Dr. Sean Koppe (Host): Welcome to Better Edge, a Northwestern Medicine Podcast for physicians. I'm Dr. Sean Koppe, one of the transplant hepatologists here at Northwestern. And I'm joined today by four of my outstanding colleagues here at Northwestern from the Northwestern Medicine Digestive Health Institute.

We have with us today Dr. Andres Duarte and Dr. Laura Kulik and Dr. Amanda Cheung and Dr. Sarang Thaker. The purpose of the podcast today is to highlight their favorite articles from the past year. I basically asked each of them to choose one article that they thought would be of value and importance to share with some of the practicing clinicians in the community.

I really only put two guide rules in place. One is no mice or rats. Nothing against the great basic science. Work that's being done out there, but we really wanted to focus on clinical information. And then, the other is not to choose any of the articles from the New England Journal of Medicine from 2024, specifically the ones on resmetirom, elafibranor, and also seladelpar-- I always have a hard time saying that one-- all of which were very important articles. But I figured these are maybe articles that people will already be familiar with as well. So, we wanted to choose articles that were maybe out of the things that maybe some of the practicing GIs weren't always necessarily aware of as well.

So with that being said, let's go ahead and get started. First, I'd like to turn to Dr. Sarang Thaker to talk about the article that he chose. So, Sarang, what do you got?

Dr. Sarang Thaker: Yeah. So, this is an article from the American Journal of Gastroenterology back in November of last year, titled Early Diagnostic Paracentesis Improves Outcomes of Hospitalized Patients with Cirrhosis and Ascites. This is a systemic review and a meta-analysis from the group at Indiana University led by Marwan Ghabril. The reason I chose this one, I feel like basic cirrhosis care, ascites, we know how it impacts quality of life, but also lifespan in patients with cirrhosis. You know, it's the most common decompensating event that patients with cirrhosis develop. And we often see delays in getting at least a diagnostic paracentesis for, you know, this core of patients that are often hospitalized. Particularly of importance, we know SBP associated with poor renal outcomes as well as mortality risk and about a third of patients are going to be completely asymptomatic. So, timing of paracentesis is pretty crucial.

So, this study, they grabbed any studies from popular databases and looked at comparing early paracentesis, which is defined as within 12 to 24 hours versus delayed paracentesis. And they excluded studies that most likely had overlapping studies if they're drawn from the same national inpatient sample, for instance, or same time periods. What they looked, the primary outcome was mortality, in-hospital mortality, but secondary outcomes were length of stay, rate of AKI, and then 30-day readmission rates. So overall, they had about seven studies that met their criteria. They had about 40,000 patients, 45,000 in the early group, and 33 patients in the delayed group. You know, all these studies are retrospective cohorts, so not the most rigorous when it comes to scientific exploration, but still a lot of important data from here.

When it comes to the results, kind of what you expected, the early paracentesis group had a significant significantly lower in-hospital mortality. The odds ratio is 0.6. If anyone's interested in the stats, we can talk later. And in a subgroup analysis stratified between paracentesis within 24 hours versus 12 hours, you know, they didn't achieve any statistical significance, but the actual numeric value was lower. Meaning if you had a paracentesis within 12 hours, odds ratio for in-hospital mortality is 0.5 and then, you know, 0.67 for the within 24 hour group. So, not a big difference, but still we compare it to the delayed group. You know, we do see a benefit when it comes to in-hospital mortality. Only five of the seven studies looked at length of stay. Once again, early paracentesis group were associated with lower length of stay. I think it was about four to five days. So, it still means something in the grand scheme of things.

When looking at acute kidney injury, renal insufficiency, only a couple studies looked into this. And once again, early paracentesis group had lower rates of kidney injury compared to delayed group. And then, finally, readmission rates only investigated two of these studies. It was about the same between the groups. It's kind of a wash.

You know, weaknesses, it's only seven studies, right? So, it's kind of a small sample size. There's some biases that are implicit in these types of studies, right? One thing that we don't know is like, when were these patients admitted? I feel like, speaking from experience, it's a little bit harder to get paracentesis on the weekend. So, that's one thing that I specifically was hoping that could be addressed in the future, you know, just to see are there proceduralists around or are hospitalists or GI providers actually doing paras on inpatients? I can speak from experience. I don't, but I supervise residents who do, so... But not every location has trainees, right? Nearly all these studies were done in the United States. So once again, how can you generalize it to a worldwide population? A little bit challenging there. We also don't know how many patients, you know, were given antibiotics prior to paracentesis and do that confound some of the results here.

But I think the big main takeaway is kind of what we always preached, but never really practiced, which is get that paracentesis in, whether it's the ER provider, the hospitalist, the GI, IR if they're available. You know, 50 ccs is enough to significantly impact their course. We already showed, you know, some beneficial data when it comes to in-hospital mortality. But diagnosing SBP is of critical importance as well as not just antibiotics, but the albumin infusion to prevent renal complications. So, I think this article, it shows that we have some work to do, but a good first step.

Host: Yeah. Thanks, Sarang. Definitely something I remember from, you know, 20 years ago in fellowship, always being told, you know, get people tapped as soon as they kind of come in. And honestly, never aware of really where the data comes from. But certainly, it seems like there's good data to back this up. That's a good practice to have. I think the authors mentioned a couple things. You know, one was performing a randomized controlled trial, which I'm not sure that's really realistic.

Dr. Sarang Thaker: Correct, yeah.

Host: And then, the other question I had for you too is, you know, for those patients, like you mentioned where sometimes the timing of when they get their tap versus if they started antibiotics. So, let's say you already have somebody who's been in the hospital for a couple days on antibiotics. You know, do you still tap them at that point? Do you just sort of say, "Okay, I'm going to believe that they must have SBP and complete five days," or any words of wisdom on that?

Dr. Sarang Thaker: Sure. I would still go for it, right? For instance, if you still have SBP despite being on antibiotics for a couple days, you wonder if there's some drug resistance, nosocomial infection. And certainly, you know, the renal protective benefit of administering albumin, which I don't think is done routinely when you're starting empiric antibiotics, right? And I don't think everyone gets the 1.5 grams per kilogram on day one and 1 gram per kilogram on day three.

Host: Putting a teaser in there. Amanda, any thoughts? You'll see if somebody who already is on SBP prophylaxis when they come into the hospital? Do you think that patient still needs a paracentesis when they walk in the door?

Dr. Amanda Cheung: I think so. If you want to be a Negative Nancy, I mean, you don't know if they're even taking the SBP prophylaxis, but let's pretend they are. What this alluded to is maybe there's some sort of antibiotic resistance that's occurring, so I would still plan to do a paracentesis.

Host: Yeah. It seems reasonable. It's also increasingly reported nowadays too, obviously with the widespread use of antibiotics for prophylaxis and so forth. So, now, let's go ahead and turn to Laura with the article that she chose. So, what do you have first, Laura?

Dr. Laura Kulik: So, this is an article that comes from Dr. Tabrizian. It was from six different centers in the United States and it was called The Vitality Study. And the reason I chose this article-- and it was in the Journal of Hepatology in March of 2025, so very recent-- and the reason I chose this study is there's a lot of interest in the use of immunotherapy combined with local regional therapy. So, I am also a part of the HCC Clinic, so it's not surprising that I chose an HCC topic here.

But as we recall, the Milan criteria have been solidified since 1996. So, patients who have a single lesion up to 5 centimeters or three lesions with no one greater than 3 centimeters, no evidence of vascular invasion and no extrahepatic spread, those are patients who in the United States at least qualify for a liver transplantation and upgrade. Some parts of the world are going beyond that. But in the US, we are still based on the Milan criteria.

So, this was an important study because, ever since the Milan criteria came out in 1996, we have been trying to see how much can we push the envelope. And we've been beholden to local regional therapy, which has served us very well. But now, in the last decade, we now have immune checkpoint inhibitors, which unleash the immune system to try to garner some protection from recurrence and keeping the tumor at bay by using your own immune system. So, this was a study of 117 patients. It was prospective. Again, it was from six large transplant centers in the United States and, basically, they prospectively gathered data. These were all patients who were intended to be transplant candidates. So, there was not a contraindication other than their tumor.

The majority of these patients were beyond the Milan criteria, so they had a tumor that was six centimeters or they had four tumors. And so, to get them this upgrade, you have to do a process called down staging where kind of the way I explain it to patients is you shrink them back into that box where you have the limitations of tumor size and number. And also, you have to have an AFP less than a thousand. So, they followed these patients. And basically, 94%, I believe, got local regional therapy plus a form of immunotherapy. And this was from 2016, which is when you had monotherapy like nivolumab, pembrolizumab. And not until we know IMbrave150 that came out a little bit later did we start to see that we're using dual agents, either dual immunotherapy or the use of Avastin in conjunction with immunotherapy or bevacizumab.

So, most of the patients received monotherapy just because of the timeframe. But they showed some really exciting results that the people who needed to be downstaged to receive local regional therapy plus immunotherapy, the vast majority of them were able to be downstaged. So, one, it was feasible. Of the number of patients, about 43 patients went to transplant. So again, this was an intent to treat. So, they started with the 117 patients, and then they followed them as they treated them. So, there were people who dropped out. The people who were always within Milan criteria may say, "Well, why were you giving them immunotherapy if they were within the Milan criteria?" These were people who had received local regional therapy and they didn't have as robust of a response. And we know that your chance of recurrence is highest when you have more tumor on your explant. So, your goal when you're treating people is try to get a complete response by imaging. So, these are patients who had exhausted local regional therapy or still had a high AFP, so they added on the immunotherapy.

So, it's not surprising those who were within Milan were less likely to drop out. It was still in the range of 28%. And those who are greater than Milan, it was 48%. So, we know that we're starting from a group of people who are less likely to get into the Milan criteria. But of those who did, the ones who did get transplanted, they did show that a great overall survival and recurrence rates were about-- I think there were a total five patients. And of those five patients, all of them were in Milan criteria by imaging at the time of transplant. But when they looked at the explant, which is one of the problems, is that we underestimate what we see on imaging. One had vascular invasion, macrovascular, which is a high risk of recurrence, and two of the five were outside the Milan criteria.

So, I think this was an important article because it showed, you know, what we've been thinking about. Can we be using more therapies to get people to transplant? There was a fear about rejection, which is why this wasn't used upfront. And people were accidentally getting transplants because they got immunotherapy, had a great response, and then people started saying, "Well, they had such a good response, why don't we transplant them?" And in this, they had seven people who rejected. One lost their graft and they did re-transplant that person. And the vast majority of those patients, six out of seven, had not had a washout period of greater than three months, which is kind of what people are saying, two to three half-lifes, which is about around three months.

So, I just think it shows the feasibility of doing this. We are certainly doing this at Northwestern. We have transplanted to date, I believe, it's close to six or seven patients who have been on immunotherapy and we have more who are on the list. So, we have embraced this idea of trying to get people to transplant. Some of the limitations are it was a short follow up. So, we'll have to see down the road, you know, is this therapy preventing recurrence in general or is it just kicking the can down the road and they're going to recur potentially later? The vast majority of people had viral hepatitis and we now know that we are seeing more alcohol and MASH. There is not a distinction in terms of immunotherapy versus one versus the other. However, I think as we get more data, it'll be important to see what we're more likely seeing in transplant now, which are those etiologies of steatosis.

Host: Great. And any comment on, you know, you talked about this washout period of ideally about three months or so. Obviously, when patients are listed for a transplant, they could get transplanted at any time. So, any thoughts or comments about the timing of, you know, when do we stop immunotherapy and say they're good to go? Do we always want to have that three-month period? Do we do it once the upgrade kicks in? Any comment on that?

Dr. Laura Kulik: Yeah. So, when you get the upgrade, once they've been downstaged, then we know that they have to wait six months. So, we kind of have a period of when we could stop it, keep them on for another couple cycles. They get to that three months before they're going to get their actual MELD upgrade, and then you could stop it. You know, some have argued this is also a period to see if there is any tumor growth when you take off the immunotherapy. But the rationale is not as strong for that because you get most of your bang for your buck with immunotherapy within the first two to four cycles. So, it's more to kind of have this washout. Because even though you may not be able to find the drug, you know, if you were to do a level, those lymphocytes are already turned on. So, they stay, remain turned on. And that's the risk of rejection.

So, we have had people who have decompensated and what we have done is gone to our multidisciplinary team and say, "This person has been off for this amount of time. Are we willing to move forward?" At least a month should be used. Two months is better, and three months is the most ideal.

Host: That's great. And Andres, let me get your comments or thoughts on this too. You know, she mentioned the increased risk of rejection potentially. So, anything special that we do here at Northwestern and anything you can comment on about our experience. I think Laura mentioned maybe six or seven patients that have gone through this process already.

Dr. Andres Duarte: So when we updated the protocol maybe about a year or year and a half ago, just to consider all of these patients that are going to have the immunotherapy, we actually reviewed the literature, Laura and I. And we saw that, you know, if it is within the first three weeks, it's almost universal that these people are going to have some form of rejection after transplant.

So, you know, in HCC, it's okay to wait those three months, but we also realize that for other type of tumors, for example, colorectal, colorectal cancer, maybe you don't have the luxury of waiting for three months. And that's why we basically have a mandatory four weeks. And then, with the understanding that we always want to wait for those 12 weeks or three months, as Laura is saying, to try to prevent the risk of rejection.

I know that we had one rejection, who by the way waited more than three months. He waited a while. The rejection was mild. And I think part of it is just because we started reducing the immunosuppression a little bit faster. So, I think the key in these patients, irrespective of the timeframe, of the precaution that we follow with the timeframe, is that you really have to keep the immunosuppression. We give a little bit of higher immunosuppression to these recipients. And you also have to really slow down whenever you want to go down to one medication or lower the dose of the second medication that we always give.

Host: Yeah. Great. Thanks. Very interesting and certainly expanding the options for patients nowadays with liver cancer. So, that's great. And on to you, Amanda. What article did you choose?

Dr. Amanda Cheung: So, the title of the article I chose was Low-to-Moderate Alcohol Consumption is Associated with Increased Fibrosis in Individuals with Metabolic Dysfunction-Associated Steatotic Liver Disease, published in the Journal of Hepatology this past December by the research group out of Valencia, Spain.

The reason I chose this study was mainly because it challenges what we maybe have historically told patients about what's a safe level of alcohol consumption. And because this question inevitably comes up by patients at least once, probably more in every single clinic about how much alcohol can I really consume, even if I don't have alcohol-associated liver disease. And then, also, it's just a very common question from referring providers about all what's the proper way to counsel patients.

So, it was a population-based cohort study based on two nationwide databases, one from the United States, NHANES, and one from Spain. The baseline population, which is the general population, was about 10,000 patients. The prevalence of MASLD or fatty liver disease is roughly 25-30% depending on the population. Now, we needed some data to base a study on, so they used transient elastography, so not every patient in the cohort had that. But ultimately, they had about 2200 patients in the cohort that they were able to study.

So, a couple of definitions. So, they used transient elastography, which we colloquially refer to as FibroScan. And they measured a controlled attenuation parameter to CAP score. Used a cutoff of 275 to define the presence of steatosis, and then deliver stiffness measurement also using the transient elastography test with a cutoff of 8 kilopascals as being clinically significant fibrosis or what they refer to as advanced disease.

Other the definitions that they defined was the amount of alcohol use. So, they actually created four different categories, very low alcohol use, which is close to none; low, moderate, or increased alcohol use. And they used increased alcohol use to basically correlate with the MetALD category.

So, MetALD, the newer term that-- I guess it's been over a year now-- that we've been using that's been supported by different societies is essentially just defined as somebody who has the right risk factors for MASLD, but also has excessive alcohol use As we define it. The society guidelines define it as 10 to 25 drinks a week on average for women, and 15 to 30 drinks on average per week for men. So, they looked at the numbers. And what was seen was that there's an independent association with diabetes, obesity, and amount of alcohol use with the amount of fibrosis. That's kind of obvious information, right? We know that already. But the novel thing about this study is what they found was that there's also a dose-dependent effect and a super additive effect between all these different variables.

So for instance, if you take a cohort of patients who all have one cardiometabolic risk factor, and you start to add on the amount of alcohol they drink, there's an exponential increase in the amount of fibrosis you're seeing. And similarly, if you take a cohort of patients who all drink five to nine drinks a week, and then you start adding cardiometabolic risk factors, 1, 2, 3, 4, 5, then it also starts to increase exponentially as well.

So, MetALD, which is the highest amount of alcohol use that was looked at in this study obviously has the highest risk of fibrosis development. But even in your low-to-moderate alcohol consumption groups, you also have a significant increase in the amount of fibrosis that was developing. So, it really challenges what we've historically told patients or historically even said ourselves, which is that low-to-moderate alcohol use may be even be beneficial in some literature way back in the past, but actually now maybe it's actually harmful. So for the clinician, the important thing for the clinician is to make sure that they're actually screening for alcohol use in all their patients, especially the ones who have cardiometabolic risk factors. And then, also using this information to counsel patients regarding how much alcohol really is or isn't safe to consume.

Host: Great. Thanks. And I know one of the things I mentioned, that article also is a comment about how a lot of MASLD patients will underestimate or not come forth with how much alcohol they actually drink. So in your practice, do you get phosphatidylethanol levels on your patients? Or how do you sort of probe them more deeply about how much alcohol they're drinking? The ANI score is also mentioned as something to help figure out how much alcohol might be playing a role. So, how do you use those things when you're seeing patients?

Dr. Amanda Cheung: Yeah. So, the best method, depending on who you ask for defining or to explore that without using any labs is the timeline follow back, which is a little bit arduous. But I essentially do something kind of like that and just say, you know, "In this past week, how many days did you drink? In the day that you drank, how much did you consume?" So, it gives you kind of a good idea, unless they just really won't pin it down. In that circumstance, so the phosphatidylethanol, which is a good marker of how much alcohol has been consumed in the past month, I don't check a PEth on everybody across the board, but it's usually if something in their laboratory results is really pointing towards alcohol. But if the consumption that they're reporting is discordant with it, then I will check a PEth and I let them know I'm checking, like, you know, "I just want to see how much alcohol is really on board in your system, how much of a role is it really playing in what's happening with your liver."

Host: That sounds good. And Laura, you know, we have this classification of steatotic liver disease from the AASLD. And, you know, on the website now, they've got this picture of this classification of MASLD and then alcohol. And then, in between it's the MetALD category. And then, there's a spectrum of how many grams per day a person might consume or grams per week. And I kind of struggle with that a little bit because when I ask my patients how much they drink, they don't come back to me and say, "I drink 30 grams a day." And likewise, when you ask patients how many drinks they have, you know, one drink is very different to different people. So, any sort of practical advice or pointers about how you inquire about alcohol use in your patients?

Dr. Laura Kulik: So, I first kind of tried to ask them, you know, and be very nonchalant, "Well, how much do you drink in a week?" You know? And then, when they're not saying anything, I'll be like, "Do you drink six beers? Do you drink a case? Do you drink a handle?" You know, you're throwing out these numbers, I think it makes them a little bit more comfortable to say how much they're really drinking. And it's important for them to know. You know, there's a lot of people who think, "Well, I've only drank beer my entire life," and they have cirrhosis.

Patients often think that you have to be drinking hard liquor in order to develop liver disease. So, I go through with them and sometimes I'll pull it up on the computer. There's lots of good pictures that your standard beer is the same as what you would get in a restaurant for wine, which I believe is five ounces and a standard shot, which I think is like one to 1.5 ounces. And each of those carries about 12 to 14 grams of alcohol. So, that becomes important when you're talking about, okay, a woman is not supposed to have more than one drink per day or seven drinks. And this is where you get these 20 to 30 per per day in terms of grams.

So, you have to kind of educate them on what each one is. And then, I think the really important is when they know that they have MASLD, they're kind of like, "Well, I have an explanation for my liver disease. And they kind of don't really take into account the alcohol." And this article that Amanda described, I think is really important because I've heard people say that if you have diabetes and you drink at all, because diabetes is your highest risk factor of developing chronic liver disease in MASLD, your risk of developing cirrhosis goes up by almost ninefold, and that's just with any alcohol. So, it kind of speaks to the point that Amanda was saying. So, really taking the time and talk to patients about this as well as the risk of cancers, dementia, heart disease, et cetera. When you start telling them those things, you start to see their eyes get a little bit big and maybe some understanding that, okay, this is detrimental.

Host: Yeah. I think when you get those patients that are sort of wishy-washy with how much they're drinking, a lot of times they'll just sort of say, "Okay, what do you drink and how do you buy it?" And I think that usually goes a long way, sort of cutting to the chase. Because once you hear people talking about buying a handle, you know, they're big drinkers. And just for perspective, you know, 1.75 liter container of alcohol contains about 40 standard drinks as well. So mentally, I sort of think about 40 ounces, even though it's not 40 ounces. But I sort of just try to make that mental tie in in my head between, you know, what a 1.75 liter thing of alcohol is. But yeah, patients are sort of all over the place sometimes in terms of what they're willing to admit to from alcohol consumption. But I think this is a great article for making us more aware about the importance of alcohol consumption in such a common disease, you know, like MASLD. So, it's great. So, Andres, let's turn to you now. What article do you have to share?

Dr. Andres Duarte: So, I'm going to talk about controversies regarding the use of albumin, and this was owned by Jonel Trebicka from University of Münster in Germany and Guadalupe Garcia-Tsao from Yale University. And this is published in Hepatology just January of this year. It's funny because it was accepted in May 2023. So, it took a while for it to make it to the press, but it's there and it's available.

And I chose this because I thought it was very practical. If you're a gastroenterologist, you're taking care of inpatients, I thought it was very practical for you to read this manuscript because I also believe, you know, kind of life divides the practice of hepatology, either you're an albumin lover or you're an albumin non-believer, right? And I think this manuscript is like everything in perspective. Like, when is it that is important for you to use albumin? That basically is only three indications, you know, SBP, which Sarang already mentioned when you have your patient with acute kidney injury and when you're doing large volume paracentesis, and one of those indications. But really, it's not that important. And for example, hepatic encephalopathy, you know, even though there is a recent meta-analysis saying that maybe it is important like these manuscripts just bust that along with, you know, your patient having outpatient albumin or your patient having hyponatremia, et cetera.

So, this is very clear about the three indications. And if you're a busy clinician and you don't have time to read this matter, just take Table 1 with you. Table 1, it's also beautifully written, basically summarizes the whole paper just there. And so, we attribute a lot of properties to albumin. And this goes with the albumin lovers where, you know, it's an antioxidant, anti-inflammatory, antithrombotic, et cetera.

Host: It is the evil humors.

Dr. Andres Duarte: Yes. But then, eventually, when you're tested in a clinical trial, it's not as important as it is. And I think that the two important concepts in the pathophysiology. The first one will be that you have to think about the effective arterial blood volume. The effective arterial blood volume is not how swollen your patient is. It's whatever is really going through the left ventricle to the rest of your body. And at that, in the underfilling theory of cirrhosis where all this vasodilatation in your vessels in the abdomen are kind of stealing some blood flow from your arteries, that creates this underfilling, that creates this lack of effective volume. And eventually, that activates the renin-angiotensin-aldosterone system. And that is what causes hypoperfusion and acute kidney injury. So, this is all about acute kidney injury, at least for the three indications, which goes into the real effective value of albumin, is its oncotic pressure.

And the second thing that I want to mention just before I go into the three indications is that we are also getting afraid about pulmonary edema because the more recent study, the CONFIRM trial, just showed a large frequency of pulmonary edema in the patients that were placed on terlipressin, 13.5% versus 5% just in the placebo. This is actually unique and the study was criticized because the other clinical trials, they either did not describe pulmonary edema, the SIMEU study, the Italian study or even the REVERSE study, the American by Tom Boyer, or they describe it at lower rates that were not really different between placebo and terlipressin.

So, we got to be careful about pulmonary edema. We got to make sure that our patients don't go on to develop it while on albumin. But keep in mind, great part of the pulmonary edema is most likely the albumin, not the terlipressin. And so, this paper is also clear about that and about being careful with the albumin management to prevent this complication.

So, indication number one is just post-paracentesis. The range is wide. You give 4 to 8 grams per liter of ascites that you pull out. And of course, when you put your instructions for your interventional radiologist, it's like, "Okay, how do I explain to my interventional radiologist?" So, something I stole from one of my colleagues is, and I've just been doing this for the last many years, I just do one bottle of 25 grams, 25% for every three liters that you remove. And you give that to your interventional radiologist or to your resident, whomever. And boy, it works really as a magic. So, that's the first one.

The second one, and very important, and this is one of the few manuscripts that actually review these evidence in the literature. The study that showed that the more than five liters is where albumin is helpful, did not include no-infusion for those less than five liters, which means that if you're draining less than five liters, it doesn't mean your patient will be okay off of albumin, because those patients actually receive some other thing in various clinical trials. So, this paper also kind of is specific about it is most likely preferable to give albumin even to those patients that are having paracentesis with less than five liters. And the patients that we see at Northwestern that are pretty sick, non-transplant candidates, I just do that. If they have refractory ascites, I just do that, even if they're draining only three or four liters.

So, the second thing is SBP. And Sarang already mentioned that, so I'm not going to get into that. But it decreases not only the risk of acute injury, but also improves the survival of this population. And the third one is acute kidney injury. And this is a combined, I guess, indication because, first you're going to be using your albumin to diagnose your type of AKI. So if you think about this effective arterial volume, the first thing that you're going to do is your albumin challenge. You're going to give it 1 gram per kilo per day. This has to be done for at least a day, ideally two days. In the older literature, it was even up to three days. And you're going to do this just to make sure that your patient, that this is not a pre-renal acute kidney. And if it is not, and you're going to start your patient on terlipressin, you got to continue for an extra day with 1 gram per kilo. And then, you reduce dose to 20, 40 grams per day. And I got to be clear that it seems like Jonel Trebicka wrote a paper because he's actually using the indication from Europe, not the ones from the United States, because we don't have 20 and 40 grams here. So, you know, when I read on a paper 20 grams, I just think of 25 grams. And when I read 40, I just think of 50 grams. I just automatically make the conversion. If you think about skinny French versus, you know, less skinny Americans, I also think it makes sense just to do this type of conversion.

So yeah, basically that's what the manuscript was about. I really would encourage people listening to the podcast to take a look at it. And again, if you don't have time, just take Table 1 with you.

Host: Yeah, it was a great article and really summarized a lot of the information out there about albumin. Let me ask you about the whole 1.5 grams per kilogram on day one and 1 gram per kilogram on day three. Twenty-five years on, we keep doing this. Got a little adventurous at times and I've admittedly done 1.5 grams per kilogram on day one, sometimes a gram per kilogram on day two. Is that okay?

Dr. Andres Duarte: I think it is. And I also have to say that this is the first paper that I read that kind of challenges that. Because with our residents and our fellows, like many times people can get very fixated on this dose. I mean, here, it's all about the that left ventricle needs to have enough blood volume to the kidney. So, you're just helping that, if you're doing it by following the SBP formula developed in the '90s, or if you want to do it, for example, with the AKI formula. And they actually say, again, this is the first manuscript that I see recommending that if you do like your AKI formula, 1 gram per kilo for three days, that's perfect, or two days.

Host: Okay. Whew. I feel better. Sarang, let me get your thoughts on albumin. Obviously, there's 5% albumin and 25% albumin. So, you know, when you're giving your patients albumin, sort of what are your thoughts about when you choose 5% versus 25%? Or do you ever mix the two together? Or how do you do that?

Dr. Sarang Thaker: So, it depends on what you're using it for, right? So for AKI, for instance, I know they like to use initially 5%. You just get a little bit worried about flooding them, right? If they're not urinating, pulmonary edema risk. So, sometimes I'll start with five, maybe mix and match dealer's choice as long as you get, you know, enough grams to them. Presumably, there's enough, you know, filling and you've raised their effective arterial blood. If they already have massive ascites, getting paracentesis, 25% makes a lot more sense rather than helping them reaccumulate ascites. So, you know, it kind of just depends on you're trying to resuscitate volume or just get more forward flow to those kidneys.

Host: Because I mean, 50 grams of 5% is basically a liter of fluid. So, you know, depending on how much albumin you're trying to give the patient, sometimes that's a lot of volume like you mentioned. So, great.

Dr. Andres Duarte: And a lot of sodium, right? It will be 153 milliequivalents of sodium, which is past the daily limitation that we want our patients to follow with the diet.

Host: Right. Great point. Well, that wraps up our discussion today of favorite articles from the past year and definitely appreciate all you guys thoughtfully selecting articles to share today. So, hopefully, some nice new information about HCC and the use of immunotherapy for being able to downstage some of our more advanced patients and potentially get them to transplant. Some little pearls of wisdom about albumin and paracentesis on our inpatient management. And then, also from Amanda getting us to think more about alcohol use in our MASLD patients as well.

To refer a patient or to learn more about Northwestern Medicine, visit our website at breakthroughsforphysicians.nM.org. Also, please join us in the fall. We'll host another round table discussion for updates and findings from the AACD Annual Liver meeting in November.

This concludes our podcast today of Better Edge, a Northwestern Medicine Podcast for physicians. I'm Dr. Sean Koppe. And thank you for joining us today.