Good afternoon, everybody. My name is Guadalupe Garcia-Azao. I'm from Yale University and VA Connecticut Health Care System. And I'm introducing you to, well, actually, this is the course director, Natalie Torok. And I'm introducing you to my co-moderator, Shiv Sarin, from the All India Institute in New Delhi. So our last session, and last is not least, is entitled Cirrhosis as a Systemic Disease, Challenging Insights and Future Directions. And we're going to have four great lecturers, which I am going to invite to come up to the table now, please. Jennifer Lai from UCSF, Andres Duarte Rojo from Northwestern, Nneka Uferi from MGH, Mass General, and Rohit Lumba from UCSD, and finally, Pera Ginés from the University of Barcelona. A great panel. So if you can give me the case first, please. So the case is case number four. It's called Getting Weaker. So this is a 69-year-old man with metabolic standard hepatitis cirrhosis and ascites who was listed in August of 2022 with a MELD of 15. Over the course of the last year, he has had two hospitalizations for fluid overload. His liver frailty index, as you can see in the graph on the right, has been rising, was 3.9 previously, and has worsened to 4.5, which is borderline frail after these two hospitalizations. He is now admitted with ten ascites and an esarcha. So the past medical history is relevant for class two obesity. He has a BMI of 39, type two diabetes, hypertension, and atrial flutter. The diagnostic has a MELD of 18, and his six-minute walk test is 150 meters. That is, he is severely compromised. So can we see the questions now? And prepare yourself for this slide, all right? There's some instructions somewhere for you to do the slide, but at this point, you should know how to do it anyhow. So will a liver transplant improve this patient's prognosis, yes or no? The second one is, what should be the end point for the assessment of treatment response in a MASH cirrhosis trial? I apologize for that one. It's A, improvement in frailty, B, reduction in the rate of hepatic decompensation and liver-related mortality, C, regression of fibrosis, D, improvement of liver stiffness on FibroScan. Then the wife comes and asks, what could have been done before he got to this stage, right? To impact his prognosis, a diagnosis of chronic liver disease should have been made six months before, one year before, three years before, or who knows? So go ahead and answer the questions, and we'll go one by one with your answers. And then the experts on the floor will give us some idea of what the answers to these questions are. So can we see the answers to the first question? Will a liver transplant improve? So most of you, it's almost 50-50, but most of you would say that yes, the patient would benefit from a liver transplant at this point. And the second one, so Dr. Lai and Dr. Duarte will, Dr. Rojo will discuss, will have a debate about this issue entirely. So what should be the end point for the assessment of treatment response in MASH-NASH cirrhosis trials and reduction in the rate of hepatic decompensation for more than two-thirds of the people? And Dr. Lumba will be talking about the answer to this question. The third question is about the wife asking, what could have been done before, and what is the time frame for when should this diagnosis have been done? And who knows is the majority of the patients. We have Dr. Nneka Ofer who will talk about the holistic care of these patients, and we'll be probably able to determine this. And Dr. Ginés will give us, at the end of this lecture, the whole sort of the summary of what you've been hearing so far is called, this session is called, you know, back to the future is like, where are we now, how do we get to the point where we are right now? Thank you, I'm very grateful to the organizers for having invited me to moderate this session with my dear colleague, Professor Garcia, and the best of the panel here. And the three questions chosen, I'm sure all of you have paid attention, really mean that these are debatable issues, and that's why this case has been picked up. The case was 69-year-old, and by the time he actually, if at all, goes for transplant, he would be 70, he's frail, and also has comorbidities. And therefore, there is need for a debate, and we have two of the best wrestlers around, so I'm inviting the first wrestler, Jennifer Lai, from UCSF. Should frailty be considered in prioritizing liver transplant candidates? Yes. Thank you so much to the organizers for the invitation to be here. I've been working out for this. It's really such an honor, in particular, to be debating against the brilliant Dr. Duarte Rojo, who is not only a collaborator and a friend, but today is my formidable opponent. So may the best man or woman win. So I will be arguing in favor of frailty being considered for prioritizing liver transplant candidates. So I have a question for you. What do you think is the single most important number that determines how you manage a patient with cirrhosis in the context of liver transplantation? I'll bet you that most of you are thinking about this number, the MELD score. But I would propose that there is another number that supersedes the MELD in importance, because it determines the entire way that we allocate livers and prioritize patients for liver transplantation in the United States, and that is the number nine. Number nine represents the OPTN policy number that governs the allocation of livers nationally, and specifically states that each liver transplant candidate shall be assigned a score that reflects the probability of death within a three-month period. This score, as we all know, is the MELD score, which is a single number that captures the risk of death within the next three months, largely from liver-related factors. But over the last decade, there has been increasing recognition that another factor, frailty, also strongly predicts the probability of impending death or decompensation in patients with cirrhosis. Frailty is classically defined as a distinct biologic state of decreasing physiologic reserve and increasing vulnerability to health stressors that results from and represents the accumulation of an individual's health deficits over time. It's a construct that originated in the field of geriatrics to capture the sum total of the multiple comorbidities that older adults so often experience, such as are represented here in this orange box. But in patients with cirrhosis, there are a number of conditions related to the cirrhosis itself that can also contribute to frailty, such as the underlying etiology, ascites, hepatic encephalopathy, the catabolic state, systemic inflammation, and hypogonadism, just to name a few, that can make our patients with cirrhosis seem physiologically old, even if they're not chronologically so. And when either these liver-related conditions or these non-liver conditions are in their more chronic and their advanced states, they can then lead to this alternate pathway to frailty through malnutrition, muscle wasting, and disability. In patients with cirrhosis, whether chronologically old or young, frailty is strongly associated with death. This is demonstrated here in this study of an international multicenter cohort of ambulatory patients with cirrhosis and frailty assessments, which shows that patients who were frail experienced a greater than twofold increased risk of death or decompensation on the wait list compared to those who were not frail. And from this survival curve, you can see that this increased risk occurred not just at 90 days, but also it continued even up to a year past the baseline frailty assessment, suggesting that it may be even a better prognostic marker and more useful in clinical practice than the MELD score alone. Another study demonstrated that patients with lower MELD scores who were frail had a risk of mortality that was similar to patients who had higher MELD scores who were robust, a risk that was equivalent to nine MELD sodium points of excess mortality above and beyond what would have been predicted by their laboratory MELD score alone. So with these data in mind, let's return back to our patient. So you'll recall that he is a 69-year-old man with hypertension, diabetes, atrial fibrillation, and MASH cirrhosis. And we met him about a year ago in August of last year with a MELD score of 15 and listed him for transplant. And he has subsequently had a couple of hospitalizations for worsening portal hypertensive complications and now is in our hospital with fluid overload and a MELD score of 18. So that is his liver-related history of present illness. Let's focus on his frailty status. At the time of listing, his liver frailty index was 3.94, which does not meet criteria for frail and, in fact, is not even that bad as it corresponds to about the 50th percentile of liver frailty index scores among ambulatory liver transplant candidates in the United States. So let's put these data into the frailty framework to practice some personalized medicine. Despite his more advanced age and medical comorbidities, in addition to his cirrhosis and his MELD of 15, his lack of frailty suggests that these medical comorbidities had not accumulated to lead directly to frailty or had they been advanced enough to lead indirectly to frailty through this alternate pathway of malnutrition, muscle wasting, and disability. So at this very moment, when we first meet this patient, he has good physiologic reserve to withstand the upcoming transplant surgery and should be considered a good liver transplant candidate. Now let's move forward in time across a one-year period during which our patient was hospitalized multiple times for worsening portal hypertensive complications, and this chipped away at his physiologic reserve as evidenced by a worsening liver frailty index, now meeting criteria for frail, and a very poor six-minute walk test distance. Bringing this back into the frailty framework to make this more personalized, we can see that the only thing that has changed in the course of the year, except for one year of chronologic age, has been his increasing burden of cirrhosis and portal hypertensive complications. So at this moment, when we see him in the hospital, it is reasonable to assume that it is the liver condition that is leading to his frail phenotype today, and that is what is predominantly driving his risk of death. So here's the thing. This is exactly why we offer liver transplant, to cure the cirrhosis and portal hypertension and any risk of death that would come from the liver-related complications. Now at this point, some of you may be thinking, but Jen, I thought that frailty was associated with worse outcomes after transplant. So why would I want to prioritize a frail patient for liver transplant? Well, you're right in part. There are data to suggest that frailty is associated with worse post-transplant outcomes, as is shown here, in which pre-transplant frailty, as measured in the ambulatory setting, is associated with a greater than two-fold increased risk of post-transplant death. But let's delve deeper into the data here and look at the actual survival rates. Sure, frail patients did experience statistically significantly lower survival than those who were not frail, but their survival rates were quite acceptable at one, three, and even five years after transplant. So it's clear from these data that the question is not whether we can transplant a frail patient, but how can we offer liver transplant to these patients to achieve acceptable outcomes? Which brings me back to the number nine, policy nine, that is, which dictates how we prioritize patients for liver transplant, with the MELD score. But we all know, as clinicians, that there is a subset of patients for whom this single metric does not accurately reflect the probability of death within the next three months, as was so illustrated perfectly by our patient, who, despite his multiple hospitalizations for worsening portal hypertensive complications, had a MELD score of only 18, which is generally a MELD score that is too low to receive a deceased donor liver offer under the standard liver allocation scheme in the United States. If only we could add the nine MELD points of excess mortality risk to our patient's priority score, we could allow him to access a life-saving liver transplant in a timely fashion. Allowing our frail patients with higher priority on the wait list would enable us to transplant them early, when we believe that their manifestation of frailty reflects the accumulation of largely their liver-related health deficits and could be reversible with a liver transplant, and before they become advanced enough to lead to the more irreversible complications of severe malnutrition, muscle wasting, and disability. So in conclusion, should frailty be considered for prioritizing patients for liver transplantation? If you believe that frailty is a major factor that contributes to excess wait list mortality and could offer our patients a timely access to liver transplantation in order to save their lives, then please vote yes. Thank you very much. For the con, Andres Duarte-Rojo from Northwestern is going to give us the fight back. Well, thank you, everybody, for being here, and thank you to the organizers for the invitation. It is indeed a great pleasure to spar Jen Lai, who is a good friend. We basically share a lot of the view on frailty, but not today. All right. So I think most people know me. I'm at Northwestern, as Lupe just said. These are my disclosures, and my other disclosures is that it's really a great pleasure to be sparring today with Jen Lai. So let's go to the case, and let's just—I want to tell you one little thing about a patient like this that we actually transplanted. So this patient was added to the transplant wait list back in August of 2021, got transplanted, and one month after transplant, this patient was doing okay, able to do the activities of daily life, back to almost a normal fitness, and definitely a normal graft function. So we are already transplanted these patients with frailty, and we are not needing any extra points to get them to liver transplantation. So I want you to think about that. It is indeed, as Dr. Lai say, that frailty has an effect of mortality. So I often tend to my patients when we are rounding—to my patients, to my trainees, sorry, when we are rounding—that if you believe in melt, you have to believe in LFI or any of the frailty parameters that we use as a predictor of mortality. And here, you can see how close the area under the curves are for predicting mortality on the transplant wait list. And just like Dr. Lai said, it actually kind of predicts a doubling of the mortality for a patient who has frailty versus a patient without frailty for the same melt score. So it kind of makes sense that we need to prioritize these patients. But the issue is that the rules have changed. A lot of this data was generated with melt or with melt sodium, and the data is now changed. We now are using melt 3.0, where we added female sex. We added it as a prioritizing criterion. We also added up albumin, and we capped the creatinine. You can see that even though the C-statistic for melt versus melt sodium—melt 3.0 versus melt sodium—is not really changed, there was a reclassification of 9% of the patients in whom death was more accurately predicted. Most of them were women. That's why this method is working better. And importantly, if you actually review some of the studies, and this particular study from Dr. Lai, you will see that the patients who were reclassified based on the addition of melt sodium and frailty were precisely female. Half of them were female, and these people also have lower albumin. Frail people have a lower albumin. So we kind of already are taking care of this just by introducing melt 3.0, and the impact that frailty has on the predicted mortality of melt 3.0, we don't know it yet, so we need that data before we carry on with any changes to our allocation system. In fact, just think about it, sex and albumin within the MELK 3.0, I mean, that's exactly what frailty people have. Women have more frailty, have a worse liver frailty index, as Dr. Lai is proposing, and also have lower albumin. So there is a common theme in here where this is really important parameters, and continues distribution for liver allograft allocation is also coming down the road. For those who are new to this term, the CDO continuous distribution will basically incorporate other parameters that are important to predict mortality, like, for example, other variables associated with candidate biology, frailty, by the way, is not going to be included, and other parameters that can have an impact on the patient access to liver transplantation. In fact, the OPOM, or this Optimized Predictor of Mortality, has already shown that it's better than the MELK 3.0 and the MELK that we have been using. It better predicts the death, especially in the people who are quite ill. So the funny thing is that this OPOM, this new model that is better than MELK, or was shown to be better than MELK in this study, one of the two variables that it included, one was sage, but the other one was albumin, and exactly what they did is that they included albumin at different time points, and that's exactly what MELK 3.0 is doing. So again, some of these parameters that are associated with frailty are part of MELK 3.0, and we really need to further explain what's the effect of this and continuous distribution when this gets implemented within the next couple of years, to really understand if we do need something extra to prioritize the sickest and likely the frail. So a little bit of role-playing here. If you come to me and ask me, and I'm a UNOS policymaker, hey, we need to include frailty for allocation, I will tell you, this is premature. Let's just wait, what are the implications of MELK 3.0, and actually, let's see what happens with CD in the future. Also, this is likely redundant, because if you think about it, frail patients are already being prioritized, that profile is already being prioritized with the current and the upcoming allocation system. Dr. Lai already showed this chart. This is a very important study, because just like we said that frailty does impact on pre-transplant mortality, the effect on post-transplant, to me, is not so clear, and she already mentioned that, because this 3% difference, to me, is not clinically meaningful. What is clinically meaningful, though, is that patients that get to transplantation with frailty have higher healthcare utilization. In particularly, they spend more days in the hospital, including the ICU, and they are discharged to other place that is not home, usually a rehabilitation center. We have to consider that the time on the transplant wait list really has placed a very important role in what the association is between frailty and pre- and post-transplant outcomes. In this recently published study from Spain, the group from Dr. Marina Berenguer, where, by the way, the wait list time is 2.6 months, they showed that there was no association between frailty and pre-transplant mortality. You can see, actually, in this Kaplan-Meier, this is the robust group, so no association whatsoever. We can confirm, however, that frailty patients do have a higher healthcare utilization after liver transplantation. For the last 10 years, we've really been working pretty hard in the United States and throughout the world to reduce the time of patients in the transplant wait list. So from having an average time of over a year, we're really now only at 7.5. Actually, in our organ procurement organization, in our area, it's 5.1, and my center is 3.3. So it's quite different to 2.6. So I don't see how frailty will really impact these patients. And even if there is an impact in some of the centers, you know, imagine how disparity there will be with some centers that have a wait list time of 15 or 20 months versus those centers that have a wait list, a time on the wait list of only 3 to 5 months. So again, dropping the wait list time in the USA, a great effort that we've been doing over the last few years, with that, the impact of frailty is even less predictable on top of what I already discussed on the MED 3.0 and CIV. So if I were an OPO director, and again, you ask me, we need to include this in our allocation method, I will tell you, let's focus better on increasing organ recovery and shortening the time of the transplant wait list. That's where we need to put the money on. And I will actually just reply back to you and give you some food for thought. If we include frailty as a parameter, we actually might have, create some disparities in terms of equity to transplantation, and we actually might also affect the offer acceptance practice. And I really can think of my surgeons going to the, having an extended criteria donor and going to the transplant wait list and say, cannot give it to this patient, he's frail, cannot give it to this patient, he's frail, et cetera, et cetera. So likely, all these acceptance organ policies that we are following will also be affected. So with a little bit of pretend play, let's just assume that frailty is included in the allocation. And I'm going to show you two clinical scenarios where it will definitely not work. This is a 39-year-old. He ended up with rhabdomyolysis and ICU neuropathy. Most of the time he spent in the hospital, including 30 days in inpatient rehabilitation prior to transplantation. Four months post-transplant, patient is doing well, still uses a walker, however, this patient got transplanted, and got transplanted with a melted sodium of only 20. So the thing is that frailty is a very complex construct, and there is not one tool that fits everybody. We have various ways of measuring frailty, cardiorespiratory fitness or function. We have LF5, six-minute walk test, SPPB, gait speed test. Which one of those is the one that we're going to utilize to give priority to our patients? Because all of them fail in different circumstances, as I'm showing here on this table. Now, Dr. Lai already explained to us that the whole idea of including frailty is that it tells us what is the physiologic reserve of a patient, and it tells us about vulnerability and resistance to stress. Now, the original proposal of frailty by Dr. Freed, just like Dr. Lai presented, included many other parameters. And we basically got rid of all of them, and just decided to include or focus on physical frailty. And we got rid of some parameters that actually might tell us about what the resilience of our patients is to just tolerate some of this vulnerability. Very importantly, we have to know what is the chronicity and the trajectory of these patients before we take any decision, because these are key to assess the physiological reserve. This is a study that we did with over 500 patients where we tried to identify which are the parameters associated with frailty. Age, of course, is very important. And again, sex, females, and albumin, very strongly associated, actually the two parameters most strongly associated with frailty. But we don't have still any data on what acute and chronic. We don't even know what is acute and chronic, but we know that when somebody was doing okay in the clinic last month, and now is in the hospital with frailty, that patient is going to do well, perfectly well, after transplant. So about trajectory, there is another beautiful study from the Frailt Consortium where you can see that improved frailty will improve your survival, and if you worsen the frailty, that also will affect your survival. So frailty, it's not just like a unique measure. We need to know how it changes over time. This was, of course, shown on a multivariable analysis as significant in the study. So if I were a regulatory manager and I had to include a frailty parameter to just determine who of my patients is going to get this exception, these nine points that Dr. Lai is proposing, I will say that frailty is an oversimplification of physiological reserve. Physiological reserve is more complicated than that. What tool am I going to use? What cofactors are going to be considered as modifiers of my frailty score? And in the end, one measurement is not enough. We need a trajectory. So back to the case, I can tell you that it will be unfair to give this patient extra points when this young male could just tolerate an extended criteria donor, and that's exactly what we did for this gentleman. So case number two, this is a prehabilitated individual. This is a patient who, by the way, taught me that maybe it was not a good idea to call people frail or to tell people that they had frailty because he associated this with weakness. And what I want you to see here is that when his LFI was 4.86, he was walking very little. We gave him an activity tracker. We tracked his steps. We made him rehabilitate for a six-week period, and we were able to get him to almost 4,000 steps per day. At that time, his frailty score, the LFI, has dropped, and he was no longer frail. He underwent very good transplantation, and he had no issues whatsoever. So we have shown that rehabilitation is possible in these patients and that the LFI can be improved even with teleprehabilitation, and the six-minute walk test also improves up to 40 meters, which is a clinically significant parameter. Most importantly, in this study, we actually show that patients were able to increase their daily steps from 1,200 to 3,500, almost triple. And what I take from that, and this is why I think this is so important, is that these patients are showing us that they have physiological reserve left in them, and that's what we need to know. We need to know that, and we need to know what their engagement is going to be so that they can recover with rehabilitation after liver transplantation. So we know the frailty metrics are reversible, and there is a systematic review here where you can actually look at some of the studies. Most importantly, if patients on the transplant wave come to see a physical therapy, they actually improve their survival, and that's what I'm showing here in this multivariable analysis, and this is irrespective of their frailty. So physical therapy improves waitlist survival. So this is my last argument, or my last role modeling argument, that if I were a transplant hospital administrator, and we're going to implement this policy, I will tell you that this was just disincentivized rehabilitation. Right now, we have to put money for rehabilitation either before or after transplantation, but if I were to incentivize the frail patients, I will likely get fast-track patients who are frail post-transplant and have to spend more money, more time to that group of patients. So in the case of this patient, it also will be unfair to decrease or eliminate those nine points just because he improved after rehabilitation. Not all candidates with frailty are created equals. Some need to demonstrate their physiologic reserve by engaging in this rehabilitation, and we should not deny patients and transplant centers with that opportunity. To conclude, I've shown you through four different role modeling that this doesn't make sense. We just don't have sufficient data. We could affect equity. We could also affect principles and acceptance practice. Instead of frailty or physical fitness being used to prioritize transplantation, we should use it as an indication to rehabilitation. Thank you very much. So the people will have to decide who wins and who does not. But maybe both are winners. Such an excellent debate by both of them. Congratulations. And now it's my pleasure to invite Dr. Nenka Ufre from MGH for giving this presentation, Holistic Care of Patients with End-Stage Liver Disease. Keep your questions ready. You can always do that and post your questions so that we can take it at the end of the session. So I would like to thank the organizers for this invitation to talk about holistic care of patients with end-stage liver disease. So by the end of the session, you should be able to assess and address the holistic care needs of patients with end-stage liver disease to improve their quality of life across the following four domains, physical, psychological, psychosocial, and existential. So a lot of our discussion during this session has really centered on the case of this man, 69-year-old man with MASH cirrhosis who has progressive frailty. But I want us all to take a step back and really look at this man's lived experience as well as that of his family at the time that he developed decompensated cirrhosis. So he probably lived with MASH cirrhosis for a long time and had known about it, but then suddenly developed ascites and transitioned to a state of decompensated cirrhosis. And one thing that is important for us to remember is that his life completely changed once he developed ascites. He has had three hospitalizations that have happened over a period of months, not even a year, and it is likely that him and his family are wondering, I am on the liver transplant waiting list. I am continually being hospitalized. I am losing my functional status, and I am really worried about the future. And he should, he has every reason to be worried as well as his family. So we all know about this natural history study looking at the prognosis of our patients with cirrhosis that showed that patients with compensated cirrhosis have a median survival of over 12 years in the absence of liver transplantation. But we know that once our patients develop decompensated disease, their prognosis is much shorter, on the order of two years in the absence of transplantation. However, for our older adults with cirrhosis, their prognosis is even more guarded. For adults 65 years or older, we now know that those who have hepatic encephalopathy have a median transplant-free survival of a year, as well as those with ascites. And for this man, he is now on his third hospitalization and has 10 ascites requiring paracentesis, and that portends a median survival without transplantation of just four and a half months. And so he's worried, and likely we as his clinicians are worried too. But we also have hope for him, because we know that there are rising rates of liver transplantation amongst older adults that have occurred over the past decade, looking at PTN data and the line in green with the Xs. And so this man is on the liver transplant waiting list. He has multiple medical comorbidities, but we are transplanting patients who look just like him at a higher frequency over the past decade. So a lot of our focus as hepatologists is really at this period. Our entire debate really focused on his frailty has progressively worsened, what is his likelihood of getting to liver transplantation, will he be able to get through that period? And what I want us to instead do is I want us to take a step back and really sit in the lived experience of this patient and what happened at the time that he first was diagnosed or developed ascites. And that's the fact that this man has significant symptom burden. He has incredibly high health care utilization three hospitalizations in just less than a year and he also has significantly poor quality of life and So right now our current health care delivery models are not effectively meeting the needs of our patients with decompensated cirrhosis And so how can we start to identify those needs of these patients and their families? I think this requires us to step into their shoes and understand the journey of living with cirrhosis And so in our group, we performed a qualitative interview study of patients with cirrhosis and their caregivers to really ask them What their lived experience has been ever since they were diagnosed and One of the things that they said is that they wish that in addition to their ascites and other symptoms of liver failure That their hepatology clinicians would also focus on the other physical symptoms and psychological symptoms that they were suffering from So this is a systematic review and meta-analysis that lists the symptom frequency of patients with cirrhosis As compared to patients with cancer and as you can see here particularly for symptoms like insomnia and fatigue and others that this patient may be suffering from Our patients with cirrhosis have a physical and psychological symptom burden that approximates and at times even exceeds that experienced by patients with cancer At the time that this patient was diagnosed he may have said something like another patient said to our group Who said my stomach was kind of swelling up. I was getting uncomfortable I didn't realize I was actually filling up with fluid and I finally looked in the mirror and I was like, yeah I don't look that great and I went to the hospital and at that point I was pretty far along and this was a story that was repeated by almost every single patient and caregiver that we interviewed and It highlights that this diagnosis of decompensated cirrhosis is shocking for patients We are very used to seeing our patients look incredibly sick but to suddenly develop ascites to have an episode of variceal bleeding feels like it comes out of nowhere for patients and families and As they go through their course, they said things like this when I was diagnosed. I didn't know anything about it I didn't know anyone who had it and I didn't know what to do Basically, I started to do research to find it It would have been helpful if my doctors had said look into this look into that When I was diagnosed, they just said you have liver disease. You've got to see a doctor They didn't even give me any information at all. Not even what cirrhosis is and so our patients are going through this journey and this patient probably has had a significant delay in his understanding of his illness and his understanding of cirrhosis and This leads to recurrent hospitalizations that is this patient for example has experienced an emotional distress Where patients say things like I feel like I'm dealing with depression on a daily basis as well as their caregivers suffering as well Saying things like it's like being blindfolded on the biggest rollercoaster ride of your life Wait a minute and it will change and it's only going to get worse. I guess I need some more coping skills and Then a theme that came out so profoundly during our interviews with patients and families was the fact that our diagnosis of cirrhosis is financially toxic to them many of them said I can see a lot of people would be my age and not be able to afford insurance and having to decide whether they can take these meds and Patients and family sharing with us that they oftentimes had to make decisions between taking the medications we prescribe them or putting food on the table or paying for their rent and So it is in this setting that things like the shock of that initial diagnosis and our patients delay in their illness understanding worsens their high symptom burden Making decisions between paying for your meds and taking them versus food rents and more leads to those medications not being taken which results in our patients being Rehospitalized and Then the emotional distress that our patients and their caregivers face contributes to both of them as a dyad experiencing poor quality of life And so I've shown you these problems, but how can we start to talk about solutions? How can we talk about how to deliver holistic cirrhosis care in our clinical practice? So one important solution is that we need to start to enhance our patient and caregivers illness education and understanding When we asked patients in our study What are the things that you wish you knew at the time that you developed decompensated cirrhosis? They gave us three resources them and their families First they wish that they'd had a discharge checklist that when they came into the hospital and then were discharged They were prescribed at times five new medications to manage their decompensated disease And they had no idea what those medications were what they were treating and what they could cause Secondly anticipatory guidance for future warning signs One patient said pretty profoundly. I was admitted to the hospital with the CITES and no one told me that hepatic encephalopathy Would be around the corner when I left the hospital and if I had been prepared for that that would have made my life easier Caregivers also stress the importance of having them be involved in the process of their loved ones discharge and in the education Process too as they are our front line in taking care of our patients with cirrhosis One website that I think many of us in the room know about but if you don't I encourage you to look at it It's a website called cirrhosis care. And so this website was created by dr Punita Tandon at the University of Alberta And this is a website that is really focused on the mission of improving the quality of care And I would also argue the quality of life for patients with cirrhosis on This website there are multiple resources that patients and families can engage in including short videos and reading topics About living with cirrhosis as well as wellness education related to nutrition exercise and more and so I provide this website and tell my patients and caregivers in clinic To go to this website to learn more about cirrhosis But we also need to make a big step and start to assess and treat symptom burden again, our patients suffer from many non liver failure symptoms that are not typically assessed in our clinical practice and So scales that I use in my clinical practice, especially the first one is the Edmonton symptom assessment scale And so this is a 10 item scale that patients can complete in less than one minute That provides the severity of symptoms that are all listed on that column there and you may be wondering I don't want to assess any symptoms if I don't know how to treat them and I completely understand that But I will point you to two resources that are at your fingertips Where you can start to make initial steps for symptom management and so one is back to that cirrhosis care website that has a Practitioner pathway that lists tips and non pharmacologic and pharmacologic Approaches to symptom management, but for both physical and psychological symptoms that our patients may face I'll also point you to our recent ASL D practice guidance on palliative care and symptom based management in Decompensated cirrhosis that also has a number of helpful tips and resources For many of the physical and psychological symptoms that our patients face But I'll also say that there is a need for increased symptom science and cirrhosis care Next we need to proactively screen for financial distress and one question can be asked of our patients Are you having difficulty paying for your medical care? And this may lead us to involving certain groups or performing certain actions Within our clinical practice a way to treat financial distress is to deprescribe Unnecessary medications and so that is something that each of us can do easily in our practice Availability of social workers and financial navigators is obviously quite limited But in the transplant setting we should also see them as our colleagues as part of the transplant team in Helping us to proactively address financial distress and then obviously the use of telehealth as opposed to in-office visits helps to save our patients travel burden and online resources Another resource that I use that I think many of us have heard of is Mark Cuban's cost plus drugs websites To find the lowest costs for medications that our patients are often prescribed And so for example for this patient with ten societies where we're likely going to be prescribing him Spironolactone if he's able to tolerate that Going on to mark website onto this cost plus drugs website You can see that we can save our patient $30 a month over $300 a year in a medication that we prescribe routinely if we just take that extra step of Trying to find him a lower cost medication Lastly we need to start to assess and treat patient and caregiver distress Easy screens to use in our clinical practice or to question screens like the phq2 and just simply asking caregivers I know this must be hard on you. How are you doing? and again reaching out to supportive care groups like psychology and psychiatry for those patients who screen positively on phq2 and looking at our primary care colleagues as individuals who can also help to provide extra layers of support and Referrals to local Sub-specialists is very important What I will emphasize is the role of home-based palliative care and home health care in Improving the lived experience of our cirrhosis caregivers who so often feel very burdened in the care that they have to provide on a day-To-day basis And so I just want to say that delivering holistic cirrhosis care requires us to know our local supportive care resources and network and to build collaborations with other supportive care Providers, but before you do that just know that there are things that you can do at your fingertips All of us as hepatology clinicians can do the things in the boxes in red to help to improve our patients care So I want to end with just focusing on this question mark Because this patient is progressively frail He's on the transplant list and the big question is what comes next? There's a lot of prognostic uncertainty and likely existential distress that he's experiencing And so I want to introduce to all of you a communication framework called best case worst case So we know for this man that there are two pathways that he's going to face He's either going to be well enough to get a liver transplant, or he's going to be too sick to get a liver transplant But we don't know which pathway he's going to face over the next few months and So best case worst case is a way for all of us to help to Navigate patients through the different futures they can face in the face of significant prognostic uncertainty and so it first involves the use of a graphical aid where you have a star at the top a square at the bottom and a circle in the middle and you plot the best case the worst case and the most likely case and Then you engage in scenario planning and so scenario planning is a is a fancy way to say Storytelling and essentially what we do is we translate that prognostic scores that we know the clinical judgment that we have Our understanding of this patient's comorbidities and frailty and we translate that medical prognostic information into Functional prognostic information centered on quality of life and we use that information to generate stories And I'll show you an example as applied to this patient in the next slide But at the end of doing that in describing the best case scenario the worst case scenario and the most likely scenario We then assess our patients goals and values and we ask him What is important to you now and oftentimes patients care about whether they're going to have additional Disability are they're going to be able to be at home or be frequently hospitalized or be in rehab And what is their duration? What time do they have left? and So let's apply best case worst case to the context of this patient We need to avoid medical jargon no statistics Describe time using ranges and really focus on duration disposition and Disability and so one way you might frame this conversation with this patient might be as follows What we are hopeful for is the best case for you in the best case You would just wait a few more months for a liver transplants and in the best case you would have just a short days to week Transplant hospitalization and be able to be discharged home You'd experience a few months of recovery and in the best case you'd have minimal side effects and complications from your transplanted immunosuppressant medications and you'd be able to return to an active life living several likely over a decade and Then you have to ask them permission about the worst case because that can be very distressing So you can say would it be okay if I told you what we're worried about and if they say yes You can say well what we're worried about is the worst case That even with you being on the liver transplant waiting list you could continue to have these frequent prolonged Hospitalizations and there may be a point at which you get so sick so frail that you're going to be too sick to get a liver Transplants and when we know that we will know that your time is short And so you may be wondering how do we address the most likely case? Well, we know that this man is frail and so using some of the information that's been generated by dr Lies data research as well as mentioned by Andreas We can say that the most likely in the setting of a patient who's so frail is that he's still going to have a prolonged Wait for liver transplantation and that he's going to be in the hospital for a long time after that based on that data That was just shown and he's likely not going to be able to be discharged home but instead be discharged to a rehab or nursing home and you can tell him that his Rehabilitation will be long. He'll likely experience moderate side effects from his immunosuppressants And while he won't get back to his prior state of living prior to transplantation in terms or prior to his cirrhosis he will achieve a new normal and live for a few years after his liver transplants and so then you can ask him what is important to you now and In hearing what is important to him? This might prompt you to reach out to other colleagues to help to better support him and his family And so how would we manage this patient's physical psychological psychosocial and existential care needs? So you've been able to provide the patient in this wife's cirrhosis education through cirrhosis care.ca You found him lower cost prescriptions through costplusdrugs.com Working collaboratively with his PCP. He's referred to a psychologist Who's encouraged him to participate in a virtual mindfulness program, which has helped to improve his sleep energy and mood Both he and his wife are receiving home health care and home-based palliative care and feel prepared for the future Both with and without liver transplantation. He's able to undergo a successful transplant a few months later So the key takeaways are that anyone can deliver high quality cirrhosis holistic cirrhosis care through improving our patient and caregivers illness understanding symptom burden patient and caregiver distress and financial distress and building bridges of collaboration with our local supportive care networks can help us in the delivery of holistic cirrhosis care and Then lastly the best case worst case is a promising communication framework to address existential distress and prognostic uncertainty and cirrhosis care Thank you

end-stage liver disease

cirrhosis

liver transplant waiting list

holistic care

patient education

symptom screening

financial challenges

caregiver support

communication framework