease the erdapenem dose based on the creatinine clearance number being less than 30. But let's think through these factors. This is treatment of a site that can be difficult to penetrate, and there are only two days left of therapy. Additionally, her serum creatinine seems to be plateauing. This AKI could be a result of volume shifts, even the recent LVP. So my instinct was to continue the current dose. We're also going to discuss drug-induced hepatotoxicity. This type of toxicity is overall rare with an annual incidence of three to 14 cases per 100,000 patients. In general, patients with liver diseases are not at an increased risk for hepatic injury, but are more likely to have complications from this injury, including decompensation. Antibiotics represent a third of all cases. And these reactions are mostly idiosyncratic, so not linked to a certain dose or duration, but largely unpredictable. Drug-induced hepatotoxicity can be difficult to diagnose, as signs and symptoms may not be apparent for weeks after the offending agent has been discontinued. This may be related to toxic metabolites that may persist in the body long after the parent compound is gone. The type of injury could be mostly hepatocellular or cholestatic or mixed, and the severity ranges widely from self-limiting despite drug continuation to acute liver failure. Some reactions can be accompanied by other symptoms such as fever, rash, eosinophilia, or GI distress, and reactions may worsen on repeat exposures. Given the rarity of drug-induced hepatotoxicity, and the severity of infections and end-stage liver disease, potential causative agents should not be avoided. However, use extreme caution in severe hepatic impairment. Being aware of possible causal agents is crucial to facilitate timely intervention, as most patients recover if offending agents are withdrawn quickly. Given many antibiotics known to cause drug-induced liver injury are used commonly in serotics, vigilant monitoring is key. Pay particular attention when using amoxicillin clavulanate, sulfamethoxyltrimethoprim, and fluoroquinolones. In summary, hepatic and renal impairment affects pharmacokinetics, leading to possible need for dose adjustments. Talk to your pharmacist if you are ever unsure about dosing antibiotics in your serotic patients, especially when renal function is also compromised. Although rare, antibiotics are common causes of drug-induced liver injury. Vigilant monitoring and awareness of likely causes is critical for quick intervention. I want to thank all of you for listening. I hope you enjoy the rest of the conference. Hello there. Thanks for joining me for this talk as part of the Hepatology Associates course at the AASLD meeting. The title of my talk is End-Stage Liver Disease at and I've added in before the end of life. My name is Victor J. Navarro. I'm Paul J. Johnson, Chair for the Department of Medicine at the Einstein Healthcare Network and Professor of Medicine at the Sydney Common Medical College in Philadelphia, Pennsylvania. I am funded by the Patient-Centered Outcomes Research Institute to conduct research which is discussed very briefly in this presentation, but I have no other commercial relationships. I'm going to touch on three topics today. We'll talk about the growing burden of liver disease, understanding and communicating trajectory of disease, and end up with the principles of palliative care and how to incorporate them into your practice. First of all, the trends of chronic liver disease are quite striking. I'm not showing you the overall increasing prevalence of liver disease, which exists, but what I'm showing you here is from a publication in 2018, where the investigators looked at the severity of liver disease in hospitalized populations. And what we were finding as you see in the solid line, and also the small dotted line, is that patients with severe illness were ending up in hospitals with increased frequency compared to those with less severe illness. So overall, there's an increasing trend of liver disease or increasing burden of liver disease in the population, and patients are becoming more ill when they arrive and are taken care of in the hospital. Now, let's talk about understanding and communicating the trajectory of disease. If we look at what we know from now a very long time, the outcomes in end-stage liver disease are pretty well known. If we look at the outcomes and stratify them according to the severity of illness, it gives us an idea of what we should understand and be telling patients. The very mild cirrhotic, those perhaps patients who have not sustained complications at Child's Pew A, as you can see here, has a one-year survival and two-year survival, that's quite good. But as the patient decompensates, becomes Child's Pew B or C, that one and two-year survival falls dramatically, as you can see. And of course, nowadays, we use the MELD score. And that MELD score is tied to the three-month patient mortality. And that too, is a very useful way to gauge a patient's predicted outcome. But survival, mortality, those aren't the only important factors that we should understand and explain to the patient as we take care of them. Rather, we have to understand that there are other measures of impact of the impact of end-stage liver disease. They include the symptoms, the quality of life, depression and distress, and an often overlooked burden on the caregivers, as well as finances and employment. Symptomatology among patients with chronic liver disease is pretty heavily impacted. Now, I adapted this from a 2019 paper. But if you look at patients who have end-stage liver disease, which is the leftward or the leftmost kind of aqua green bar, you can see that for all domains, pain, insomnia, fatigue, depression, and anxiety, patients who have end-stage liver disease really are very similar to those with other life, you know, life-limiting or really health impacting diseases, cancer, heart failure, and end-stage renal disease. Now, as regards communicating the trajectory of disease, we've got to keep in mind, not only the survivorship, but also the symptoms, the complications of disease, which are beyond the scope of this talk, but you know them well, being hepatology providers. But we have to discuss those things with the patient early in the relationship. And not only with the patient, but also the family, we have to revisit this discussion on with each encounter. Oops, sorry. And that becomes very, very important. And finally, we have to acknowledge the patient's caregiver and the burden placed upon them. Now, I want to take that important factor, comment and notion of communicating the trajectory of disease as well as an understanding of the disease process, and incorporate that into the principles of palliative care. Now, this is very important, because I think people have some misconceptions about palliative care. But you and I as hepatology providers really all engage in basic palliative care. And this really means that specialists like you and I talk about the disease trajectory and potential outcomes. So it's very disease oriented. We don't have special training in palliative care, but it's part of what we do. Now, that's a bit different from end-of-life care, where we're really addressing the global needs of a patient who's got severe illness, whether they be medical, social, emotional, and spiritual. Different is hospice care, which is kind of the treatment that we would give patients with limited life expectancy. There are often insurance benefits to support hospice, and usually patients have fewer than six months to live. And our focus is on comfort, as well as on the caregivers. Palliative care is kind of the broader term applied when we're treating pain, symptom relief, quality of life. The important thing about palliative care as an umbrella term is that this really could be thought of as something that we should engage in early. So palliative care really is an excellent way to look at treating our patients with the idea of symptom management, outcomes, and communicating this over the time of their disease. Finally, specialty palliative care is that which is rendered by board certified palliative care doctors. They work in many different settings. Unfortunately, there really is a paucity of palliative care specialists in American medicine today. But however it's rendered, there are certain principles of palliative care, which are crucial for all of us to understand. We already talked about understanding disease process and prognosis and how important that is to communicate that to families. It's our understanding of the disease is how we manage these patients on a day-to-day basis, as well as manage their symptoms. Communicating those disease outcomes and symptoms to patients so that we can treat them fully and engage patients is really, really important, as well as discussing what these symptoms mean and how they should be treated in collaboration with the patient and the family, so-called shared decision making. But we also understand that palliative care includes advanced care planning and advanced directives, as well as caregiver and bereavement support. I'm going to focus for a second on advanced care planning, because this is a certain vernacular which we should all understand. Advanced care planning includes discussions of goals of care, end-of-life care, what a patient wants when there truly is no other curative or life-sustaining treatments available. What are their preferences, goals, priorities, and they also should be documented and in fact, be flexible because some patients may change how they see life and the end of life. Advanced directives means that they have identified a healthcare agent, someone to make decisions for them if they become unable, identify a living will or fill out a living will, and also identify the durable power of attorney. Palliative care specialists do this routinely, but we as hepatologists, if we're going to provide basic palliative care should also be able to address these things. Now palliative care, which I hope I'm rendering to you as a concept and an approach that could be given to patients and considered early in disease trajectory because it is not just hospice or end-of-life care. But the outcomes are important for us to understand why is it important? Well, these three bullets, I hope give you an idea of why palliative care, even at its most basic form that you and I routinely administer to patients is so valuable. First of all, patients who engage with their providers and palliative care, some of those things we discussed are less likely to be admitted to the ICU or ER, and they have improved patient reported outcomes or pros. Their symptoms are better, they have less depression, less distress, which can be measured, the quality of life improves, which can also be measured, and they actually have an improved satisfaction with care. They're also very well documented reduction in the costs of care. Now, one of the most, I think, important studies in palliative care to show the heart impact and the benefit was in metastatic lung cancer, published by Jennifer Temel and her group in a single center study in 2010, in the Harvard system. And what they showed is that patients with advanced metastatic lung cancer actually had an improved survival when they received early palliative care. So this study really opened our eyes to other patients who have life limiting chronic illnesses that palliative care really does have a benefit. And it goes, of course, beyond survival to many of the other things that I just listed for you. Now, what about liver disease? Well, palliative care access has improved for hospitalized patients as shown in this study with end-stage liver disease. And this group showed that over time, there was an increase in the use or consultation for palliative care. What I'm not showing you here is although this has continued and probably continues on today with an increasing rate of palliative care consult and utilization, there still are some disparities that go beyond this graph and touch on things such as socioeconomic barriers, and educational barriers that limit access to palliative care. And there was a very important study I want to highlight to you, done a few years ago in the UK, where they did a purpose of sampling of physicians and patients, mostly physicians, I think exclusively physicians and found with this mixed methods, how do specialists really regard palliative care? Well, what was found is truly patients with end-stage liver disease have a high symptom burden. But what was alarming about the study is they showed us that clinicians rarely discuss prognosis, they lack the skills and confidence to discuss prognosis, and palliative care was poorly understood and frankly, negatively perceived by providers. So one of the things that I want this audience to be aware of, which gives you a wonderful step-by-step approach to palliative care management early in the trajectory of disease all the way through the continuum to hospice care and end-of-life is this AGA clinical practice update on palliative care management in cirrhosis. This is a wonderful overview, it's concise, and it gives you 10 points of best practice advice, many of which I've touched on in this article, but it's laid out beautifully for the practicing clinician. And it also points out some of the common misperceptions that exist out there, specifically that palliative care is equated with hospice care, and it's not. Hospice care is one component of palliative care. That palliative care is inconsistent with curative treatment, it's not. The two are not mutually exclusive. In fact, palliative care offers much benefit in symptom management, in caregiver burden relief, in patients who are awaiting transplant. So they can be given and benefit from palliative care, even if they're looking for transplant. And finally, another misconception is that palliative care is just for the decompensated cirrhotic, and it is not. It should be discussed early in the disease trajectory, similar to what was the case for patients with metastatic lung cancer. We know that improved outcomes. Now, how convinced are we that palliative care can benefit our patients with end-stage disease? We're so convinced that there's now a large study that has been funded by the Patient-Centered Outcomes Research Institute called the PALOVER study. The PALOVER study is ongoing, and it's entitled Introducing Palliative Care Within the Treatment of End-Stage Liver Disease, a Randomized Controlled Trial. And what we're doing in this study is looking for a new model that is driven by hepatologists to render palliative care early, not just hepatology physicians, but also advanced practice clinicians. And we feel that if we can train hepatologists and advanced practice clinicians, the principles of palliative care and palliative care delivery, that we can improve the quality of life. There's now 17 sites around the country. We're in our third, fourth year of the study, and we really are eager to see that we're going to show that we, hepatology providers, can really have a positive impact on our patients with end-stage liver disease if we start early in the disease trajectory. So let me summarize with these key takeaways. The burden of chronic liver disease, I should say the burden of severe chronic liver disease, is increasing. The provider must understand and communicate the trajectory of disease. That includes not only the outcomes, but the symptoms and the complications. And this should be, as pointed out in the AGA guidance, discussed at just about every, what they call, sentinel event, whenever there's a complication. And frankly, I touch on this whenever I have an office visit with the patient, to be sure they understand what the symptoms are and potential outcomes. We should assess caregiver support and burden, and all hepatology providers should be familiar with palliative care principles, as we discussed in this talk. And finally, early palliative care has beneficial effects. It's shown in lung cancer. We know that it exists, the benefit exists in liver disease, and we'll show it through our study. A timely hospice referral is appropriate, when survival is expected to be less than six months. I wanna thank you for your attention, and I wish you the best of luck in your practice, and I hope you enjoy the meeting. Thank you very much. Hi, I'm Chirag Desai. I'm one of the transplant surgeons at University of North Carolina. I do the liver and the other abdominal organ transplantation. I'm here today with Mr. Cockrell, whom I will give him an opportunity to introduce himself. Mr. Cockrell received a liver transplant in April of 2020, and this program is about the hepatology associate course, with the title is, My Story Shared by a Patient and a Transplant Surgeon. So we are going to have an interactive session with Mr. Cockrell, explaining his experience around the transplant, and the expectation and deliverance about it. So first, to go over it, I'll let Mr. Cockrell introduce himself. Mr. Cockrell, welcome. Thank you, Dr. Desai. My name is Larry Cockrell. I live in Big Waverly, North Carolina. I've been married for 34 years. I have five children, ages 23 to 29, and I'm 18 months post-liver kidney transplant. That's great, Mr. Cockrell. And we both of us are thankful to AASLD and Hepatology Associate Course for inviting us here. So Mr. Cockrell, let's start with your preoperative stage, when the first time you were diagnosed with the liver disease, and then you were told that you would require a liver transplant, and you walk us through your evaluation process, and then first time meeting your surgeon and the transplant team, and you understanding and getting a confidence about this team. And then I'll explain what, from my perspective, a similar thing. Well, before I was diagnosed, I knew I was sick, and I was pretty confident I knew what the problem was, but it really hit home when I was actually diagnosed by my physician and telling me I was gonna need a liver transplant. And of course, that's scary. You know, you just don't get a liver from anybody. You just don't pull one off the shelves at the store. So, you know, I met with you, Dr. Desai, and I felt a lot more confident with how things were going, between you and the transplant team and everybody else I talked to at UNC. It helped relieve a lot of worries. But by the time I got to the hospital, actually, I was inpatient when I received the news about the donors and moving forward. I'd already been in the hospital three times for the emergency room visits, spending four to five days in a step-down unit due to issues leading up to that. I had 24 paracentesis procedures. I was retaining a lot of fluid with my ascites. So by the time I got to the hospital, I was ready to move forward. So from a surgeon's perspective, when we meet the patients, you know, I'm not going to go in the details of the medical evaluation because this crowd knows a lot about it. But I think from a surgical point of view, what I wanted to know is like, either it's outpatient or inpatient evaluation. It does make a lot of difference because in outpatient evaluation, many of these patients are suffering for many years and they are prepared by the hepatologist and they come for a transplant with a little more understanding. But when we do the inpatient evaluation for sick patients like you, we had a very short time to establish that rapport. The most important thing is to have that development of trust in each other, that you feel that I could take a good care of you and I feel that you will take a good care of the liver we put in and yourself. And understanding and explaining this is the key process. And we were lucky in your case because I think you have two daughters who are like nurses and your wife is also a nurse. So it was a very smooth process explaining this because, you know, transplants are very well orchestrated now, but when the complication happens, it's 100% for you, whatever the percentage we give it in the literature and all. And that's where the patients, if they are not understood this process well, then the problem comes. So I must say that my experience with yours was a little easier than the most others, but that's the key when we want to evaluate these patients over and about the surgical evaluation to make sure that we are getting a message across right. Now let's talk about your surgery day. You know, like describe your feeling when you get a first phone call that, oh, you are getting a liver now and what did you think of meeting your team at that time? Because a lot of new people you will meet, you know, residents, fellows and all, and your comfort and confidence and relief based on what you have thought about this experience and any particular memory of this, which you want to share with us during that time of the transplant. Well, by the time that came around, I was ready. I mean, I was more scared of continuing to live the way I was living. I was building the sinus fluid, not building, retaining fluid at a rate of about a liter to a liter a quarter a day. So mentally and physically, by the time this came around, I was ready. And my kids asked me, dad, are you scared? I said, look, it is what it is. My faith is going to be in Dr. Tsai, UNC transplant team and God. So, excuse me. So whatever he has plans for, that's all there is to it. You know, I just, I'm scared of continuing to go in the way we're going. So no, I was ready. And when they came in, but I was scared too, because, you know, COVID was just starting to come around at this time. Was I going to be eligible? Because I need the kidney also. So there was a lot of unknowns there. But I wasn't as scared as what I guess a lot of people might be. I was just ready to go. So when I was told that they found the donor for the liver and the kidney, I was like, wow, this is going to, we're getting somewhere. And then after everybody left the room, I got to thinking, oh, excuse me. Somebody's got to die for me to move forward. So, so that was tough. But, you know, you get through that and then you say a lot of prayers and you just keep on plugging away and keeping faith in the transplant team. And everybody was great at UNC. And just faith that there was a plan for me moving forward. Sorry for the motions. No, that's only human. That's a threat actually. Because, you know, many times we see a lot of patients and we as a transplant surgeon know from both sides that we, our team goes for a procuring. I myself have done a lot of procurements and then you put the liver in. So we see both sides. One is like a sad side where the liver is coming out from and the other is happier side where the liver is going in. But like sometimes some of the patients who are getting a liver transplant, they say inappropriate things and do not appreciate the other side's difficulty. So your emotion is really actually appreciative to me because that means you understand difficulties on the other side. For us, like from my experience going as a transplant surgeon going to go in a transplant is like, you know, a lot of phone calls starts coming first of all, like starting from the offer, from the donor place. Sometimes the donor keeps on getting delayed. And then we get getting these phone calls about how the liver looks, their biopsy and all that. And I had a chance to meet your whole family that day. I really remember, you know, everybody was there on the fourth floor room and explaining everything. And I joke around with all the patients but tell them this is serious, that, you know, you may not see me again after I explain everything but I'll be the one who will be doing transplant. So if your family, when the patient goes in the room and they take around two hours to put the lines sometimes, so don't get worried if you see me in the corridor doing some taking care of the other things. But as you said, your family was very nice and I had. And the most important thing for me is like, as you say that God had a plan for you, even the God has a plan for me. And I always say that, you know, like, I thank God for every opportunity I get to do this and live it. So even though I have done a lot of transplant, yours is a first for me. And it's my job to make sure that me and my team put all 100% in you and don't take it as a number, like say 100, 400, 500 transplant. And that's a good goal for us. Your transplant was a little challenging, you know, because you were pretty sick, you know, requiring tumor and kidney. And you had like that ascites, which was tapped at a hemorrhage before. So you had a hemorrhagic ascites, but I think we executed transplant very safely. It got over and then you were shifted in the ICU. I don't remember anything else other than just being a normal, tough liver transplant in your case. So once you went to the ICU, you know, you were like extubated in a couple of days. And I think you had a delayed death function of your kidney. Your liver worked right away and then you were on the dialysis also. So why don't you walk us through on your experience in ICU and then coming from ICU to the floor and how the, yeah, I think your liver had no problem, but your kidney functions had some struggle and then it come back to normal. So walk us through that experience now. So the surgery was on, transplant was on April 4th, Saturday evening, yeah. I didn't come out till June 4th. It was tough. I mean, like you said, the liver took fine. The kidney was an issue and I developed a hematoma. And I mean, there's a lot of things going on. I remember waking up after surgery and my left arm was bruised. It was black and blue. My right arm was not as severe, but it was discolored too, bruised up. And my skin on my arms and my neck, it was really fragile, like tissue paper. So, I mean, that was tough. And then fighting through that hematoma, I've had a kidney stone. That hematoma was right up there with the kidney stone, except the pain never subsided and that took a while. I remember telling one of my nurses one time, she asked me, how'd you sleep this weekend? Because she came back in on Monday and I said, I haven't, I haven't slept in two days because of the pain. I mean, I could tolerate it if I didn't move. Once I started moving, it was, oh, it was incredible. But I fought through that because when you're laying there at night and you can't sleep and a St. Jude's commercial comes on. And you see these kids that are sick with smile, excuse me, with smiles on their faces. You look to yourself and you say, hey, suck it up, big boy. Better get your big boy pants on and get moving because look at these kids right here and you're feeling sorry for yourself and you're wondering if it was worth it or whatever. You just, you need to make it worth it for your family and for your donor and for the doctors involved, Dr. DeSign, everybody else was involved. So that was tough, but I got through it and then I left ICU, went up to 7th floor with therapy and that was hard. When I went to the hospital, well, my normal weight was probably about 235 and I've gotten down to, by the time I left, about 165, 170. So, and I was weak because I was in bed rest for so long. So therapy was tough, but I looked forward to it. Once I started feeling confident with the physical therapist because they were tiny girls and I thought I still weighed 235 pounds and I didn't. But once I started feeling confident with them and the occupational therapist and everybody that's helped me get up and try to move and everything, it was great. I mean, I looked forward to therapy and it was tough. I mean, it was three hours a day, five days a week and sometimes they'd sneak in on Sunday and I thought that was my day of rest. But I was glad to see it. And I can't say enough for the people on ICU floor and in the therapy floor, from the nurses to the doctors checking on me and the doctors on the weekends and the residents and the CNAs that helped me a lot because I was taking some medications to help keep my potassium levels down. I mean, that was kind of tough. That's a hard part of this high-merit transplants. You know, when your merit score is so high, like around 40 to go into the dual organ transplant, the patient end up requiring going to the rehab. The seventh floor, what you're telling is a vacuum rehab where you had to go and do, you know, many transplant patients don't need to go and they recover much faster. And that's a challenge for us also because we want to make sure that, you know, you're back on your ground. So after all that, but as I can see you now, then you got discharged from rehab also. Then you go home and you started working and then tell us about your work, where you're working now and then how did you start working back and then your experience through a process and then we'll come to your one-year visit, you know? Well, when I came back, it was six weeks after I've gotten home and I probably came back a little too soon, but I was ready to do something. Once I was released to drive, I was ready to come back to work. Even if it was just four or five hours a day, I would come in, do nothing real physical, which I don't have a physical job anyway, for the most part. I'm a general manager for a brick manufacturing facility. So my job is administration and managing the plant. So I was able, I fortunately have good people around me that helped me out, but it was just good to get back and start to get into a routine. But by the time I got home, I was really tired. But it was just good to get back into starting a new routine anyway. And then I started getting stronger, stronger, stronger. And now I go to the gym five, six days a week. I'm there usually about 4.30 in the morning. And every time, every day I'm at the gym, I just look up and thank my donor. Hope I'm doing the right thing moving forward for them, because- That's excellent. I give a smile because five times a week at gym, then like, you know, that's my part to learn from you, I think. So, but yeah, I remember that, you know, like we have this like three months, six months, nine months and one year visit, and we have been watching you here and that. And then like Kim Jones was a coordinator and she did an excellent job with you. And the first year visit when you came and she pulled me, I was in a clinic and he says, hey, you want to meet Mr. Cockrell? And I just walked in. I couldn't imagine like, what's the difference between starting, right? You look like a different person. And then this opportunity came and we got connected and started talking. And then that's very satisfying to me because, you know, we see these patients for around a year, like hear about anything, something is happening to that patient, you know, like some complication or anything, but like people like you who are doing very well, we miss out the satisfaction of seeing you actually. And that this process actually, I thank Hepatology Associates, of course, that it gave me this opportunity to connect you with your team. It's my minor way of giving back. I've been after Kim Jones for a while to try to get me to do something because I wanted to be a transplant mentor. I've already been vetted to be a volunteer transplant mentor for UNC, but there's not a program right now. It's inactive. So this was just my way of giving back for me and my donor and my family. Yeah. I'm sure you'll get enough opportunities going forward because I think a lot of things were like this mentor program and all were a little bit slowed down because of COVID. Right. And then, you know, it's amazing that you got through your transplant in the pandemic and then you recovered in the pandemic. You started working in the pandemic and here you are at 18 months after the pandemic, within still in the pandemic. But thank you, Mr. Cockrell. I wanted to thank you and, you know, for doing this excellent presentations with me. And it gives me also a lot of satisfaction to do this. With that, we'd like to conclude this session between us. And then I'm sure if there's questions and answer, we can answer them. Thank you. Great. Thank you, Dr. Sai. Thank you all for joining us today for the dance of the cirrhotic patient, a multidisciplinary team approach, the 2021 Hepatology Associates course. As Don and I planned for this conference, we both wanted to highlight how important it is to have a multidisciplinary team approach to patient care and ensure we had representation from the multiple specialties that we depend on when caring for a patient with liver disease. We were honored to have such amazing speakers who truly represent the multidisciplinary approach that is key when taking care of a complex cirrhotic patient. Each speaker brought their unique point of view in their talk. We were also very proud to have the first patient and hopefully not the last to speak at an ASLV conference and provide a firsthand patient account of their transplant experience. I want to thank all of our speakers and especially my co-chair, Dawn, as this program would not be possible without her hard work and dedication. Thank you all for listening to our course.

Pharmacists

Liver disease

Dosing adjustments

Drug interactions

Herbal supplements

Hepatotoxicity

Education

Monitoring

Liver transplantation

Post-transplant care

Complications

Rejection

Infections

Cirrhosis

Bacterial peritonitis