Hello, thank you for joining today. I'm Renu Dhanasekaran. I'm a member of the AASLD Online Learning Committee, and it gives me great pleasure to introduce our speaker today, Dr. Sumit Asrani. Dr. Asrani is the Chief of Hepatology and Liver Transplantation at Baylor University, Dallas and Fort Worth. Today, we'll be talking about the new AASLD Clinical Practice Guidelines on Acute and Chronic Liver Failure, or ACLF, and the management of critically ill patients with cirrhosis. These guidelines are brand new, were published in June 2024 in Hepatology, and Dr. Asrani presented an overview of this guideline at DDW 2024. And we thank him for sharing his insight with us here today. Dr. Asrani, welcome to Liver Learning. Thank you so much, Dr. Dhanasekaran. Okay, let's start from the beginning. What was the background or the motivation for developing these new practice guidelines? I think that the impetus from AASLD standpoint was that, you know, wanting the guidelines to reflect the reality of the kind of patients that we take care of on a daily basis. And as you know, as a practicing hepatologist, what we're seeing is our patients are getting sicker and sicker, and oftentimes about, you know, one out of three patient ends up in the intensive care unit. And hence, you know, we wanted to work on guidelines which are practical and sort of address this. And so this guideline talks about two aspects. One is, you know, management of patients of acute, with acute and chronic liver failure, and by extension, patients that are critically ill with cirrhosis in the ICU. Got it, got it. Can you share with us like a broad framework of how you define ACLF in this guidelines? Yeah. Yeah, so, you know, one of the aspects is if you look at over time, there've been multiple definitions depending on the region of what we think about is acute and chronic liver failure. And the goal was to say, okay, how can we harmonize some of these definitions? So let me share a framework of, you know, what we thought were key components of thinking about acute and chronic liver failure. So when we think about acute and chronic liver failure, we think about it as patients who have underlying liver disease, whether this is chronic liver disease, compensated cirrhosis, or decompensated cirrhosis. And on top of that, you have sort of this acute insult. And when you have this acute insult, this leads to a rapid deterioration in clinical condition. So already you have to have two components. One is you have to have hepatic failure, which is defined by elevated bilirubin and elevated INR in patients with chronic liver disease with or without cirrhosis. These patients then have this acute onset with rapid deterioration. This then leads to development of not only hepatic, but extra hepatic organ failures. And to define ACLF, you have to have at least one extra hepatic organ failure. So the three components in a way are acute onset with rapid deterioration, two, presence of hepatic failure in patients with chronic liver disease with or without cirrhosis, and three, the presence of at least one extra hepatic organ failure. And then what you can see in sort of this framework that we propose is that there's a time where if you intervene early enough, there is reversibility possible, but the later you wait, this becomes less reversible. So this rapid deterioration is influenced by the systemic inflammatory response. And once you start having the development of extra hepatic organ failures, your choices are if it's not caught on early and not reversible, either A, you do have a subset that recover and may go back to their prior state, but if it's irreversible in a majority of the cases, then you're sort of thinking about is, do I just manage the organ failure? And then we're talking about either palliative care or in selective patients thinking about transplant evaluation. And this is a super useful framework to think of the competence required and also the timeline that is aligned with that. So that's very helpful. What would you, can you talk to us a little bit about key management guidelines for ACLF and any new recommendations that are practical from the guidelines? So one of the things is that since the main focus was that we wanted this to be a practical document, we went through that, how do we manage each of the different extra hepatic organ failures? So in the document we talk about, and this will be available as a link with this conversation of the different organs, but one organ that maybe I can focus on, which is very common in our patients is sort of kidney failure. So here is the framework that we thought about in terms of management of kidney failure. And this is a busy sort of figure, but the three components are, is that when you have a patient with acute and chronic liver failure, who comes in and has progression to kidney failure, step one is really how do we halt the progression? This is through volume expansion, giving albumin and trying this trial over 20 to 48 hours, doing measures that we usually do. For example, withdraw diuretics, take away nephrotoxic drugs, treat the infection, give blood transfusions and prophylactic antibiotics. Second is an early assessment for hepatorenal syndrome. So oftentimes in the past, we used to wait for HRS to develop and we had a longer timeframe between that. But now more and more what we're realizing is that the earlier we act and the earlier we recognize HRS, the earlier we can intervene on it. And three is once we think about halting progression, earlier assessment for HRS AKI, then it's early therapy for HRS. And one of the things that has changed now compared to even five years ago, at least in the United States, is the availability of Terlepresin. So in this document, we sort of give ground rules of how to start Terlepresin, how to monitor Terlepresin use in our patients and how to identify if patients are responding to Terlepresin. And then the other guidance document that I would sort of link with this is there's another paper where with ICA and the ADKI committee that we've come up with sort of updated guidance on management of HRS. But so here's an example of, you know, one of the organs that we discuss of how to manage in patients with acute and chronic liver failure. Yeah, thank you for that. So one other question is we all know these patients can be very sick. So can you give us your opinion and a way to approach the role of liver transplantation in ACLF? And that's the third aspect is, you know, besides the framework, besides organ management, the question was, you know, how do we define the role of liver transplantation? So if you look at management of patients in general in the intensive care unit, over time that has evolved. If we look at the last 10, 15 years, we have studies that show that it used to be that mortality of liver patients in the ICU was much higher. Now, over time, that's normalized and outcomes in selected patients that undergo transplant, even from the intensive care unit is as good as compared to other indications. So there's more awareness that even in critically ill patients, we should consider liver transplantation. We did not go as far as saying that patients who are in the ICU should get additional points if they have acute and chronic liver failure because of many other reasons. But in selective cases, we should consider liver transplantation. However, for that to happen, patients have to meet certain criteria. So I'll walk you through the framework that we thought about is, so if you have a critically ill patient with cirrhosis or coming in with acute and chronic liver failure, central to their management, yes, is organ specific management. It is also palliative care. So involving a palliative care early on in patients with acute and chronic liver failure is important, whether this is discussing with a specialist or at least having the discussion with the family because at the end of the day, patients with ACLF continue to have high mortality and most will not be transplant candidates. So having the discussion early on is extremely important. Having said that, I think giving everybody the opportunity to be considered as a liver transplant candidate is equally important. So organ specific management, early palliative care consultation and assessment for liver transplantation. We can do this by using liver specific risk assessment tools, by having a baseline measurement and then serial measurements. Now, in these patients, if there's already progression to four plus organs being failing or mark increase in reflective predictive scores, then that's the time where you think about hospice within, let's say within a week. However, if you are able to achieve stabilization or improvement of organ failures, such as improvement in respiratory failure, hemodynamic stability, controlled infection, and if there are no other contraindications to transplantation, then I think transplantation should be considered. However, the caveat is one should anticipate that patients with ACLF that undergo transplantation will have increased resource utilization and morbidity after transplant. So the transplant team and the system needs to be prepared for that possibility. Wonderful. Yeah. Thank you so much. And, you know, overall I read through this document and it's a comprehensive cover, several other aspects that we don't cover in the conversation today, from nutrition to when palliative care is important to when role of antibiotics and transplant. So congrats to your team on this wonderful guidance document will be super helpful to us in practice. Thank you so much for joining us today and having this discussion. Thank you.

ACLF guidelines

organ failures

Terlepresin

liver transplantation

palliative care