C (2:07)

Yeah, I'm Happy to. So we had a conversation with Dr. Matherly. He's an associate professor of medicine at Virginia Commonwealth University. He is also the program director for the transplant Hepatology fellowship at vcu, where his clinical interests include decompensated cirrhosis, liver transplant, and hcc. Tonight, he teaches us about the initial evaluation and workup of cirrhosis, including what labs to send, what to look for as far as fibrosis findings, additional imaging to order, and then next steps for evaluating for decompensation, what treatments and management guidance he has for different decompensation and cirrhosis, and then really when to think about a transplant, including making sure that we're sending patients early enough based on their clinical factors and their labs as well. So without further ado, let's get to it.

A (3:02)

And a reminder that this and most episodes will be available for CME credit for all health professionals for VCU Health at Curbsiders. VCU Health. Welcome back, Scott. We've been talking for a while. It's great to see you again. Longtime listeners will know that we've talked to you about the liver before, but we're grateful to have you back to talk a little bit more about liver and cirrhosis and how to identify and manage it. But before we get there, as we always do, we like to ask a few questions just to get to know you a little bit better. And I wonder if you could update us on any hobbies that you've developed or any changes that have happened since the last time we talked to you, which I think we figured out was like, God, six years ago, something like that. So what have you been up to?

B (3:39)

It's pretty wild. And thanks for having me back. I'm. I'm really excited to be here. I, I tell you, one thing that I've done is I've had more kids. So there's that. I think I've had two more kids since I last.

A (3:52)

Oh, my gosh.

B (3:53)

Talked on the Curbsiders episode. Hopefully I'm done. I, I turned 50 this year, and I, I think it's time to stop having children. But this, the other thing that I've gotten into is competitive powerlifting. Believe it or not. This. This is my midlife crisis. I, I could have bought a. I could have bought myself a convertible or something like that, but instead I got a minivan and I started doing competitive powerlifting.

C (4:20)

That's impressive.

A (4:22)

What does that look like for you? Like, are, are you. Do you, do you tour around with it? Like, I guess when you say competitive, tell Me about the competitive part. Like what? How many competitions are you doing? Who. What type of people are you competing against? What does that look like?

B (4:32)

Well, it's not pretty because I have to wear a onesie, a singlet as it's called in the game. But yeah, no, I just signed up for competitions, trying to do about two a year. I'm only competing against myself and that's sort of my mindset. But at the same time it's also the reality because I'm a 50 year old and not many 50 year olds do powerlifting. So I did win a gold medal at my first competition, which I was very excited about, but there was no competition in my age range, so I was the only participant in my age. But I did win a gold medal, so I'm very proud of that.

A (5:14)

Yeah, it was yours to lose. Really?

C (5:18)

Yeah, you can leave that part out. No one has to know. Another question we like to ask is something a favorite failure of yours and what you learned from can or cannot be related to medicine too? It's up to you?

B (5:32)

No, I think this is an important one. And I'm not sure if I talked about this on my previous episodes, but my favorite failure remains the fact that I didn't match into GI Fellowship the first time. When I tried to match, I thought of myself as a hotshot internal medicine resident. I was at a big program and I felt like I was going to get into whatever program I wanted and I didn't match. That is ultimately how I ended up where I am now at VCU as I scrambled into a position. And that was some years ago. At the time, one of the most devastating things that's ever happened to me in my life. And I still think about that. And from that failure has come my entire career and my passion, what I do, my niche, Everything has sort of sprung from that failure. So that remains my favorite failure. So I'm not sure if I talked about that like previously. But you know, if you're out there and you're trying to get into a competitive fellowship and it doesn't happen the first time, you can really turn that around and make it work in your favor. So I always think about. I still think about that. And I've been on faculty now for like 11 years and I've moved up the chain. I'm an associate professor, but I would have never been at VCU had that not happened to me. So I still think about that.

A (7:04)

It's such a great point. I can't remember if I ever said this in the show or not. But if I had to pick one of my own favorite failures, it would actually be the time I dropped out of college. The first time through I was majoring in psychology and I just didn't go to classes. And I just think how different my life would have looked had I managed to limp along and just stay in and just pick a major that I could tolerate and sort of finish with something that I was kind of half satisfied with. I would be in a completely different place now. As opposed to having that huge failure and a chance to sort of recalibrate and to go, I want to do with myself like some 10 years later. So it's. Yeah, it's. I love that story.

C (7:35)

Yeah. Certainly nice to hear. I think more stories like that, particularly when people are going through the process, it's like, you know, these things happen to a lot of people. It's not what you read everywhere, you know.

A (7:53)

Right. And it may feel bad in the moment you ultimately end up where you belong. So that's terrific. All right, well, with that feel good story, why don't we transition to a case from cash like hospital. Elena, I think you are going to tell us about. I believe the name is Paulina.

C (8:05)

Yeah, you see what I did there?

A (8:08)

Right?

B (8:09)

Clever.

C (8:10)

All right, so first case or the case really. Paulina is a 57 year old with a history of obesity. She's had a prior Roux en y gastric bypass hypertension and she did have a history of alcohol use disorder about five or 10 years ago who recently had a CT of her abdomen and pelvis completed for evaluation of abdominal pain in an emergency department. She was found to have evidence of hepatic nodularity and swenomegaly on that imaging. And now she's coming for a follow up. So seeing this case with just imaging findings of this nodularity in splenomegaly, what would what additional evaluation would you send for the etiology and complications of cirrhosis?

B (8:57)

Well, this is a great case and I think just looking at the initial stem, the history of the patient should give you some clues like right away what you might be dealing with. So the history of obesity and the Roux and why gastric bypass should raise your suspicion for like a metabolic fatty liver disease or metabolic steatotic liver disease or something along that front. But also the presence of a Roux en ligastric bypass with alcohol use should also sort of pique your curiosity because we know that people with Roux en y gastric bypasses are more prone to alcohol related liver Damage, they have higher peaks of alcohol when they drink. The alcohol stays in their system longer because they lack that first pass metabolism of the gastric, you know, alcohol dehydrogenase. So that's. It's always a huge problem when patients get, have a ruined Y gastric bypass and then drink alcohol afterwards. So what labs would we send? You know, we're just going to do the sort of basic workup. We have a, we have a working idea of what the patient may have, why they might have cirrhosis. And so I would certainly do your basic, you know, viral hepatitis serologies. If they haven't been done, you're going to check your vitamin, your hepatitis B, your hepatitis C, probably just send antibodies, hepatitis C antibodies, hepatitis B surface antigen, and maybe a core antibody to see if they've ever previously been exposed. I send metabolic, like congenital metabolic disorder workups like Alpha1 Antitrypsin, I think is a very important one to send ferritin transferrin saturation and plus or minus ceruloplasmin. I think ceruloplasmin workup for Wilson disease is a lab test that's a little bit fraught with diagnostic confusion. So you have to be able to interpret that with a great deal of context. If you do send it and then autoimmune markers, you know, a female patient, you're gonna think autoimmune disease of the liver. So ana a smooth muscle antibody plus or minus a mitochondrial, depending on what their overall labs kind of look like. I would also kind of caution you to look at the imaging yourself. You know, I've long ago become fairly cynical and skeptical about radiology diagnoses of cirrhosis. I would pull it up myself, look at the liver, measure the portal vein, look at the spleen, see if there's any other signs of cirrhosis on that imaging. Some of them are cut and dry and they're clearly cirrhosis. Some of them are just nodular liver, slightly nodular livers. And it's not uncommon for people to get labeled cirrhosis that don't actually have it. So that's the other piece that I would throw out there.

A (11:51)

Yeah. So let's give you some labs to work with and then we can sort of talk more about where to go from here. So for Paulina here, her lab show an AST of 22, an ALT of 32, ALKLOS of 125. Her total bilia is normal. Her platelets are 143. INR is 1.1, albumin is 4.2. She has a hemoglobin that is normal, her creatinine is normal, she has sodium in the normal range. So so far, you know, let's say we're still waiting for some of these sort of fancy pants, especially testicle Mac, but maybe let's even assume that most of them have come back sort of unremarkable so that there's no evidence of autoimmune disease or autoimmune hepatitis or anything like that, which I imagine is what the workup looks like much of the time in circumstances like this. So where, where to go from here? Do we need additional imaging? You mentioned you don't trust the read necessarily. Is this someone that you would send for an additional ultrasound or sort of what kind of, what additional diagnostic workup is needed?

B (12:40)

Yeah, I mean this is a great example because this is not uncommon for what you're going to see. Right. If you look at her labs, the alt is 32. So for someone born female or alt should be an upper limit of an alt should be around 25. If you're seeing alts above 25, that is abnormal. Your computer EMR is not going to say it's abnormal. It's going to show anything below 40 something as being normal. But the reality of the situation is we know that those born female, if the alt is over 25 regularly, that's associated with liver related morbidity and mortality. So 25 for us is really a normal. It's more like 30 for, for those born male, you know, but so a 32 I would consider a minimal elevation. The AST to ALT ratio is not what we would typically associate with cirrhosis. You know, usually we're going to see an AST greater than alt. Classically with cirrhosis though, that's not always going to be the case. Alkaline phosphatase, minimally, minimally abnormal is not, not much you, not much hay you can make with that. The platelet. You know, my eyes always go to platelet counts and I think the platelet counts are an important thing to kind of look at when you're considering whether somebody has advanced hepatic fibrosis. This platelet count is a little bit on the low side. When I see lower platelet counts that, that automatically makes me more suspicious that we might be dealing with a cirrhosis type situation. The one thing you can really do with this information, and one thing I would advocate that people kind of get in the habit of doing is maybe do a simple calculation based off of these labs and there's a couple of different ones out there. But my bias is to use what's called the fib4. The fib4 is a very, very simple calculation using the AST, ALT, platelet count, and age. The fib4 is a very useful tool in determining risk of fibrosis. Okay. And if, if a fib 4 is low, then that is suggestive that a patient does not have advanced fiber fibrosis. But much like many non invasive markers of hepatic fibrosis, if it's not low, it becomes increasingly less useful. And for me, I use it really as a negative predictive test. I use this as a test to tell me should I not be worried or should I be worried? And a FIB4 less than 1.45 for viral hepatitis or 1.3 for metabolic steatotic liver disease is associated with F0F1, the F1 fibrosis. So early to know hepatic fibrosis. I did a calculation for our patient here at Cash Lac and her fib 4 comes back as 1.55. So 1.55 is above those cutoffs. It's one point, you know, 1.3 to 1.45. Anything above that you need to be a little bit concerned about. Now hers comes back at 1.55, and that would suggest that further investigation would be recommended.

A (15:46)

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B (19:15)

The reason I sort of advocate this is very easy to do in clinic, right? If you, if you have a patient say that you had an ultrasound and it shows they have a fatty liver and you've got their liver enzymes and you've got a cbc, you can do this calculation very easily. And if it's normal, then you're reassured. If it's not normal, then you probably need to be thinking, what's the next step? What's the next step in imaging? Where should I do? If you have vibration controlled transient elastography at your disposal, that would be a great next step for, for someone like this. You send them there, you put them through what I call the thumper test, little ultrasound based tests. You thump them a few times and it's gonna tell you basically the stiffness of the liver. And it's also gonna give you an idea of the amount of fat in there, though you have to interpret that with some caution. Vibration control transient elastography is a great tool to kind of tell you again, I consider this a negative predictive tool, but there is some utility in it that we can talk about a little bit later. A more sensitive tool that's also more expensive and more difficult to do is Mr. Elastography. So you can, you can do magnetic resonance elastography where you put the patient in an MRI machine. They get this very funny little paddle put on their abdomen and it vibrates their abdomen as they're having the MRI done and it gives you kind of a global liver stiffness that's more sensitive. It's better than vibration controlled transient elastography, which is a bedside ultrasound based test, but it's also expensive. It involves usually over an hour in the MRI machine. And in my experience I have a little bit difficult time either getting insurances to pay for that or getting patients to lay in a MRI tube for an hour and 15 minutes. But those are the options that are kind of available to you for additional imaging. I would say that this is an early inflection point if you're a primary care doctor or an internal medicine doctor and you don't know where to go with this information. This is an easy referral to a.

A (21:18)

Hepatologist point you may have answered. My follow up question is how reassured by a low fib 4 should it be so, for instance, for a patient like this who has evidence of nodular imaging and say the lab values are slightly different, the platelets are higher, or there was less, the transaminases are a little bit lower, and the fib4 comes back okay. If anything, can you be reassured by that and be like, well, I guess the imaging is kind of off or what? I guess. How does that alter your workup if the fib4 is okay, but there's still potentially radiographic evidence of nodularity in the liver?

B (21:50)

Yeah, no, that's a great question. In my opinion and in my practice, I think if you have conflicting data, you need a tiebreaker of some sort. I don't consider the fib4 to be that powerful of a tool to overrule a CT finding of a nodular liver and splenomega with a low plate like that. I would not, I would not use that and just say, oh, there's nothing to worry about here. I would probably then proceed to a third test. And the third test for me would either be a vibration controlled transient elastography or a liver biopsy. And to be honest with you, that's the discussion I would have with my patient. You know, I say we can do this fairly easy and non invasive test which may or may not answer the question, or we could go with the gold standard, which is a liver biopsy.

C (22:37)

Can. I think you kind of mentioned this before, but how much weight do you put into the splenomegaly? And then you mentioned measuring the portal vein. What are you looking for there?

B (22:48)

Basically, as you develop portal hypertension, your portal vein enlarges and I don't think it can be diagnostic of its own. But as you mentioned, the splenomegaly is a concerning finding, but it's also a non specific finding. I mean, it's not pathognomonic of cirrhosis to have an enlarged spleen. There are other things that can cause an enlarged spleen. So I would say that if I had an enlarged spleen with a 0.8 centimeter portal vein, which is a normal sized portal vein, I would be wondering if there was something else going on. Whereas if I have enlarged spleen with a 2 centimeter portal vein and a nodular liver that's more indicative of portal hypertension.

A (23:30)

And I'm not sure if this is fair to ask, but let's say this person is in the exam room in front of you and this is the data that you have so far. I guess I do like to ask about physical examination and certainly I'm not asking for what the 97 pathogenomic findings associated with cirrhosis or however many there are, but what are the things that you would focus on in an examination for a patient like this?

B (23:49)

Yeah, I mean, I do a pretty standard evaluation on everybody in my physical exam. And I, you know, I. I was taught in residency. I always start with the hands. You know, I look at the hands. I'm looking for, you know, there's seven hand findings of cirrhosis. You know, I think we probably talked about on. On prior episodes, but, you know, I look at their nails. Look for Terry's nails. Palma erythema. Those are the sort of big ones. Spiders. You know, if patients got spider angiomata on their upper extremities, upper chest, that's very indicative of cirrhosis in this sort of standpoint. In this sort of example, I'm assuming that they're not blatantly jaundiced or have other sort of sort of big physical examples. Oh, they also have 10 societies. But, you know, so I think. I think those are the things that would maybe kind of clue me. And if I'm seeing spider angiomata, palma erythema, Terry's nails, these. These are all sort of other sort of auxiliary physical exam findings that may give me a clue that we actually do have cirrhosis going on.

C (24:59)

And not to belabor this CT that she had, but Ms. Paulina, she also had some small varices on her CT that were noted. Should she be started on a beta blocker now or should she undergo an EGD for variceal screening?

B (25:16)

This is a good question and kind of an interesting one. And I would say that cirrhosis management is probably undergoing an evolution as we speak because there is a movement towards earlier use of beta blockers. There's a movement towards using beta blockers without endoscopy, especially utilizing liver stiffness and platelet counts. And I suppose we can talk about that sort of stuff more. But in my humble opinion, I would not typically start a beta blocker without doing an upper endoscopy in most patients. If I feel like I simply can't get the patient in for an endoscopy, like it's an impossibility for whatever reason. And I have a high concern, like on the CT scan, I'm actually seeing varices, that sort of thing, then I may. I may start a beta blocker, and that has rarely happened from time to time. But I think that there's some value to having an upper endoscopy I think there's a value to having a baseline and know what you're dealing with. Right. So with the upper endoscopy, you know if they have esophageal varices or not. CAT scans, even if they're showing varices, they're frequently showing peri. Esophageal varices that are not necessarily in the lumen don't necessarily increase the patient's risk of bleeding. You're not going to know if the patient has gastric varices or certainly unusual gastric varices that could require completely different modes of therapy. Beta blockers don't necessarily prevent bleeding from gastric varices. So I think of a patient as clinically significant portal hypertension. The gold standard is to do an upper endoscopy. And I think that that is still where I would plant my flag at this point.

A (27:00)

And we were talking a little bit before we got started. I think even since I've started practicing medicine, the beta blockers that we use for varices have changed over time. So can you sort of talk about what your first line choice would be and what the evidence is to support that?

B (27:13)

Yeah, this is something that's definitely evolved over the last few years. And the big evolution is the sort of development of more and better evidence that carvedilol is potentially superior to the non selective beta blockers that we've traditionally use. So we've traditionally used natall and propranolol for patients with clinically significant portal hypertension and varices to prevent variceal bleeding. The most recent guidance from the American association for the Study of Liver Disease actually now recommend says that carvedilol is the preferred beta blocker in portal hypertension. And there's a couple of reasons for that. With the non selective beta blockers, you're mostly working with beta 1 and beta 2 blockade to decrease cardiac output and to cause splanchnic vasoconstriction due to unopposed alpha in the mesentery. Carvedilol has that extra sort of alpha antagonism. Right. That actually works in the liver to increase vasodilatation of the vascular bed of the liver. And as a result it has a more profound portal vein portal pressure reduction than the non selective beta blockers propranolol and Natalo. And this has clearly been shown, it's been shown in head to head trials with the non selective beta blockers versus Carvedilol. We know that carvedilol lowers portal pressures more. There's also some studies that have come out. There's been two or three of them at this point, showing that patients on carvedilolol, when you compare with clinically significant portal hypertension, tend to do better than patients on other non selective beta blockers. The Prudeschi trial a few years ago showed decreases in decompensation on carvedilol, decrease that was primarily driven by a decrease in ascites formation. So I would say that carvedilol is really starting to push ahead as the sort of preferred beta blocker for these folks to the point that there, there is a movement. And some people are even starting folks on beta blockers, you know, before they even necessarily develop varices, if they feel like that they've got significant portal hypertension or they're treating them with small varices, which was not necessarily the practice pattern. We would typically treat someone with large varices with a beta blocker or someone that had bled from varices previously.

A (29:37)

Right.

B (29:38)

The other thing that's kind of nice about carvedilol is its dosing. Its dosing is a little bit simpler than the other non selective beta blockers. And I see this as something that people get confused about out there. You know, with the non selected beta blockers, natolol and propranolol, you're gonna dose those guys by pulse. So you're trying to get the pulse down, right? And you give them, you start em on 20 or whatever you're gonna start em on, and then you just keep increasing the dose until you get their pulse down like 25%, usually down into the 50 to 60 range. That's kind of what we try to achieve, which involves a lot of titration and a lot of visits and, you know, a lot of annoyance. But Carvedilol, you literally start at 6.25 milligrams once a day. And then if they're tolerating that after a few days, you can increase it to 6.25 twice a day. And that's your goal. Okay? That's what you try to achieve. You try to achieve 6.25 twice a day. If not, then 6.25 once a day, and you can go as high as 12.5 milligrams twice a day. Say if it's somebody that's hypertensive or they can really handle it, but you don't worry about the pulse, and you want to kind of max it out at 25 milligrams a day. For, for most cirrhotic type patients, when do you want to stop it? When their systolic blood pressure is less than 90. So that's the only Thing that, like, non hepatologists tend to struggle with. They're like, I'm putting someone whose blood pressure is 102systolic every time I check it on 6.25 bid of carvedilol. Yeah, we do it. And we're usually pretty happy if their systolic blood pressures, you know, hanging above 90. So that's kind of our go typically. So, yeah, I would say definitely evolution. Carvedilol is definitely starting to push ahead. I. I know in my practice, it. It's become the, the dominant beta blocker that I use.

A (31:30)

It feels very much like the, the old, the old days of heart failure where you're just titrating blood pressure medications to near syncope, and then you can back off a little bit. So I'm, I'm glad we've. We've become slightly less barbaric than that.

C (31:40)

Come along.

A (31:41)

And this is. I just, I just for clarification, I just want to make sure I'm understanding this is the immediate release Carbatallol that is still dosed once per day and then can be increased twice a day. Is that correct?

B (31:50)

Yes.

A (31:51)

Okay.

C (31:52)

Yeah. And just as a review, too. So if. I know in this specific case, we had seen some small varices on a ct, but who are you screening for varices following a diagnosis of cirrhosis?

B (32:04)

Yeah, so that's a great question as well. I mean, in the old days, we would just screen everybody for varices. If you have a diagnosis of cirrhosis, you would just have an upper endoscopy. There's some movement out there to only look at folks who have high risk sort of features. The beveno criteria, depending on what their liver stiffness is and their platelet count, you can determine what their risk for having varices is. But I still think if you think if the patient has cirrhosis, they need an upper endoscopy, and that's who we screen pretty much anyone with cirrhosis.

A (32:42)

All right, this is helpful. And Scott, while we're sort of. Before we have Paulina to completely decompensate and sort of talk about what to do with that and what things to look out for, let's say before we get to that point, you're meeting her in the office for the first time, could you sort of talk us through your script? When you're talking to patients with a new diagnosis of cirrhosis in terms of what's important in terms of diet and sort of hepato protection and behaviors to avoid or behaviors to engage in just your General counseling for patients with this new diagnosis.

B (33:09)

Yeah, no, I'm, I'm glad you asked that. I tell you, a new, new visit for me for a patient with cirrhosis is, is a long visit. I, Yeah, I, I don't know how you could fit this into like a, you know, 20 minute clinic slot. And sometimes my clinics go quite over. I, I had a new patient, you know, in the last few days, and I literally just sit and talk to them from beginning, I like to educate them about their disease because I, I find that people that know what's going on inside of them are more invested in, like, doing what they need to do to stay safe. So I spend a lot of education, I spend a lot of time just educating them because a lot of people come to me scared. A lot of people hear cirrhosis, they think a death sentence. I've heard, I've heard that many times. Most people that hear cirrhosis out in the community, there's a stigma attached to it that they associate. Everyone thinks I have, it's alcohol. I don't understand. I don't drink alcohol. So, yeah, I spend a lot of time educating them. I kind of tell them what cirrhosis is, what my, my sort of thought of what cirrhosis is, kind of the things that cause cirrhosis and then the complications of cirrhosis. And then I always give them my sort of little, little spiel, if you will, about, you know, what we can do to keep them safe with cirrhosis. You know, I've always, you know, have this thing that I always tell everybody that cirrhosis can kill you in four ways. And if we keep you from dying of these four things, then you won't die of cirrhosis and we don't need to worry about it. So that's kind of what I talk about. So it's a lot of education in my clinic visits that literally starts with, this is the liver, this is where the liver lives, this is what the liver does. And by the end, I've educated them about what portal hypertension is, why we need to do an upper endoscopy, why they're at risk for liver cancer.

A (35:09)

Why.

B (35:10)

We need to eat a certain way and do certain things. Dietary counseling. One of my big concerns with cirrhosis, and actually the fourth way that I tell people that cirrhosis can kill you is with malnutrition and sarcopenia, which is a huge concern of mine with my patients, especially after they've decompensated. But I am usually very pro Calories and pro protein for my patients. My mantra for patients with liver disease is if you eat less than half of a full size meal for any reason, I want you to take a protein shake or a supplement to make up for that loss of calories. And I say if that means you take one protein shake a day, so be it. If that means you take three protein shakes a day, so be it. But if our folks don't do this, especially if they have ascites, the, the muscle loss that they get, the sarcopenia that they develop is dramatic. It's very fast. They will literally wither away right, right in front of you. The other big, big thing that I typically recommend them to do is to have a big snack at bedtime. You know, the classic prototypical snack that I recommend is an apple with peanut butter. I mean, that's sort of the classic snack. Complex carbohydrates, fat and protein gives them a little bit of released calories because we know that the longer they go without eating, the prolonged fast periods is really when they get into trouble with muscle loss. That's really when they start to, to lose their muscle mass. So if we can limit those MPO periods, it's beneficial and this sort of translates into the hospital as well and some, something that you're taking care of. Cirrhotic patients on the inpatient world try to limit their NPO periods. It's really difficult. We've got to like, you're going to do a colonoscopy on them, you know, two days, whatever. Like having them MPO for like 20 hours is actually probably harming them pretty significantly. So just always think about that. I don't know how deep you want to go down the rabbit hole of diet, but you know, we can, we can talk about salt, salt restriction. I do recommend that my folks be mindful about sodium restriction. I am not strict about a 2 gram sodium diet. You know, I just empowered them. I said, look, it's basic chemistry. It's osmosis. The more salt you eat, the more fluid you're going to hold on to. You know, if I eat too much salt, my socks make a dent and, and I pee it all out the next day. I said, if you eat too much salt, you're going to dump it in your belly. So I'd say just try not to eat too much salt. The more salt you eat, you can defeat your diuretics. But we know that when we radically restrict sodium in folks, when we really drop them down to a 2,000 milligram, a day sodium diet. We restrict their caloric intake as well, and sometimes Fairly dramatically, like 20, 25% reduction in calories. And again, you're going to run into that sarcopenia frailty, debility problem in your cirrhotic patients. So for me, it's always a trade off. Do I want them to have a little extra fluid or ascites, or do I want them to have sarcopenia?

A (38:09)

That was the exact point I was going to make, is to limit someone to 2 grams of sodium and then tell them to eat a bunch of calories and protein. It's just you're, you're making food as unenjoyable as humanly possible.

C (38:18)

Yeah, I think that's a good reminder and I do think it'd be helpful. Could you describe that? I know you talked about sarcopenia as one of the ways you could die from cirrhosis, but what are the other three ways that you discuss?

B (38:31)

Yeah, now this is like colossally simplified, right? But I do find that this is useful for patients to kind of give them a concept of what's going on them and what we need to be on guard for. Okay. And my four ways that cirrhosis will kill you that I talk to all patients about. Number one is liver failure. Okay? And the way we're going to avoid liver failure killing you is we're going to identify what's causing this. We're going to send those tests we talked about, we're going to identify what's causing your liver disease, and we're going to see if we can do something about it. Okay? If it's alcohol, we're going to stay away from alcohol. If it's viral hepatitis, maybe we'll treat your hepatitis C. If it's fatty liver disease, we're going to do some mindful changes in your diet and see if we can lose a few pounds. Right? Because we know that weight loss is very, very beneficial for metabolic, steatotic liver disease. And if we do those sort of things and your liver disease does progress, then we'll talk about a liver transplantation, because ultimately that's how I'm going to keep you from dying of liver failure. If we can shut off the damage to your liver, your liver can often recover itself and sometimes fair dramatically, you know. Whereas if we are unable to cut off that damage or if there's too much damage done, that's when we'll talk to you about a liver transplant. And so the second way that cirrhosis can kill you is with bleeding and bleeding from varices in particular, you know, I tell them about portal hypertension. I tell them about how the gut, by how the liver drains the entire gut or how the liver accumulates the blood from the entire gut and how they can get these swollen blood vessels in the lower esophagus or upper stomach that we need to look for, for. And if you have them, we have to treat them. I tell them the third way that cirrhosis can kill you is with liver cancer. All right? That it's. Your risk of liver cancer is somewhere in the neighborhood of 3 to 5% per year, which translates into about one person out of 20 who has cirrhosis will get liver cancer each year. If I catch it when it's small, I can cure it. You know, if I catch it when it's 10cm, you usually have about a year to live. Okay? And we need to catch it when it's small. It's very, very important. And that's why we're going to need to do scans on you every six months. And that's why we're going to need to continue to do that for the rest of your life unless you get a liver transplant. And that's why, if you move to Kentucky in a year, you need to remember this and get yourself an appointment and make sure you continue to get your imaging every six months. So I sort of empower them on that front. And then the fourth way the cirrhosis can kill you is with malnutrition and infection. Okay? And this is. I say it's predominantly a problem in people that have ascites or fluid in their belly because they don't eat well, they become sarcophagus penic. They progressively lose their muscle mass and ultimately infection, such as SBP and stuff come into play, and it causes them to die. Now, you know, if you're a real cirrhosis expert, you would probably take issue with this and you say, oh, there's a bunch of other place ways you can die of cirrhosis. And yeah, that's probably correct, but I don't think that there's like, a tremendous utility in like, scaring the patient half to death. I do this mostly out of pragmatism because it gets them to understand why we're doing an upper endoscopy on them, why we're doing scans every six months, why I need them to eat well, why I need them to take protein, and, you know, you know, these sort of why I'm asking them not to drink alcohol, you know, so that's why I find that this framework, at least as I as it stands right now, is useful for.

A (41:54)

This episode is brought to you by Rocket Money folks. You know how it is. You'll sign up for some sort of subscription service. You forget about it after the trial period ends, and then you're charged for it, and then you're charged the next month and the month after that and the month after that. And you have the subscription that is there, but you're just not using it. 85% of people have at least one paid subscription that goes unused each month. Thanks to Rocket Money, you can see all of your subscriptions in one place and cancel the ones you're not using anymore. And now you're saving more money. Rocket Money is a personal finance app that helps find and cancel your unwanted subscriptions, monitors your spending, and helps lower your bills so you can grow your savings. Rocket Money will even try to negotiate lower bills for you. They can automatically scan your bills to find opportunities to save, and then you can ask them to negotiate for you. They'll deal with customer service so you don't have to. Rocket Money has over 5 million users and has saved a total of $500 million in canceled subscriptions, saving members up to $740 a year when using all of the app's premium features. Cancel your unwanted subscriptions and reach your financial goals faster with Rocket Money. Go to RocketMoney.com curb today. That's RocketMoney.com curb RocketMoney.com curb. That's really helpful. And I think before we make Paulina even sicker, I did want to ask for specific medication, counseling, if that's not too much to ask for in terms of meds to avoid or things to be mindful of. Can you sort of talk about your general spiel for that, too? I feel like it never hurts to hear that one more time from a primary care standpoint.

B (43:25)

Yeah. And it's, it's kind of surprising to people in general. And I, I see this literally coming out of the, you know, patients, primary cares and stuff like that. A big thing is pain. You know, I have a headache. What can I, you know, I can't take Tylenol. What can I take? You know, I have, you know, my, my joints hurt. My doctor says I can't take Tylenol anymore. And that, you know, one of the biggest. That's the biggest misperception for me because you can take Tylenol. Okay. And that's what I always. I'm sorry, Acetaminophen, you know, you can take Acetaminophen Right. So acetaminophen is a dose related liver toxin. It causes liver toxicity without a doubt at large doses. Right. But if you don't exceed those thresholds, then it's actually the safest thing that you can take for a liver. It's what we tell people on our transplant list to take when they have a headache. Our rule of thumb with acetaminophen is just don't take more than four extra strength acetaminophen a day. All right. And 2,000 milligrams a day, you stay below that, you're perfectly safe. Statins are an interesting creature. They always get discontinued by primary care doctors. I would say that most hepatologists are pretty okay with statins in general, especially for metabolic steatotic liver disease. I don't mind using them. I don't typically start them when the patient is decompensated, like is really sick. Most decompensated folks have pretty low cholesterol panels in general anyway. But I would say that statins, especially in com, I hate to see statins discontinued in compensated fatty liver disease patients. And I see it happen again and again and again. Those drugs are probably beneficial in cirrhosis, almost certainly beneficial in fatty liver disease, and the risk of liver toxicity is quite small. The thing that we see increased rates of as they become more decompensated is the muscle toxicity with statins. So that's what you have to be kind of aware of. Otherwise, medication wise, I try to get them to stay away from herbal supplements. People love to take liver cleanses and I hear them advertised on the radio. It drives me absolutely batty. And so I usually try to keep them away from that. Just not a lot of herbs and minerals and supplements. Just try to take a basic multivitamin and um, and let the liver be the cleanse because it doesn't need any help.

C (45:50)

So let's kind of recap how we got here now. So initially a diagnosis of cirrhosis, you'll send the evaluation work up, including evaluating for any autoimmune conditions, genetic causes, other etiologies of cirrhosis. Then send initial labs to look for any complications, including things like thrombocytopenia, abnormalities in the inr, the creatinine. And then typically the next steps would be doing something like a fib4 to calculate the risk of having advanced fibrosis. If that is not low or reassuring, or if you have any conflicting data, meaning maybe the imaging and the labs don't match up, then you proceed with talking about doing some form of elastography or liver biopsy, and then for varicel screening, really screening everyone with cirrhosis. Although there is, you know, some evidence for starting a beta blocker if you're not able to do that. And typically now carvedilol is the beta blocker of choice. And the goal there is 6.25 twice a day. And then I think one thing we touched on was HCC screening, but I do think that's something that falls on primary care doctors, not infrequently, because people oftentimes see the hepatologist once a year. So maybe that's something we should delve into a little bit more. What is the recommended imaging for HCC screening and should we be getting an AFP every time?

B (47:26)

Yeah, that's a great question. I would say that right now the gold standard is still an ultrasound every six months with probably plus or minus the AFP based on the ASLB guidance. I will tell you that there is data that doing an AFP with an ultrasound increases sensitivity. And that is my practice for sure. The thing we have to be cognizant of with ultrasound is its real world sensitivity is pretty abysmal. And in certain patients, in particular those with fatty liver disease, those with child C sclerosis, Those with high BMIs, the sensitivity is even worse. And you know, there has always been a push, there's always a movement to go to cross sectional imaging or find some kind of serological screening for hcc. But I would say that that stuff is either not really viable economically or not ready for prime time yet when it comes to, like the serologic screening. So my practice right now is to do ultrasounds every six months. But I pay attention to my ultrasound reports. And if the ultrasound is suboptimal or they're saying they're not seeing well, or there's a real dense echitecture to the liver at a minimum. I will alternate with some cross sectional imaging, preferably mri. But if that's not possible, then CT scan, the mri, just primarily just the lack of cumulative ionizing radiation. I, I like to just try to use MRIs so I don't run into that problem. So, you know, after, you know, six years of getting every six month scans, that can end up being a lot of radiation for a patient. So that's sort of my practice, you know, six months to six months, that's, that's definitely the gold standard. Your basic basic surveillance should be an ultrasound plus an AFP, in my opinion. And then, you know, cross Sectional imaging, if the imaging is suboptimal or they see anything on the ultrasound.

A (49:32)

So, Scott, I just want to make sure I'm clear on this. Where you don't only have to order the imaging, we're also supposed to read the imaging reports when they come back.

B (49:38)

Yeah, unfortunately, this feels. I know it's.

A (49:41)

This feels like a. I'm just.

B (49:42)

I'm just saying it's not fair.

A (49:44)

All right, well, having said that, why don't. Why don't we make Ms. Pauline even more complicated? Lena, let's. Let's take. Let's talk to the next part of the case.

C (49:52)

All right? Yeah. So now Ms. Paulina, she's hospitalized with SVP and now presents to follow up again in clinic. So what is decompensated cirrhosis? And why does it matter?

B (50:03)

Yeah, it does matter. Quite a big deal, right? So decompensated, and there's some confusion around decompensation. I would say that even among some of my learners here, like, there's some question about what counts for decompensation, what doesn't. But basically, decompensation is development of clinically overt complications of portal hypertension. Okay. And I mentioned. I said. Notice I mentioned portal hypertension and not cirrhosis. You know, so these. These are the complications of ascites. Overt ascites, variceal bleeding, and overt encephalopathy. That. That's what counts as. As decompensation. So when your patient goes from being fine, then all of a sudden they show up with fluid in their belly, that's decompensation. Or if they show up with a variceal bleed, what's not a decompensation is if they get a little more jaundiced than they usually are, if their MELD score goes up a little bit, or if they develop liver cancer. A lot of people think getting a liver cancer equals decompensation, but it doesn't, and not by the strictest definitions. And why does it matter? Because we know that compensated patients with compensated cirrhosis, their survival is pretty good. I mean, I think their median survival is like, over 12 years when you look at the literature. Whereas decompensated cirrhosis, your median survival is less than a year and a half, typically. So once a patient decompensates, that's kind of a huge deal. And that's usually if they haven't seen the hepatologist by that point, they need to. You know, if you have a transplant program at your disposal, that's a great Time to head them in that direction. Because once you get decompensation, your survival really goes down fairly dramatically.

A (51:43)

Can I ask a fundamental question? Because my role here is to ask the dumb questions, but once you decompensate, is it decompensated cirrhosis? Always and forever. Because often these things can be transient or resolved. So once you've crossed that Rubicon, are you always considered decompensated or can you undecompensate or become compensated again? Undecompensated is probably not the best way to say that. Now that I think it's true.

B (52:05)

My medical student at Cashalak Medical School asked me that very question today. You know, that is a good question. And in my mind, once you're decompensated, you're decompensated. I don't know that there's any great guidance on when you can become uncom decompensated again. But you're right. I have patients that are like, five years ago they had ascites and we treated their hepatitis C, and now they're perfectly fine. They don't have ascites anymore. Not even on diuretics anymore. At some point I start calling those people clinically recompensated. Or I'll say they were decompensated, but they've recompensated, But I don't know exactly when. The cutoff to do that is. You see that a lot with alcohol. Right. I'm sure you've seen these folks that come in, yellow belly's full of fluid, really, really sick, and then nine months later, they're staying away from alcohol. And you would never know that they had a medical problem. They don't have ascites. They're not jaundice. Their labs are normal. Like, everything's wonderful. If you do a scan on them, they still have cirrhosis, but they have a very functional liver. We see that dramatic improvement in three to six after alcohol cessation. But, yeah, I'd say I've kind of described them as clinically recompensated, but they still have that decompensated moniker. Once it happens.

A (53:20)

That's extraordinarily helpful. And that was the exact circumstance I was thinking of. I feel like I've seen a few patients that just recover remarkably well but still have cirrhotic morphology. But they don't even need the medications presently and just sort of how to think about them. But that's very helpful. Thank you.

C (53:32)

Yeah. And I think we talked how you would treat esophageal pharisees and Now, I think it'd be helpful to discuss ascites. So say, you know, in Ms. Paulina's case, she developed ascites, had SVP. But what would be your kind of management guidance for initial treatment of ascites?

B (53:55)

You know, ascites is kind of a big deal for your cirrhotic patients. And, you know, it's not just fluid in the belly and uncomfortable discomfort. It's a big prognostic badness with regards to their overall survival. It really portends the onset of the. That nutritional disaster that we run into with, with the Sarcopenian frailty. And so management of ascites, you know, the sort of classic example, management of ascites is, you know, number one is you talk to them about sodium and sodium restriction. But we've kind of already talked to, talked about my sort of philosophy on that front. First line therapy for ascites is diuretics. Obviously, and most folks practice is to use a loop diuretic in combination with spironolactone. And we use a ratio of 20 to 50 here, 20 milligrams of furosemide, of 50 milligrams of spironolactone. But we usually start at 40 milligrams of furosemidE, 100 milligrams of spironoLactone. That's once daily. I always see that these diuretics, especially the spironolactone providers, love to dose that twice a day, like in the morning and the evening. I always tell them, just take all your medicine together once a day in the morning. These are threshold drugs, and you typically are going to get more bang for your buck with a higher dose once a day than smaller doses twice a day. But at least here at vcu, we do these things what we call steps. So step one is 40 of furosemide, 100 of spironolactone. And then step two is we double that. And then step three is we, you know, triple it. And then step four is we quadruple it. So that's kind of we just slowly step up the diuretics until we either have the ascites under control or they can't tolerate it anymore and they get, you know, either aki or hyponatremia or severe cramping or something where the diuretics just can't be used. And at that point, they've essentially become refractory ascites, which is a beast of its own color there that we have to worry about. I would just add that you do have to I mean, once they develop ascites, the other thing that you have to start thinking about is sbp. And our patient got SBP in this example. And SBP is kind of a huge deal with a huge mortality attached to it, like up to 30% mortality associated with an SPP episode. When a patient rolls into the hospital with ascites from liver disease with any complaint at all, they should get a parasynthesis, like, at least to get a diagnostic paracentesis with a cell count, with differential to rule out spp. Because SBP can literally present in any way that you can possibly imagine with encephalopathy. Variceal bleeding, abdominal pain, abnormal labs, sometimes no complaint at all. But if you don't recognize it quickly, then the patients have a tendency, a nasty tendency of developing hepatorenal syndrome and dying on you. So, you know, that's the one thing I preach is with sbp, is tap early and tap often. Just find it quick and get it treated and not don't, don't wait till the third day of hospitalization when the procedure team can finally roll around to do the paracentesis to diagnose sbp.

C (57:25)

So another complication I think we should discuss is hepatic encephalopathy. What is, you know, you see this managed in different ways, Lactulose, Miralax, some combination of the above. What is your general recommendation?

B (57:41)

Well, I think the first thing to realize with encephalopathy, encephalopathy, is it's not just ammonia. And you know, a lot of people, oh, it's just ammonia elevation. It's much more complicated than that. Encephalopathy is a complex interplay between shunting of blood around the liver, liver dysfunction, and sarcopenia, the muscle loss, the muscle wasting of liver disease. I mean, your muscle metabolizes a significant chunk of your ammonia in general. And as we lose our muscle mass more and more, we become more and more prone to encephalopathy. So I think nutritionally, you know, it's kind of weird because back in the day, we used to treat encephalopathy with a protein restriction. And I'm hoping that there's very little of that practice left out there in the world. But we should never be protein restricting a patient with cirrhosis for this simple purpose. So I do think that nutritional therapy and trying to at least stem the tide of sarcopenia is an important part of encephalopathy management. My feelings on ammonia levels, I've talked about them on prior episodes. Not a big Fan. Not a big fan of using ammonia levels, though I've softened slightly like I do. I feel like ammonia can be useful. It's been shown that if ammonia level is low in a cirrhotic, then hepatic encephalopathy is less likely cause of their altered mental status. There's some more recent data that an elevated ammonia level can portend poor outcomes in patients with cirrhosis, but I don't think that that can really be used clinically at this point. And so I would say for most patients with cirrhosis, monitoring and certainly titrating lactulosis doses based off of ammonia levels is not a great practice. Encephalopathy is a clinical diagnosis. Make the diagnosis by looking at your patient and talking to them, and then don't make it based off of a lab. With regards to lacto, the old lactulose versus Miralax debate, I would say that opinions are all over the place on this one. My opinion on the matter is that pooping certainly matters. And that's why I think a lavage with. With. With PEG probably helps. But there is also magic in lactulose, and that's what I tell patients all the time. I say, I know it's miserable, I know it's gross, but there's magic in lactulose and lactulose. Lactulose, in my opinion, is superior to. You just can't put people on Miralax and expect to have the same outcome when you have somebody on lactulose. I don't think we fully understand how it works or why it works. It may be gut biome modulation, it may be prebiotic actions. You know, it may be acidification of the gut lumen. I don't think we really know. But what we do know is when you take lactulose, you poop out more ammonia. So. And we know that it clears up encephalopathy. So even my patients with sort of baseline loose stools, I try to get them to take a little bit. I'm like, all right, well, just take a tablespoon a day. If that's all you can get away with, just, just try to get some lactose. You want to try to get about three or four bowel movements a day. I don't want them having 10 bowel movements a day. And if they are, even if they're having encephalopathy issues, I will tone it down. I'll drop the lactalose dose. Rifaximin, great drug. I love it. For me, it's still a second line therapy. If lactulose alone is not getting the job done or they're not tolerating, it still remains, unfortunately very expensive and out of the reach of some patients. But I use it liberally and just for completion's sake.

A (61:07)

I should mention when we're talking about Miralax, we're referring to polyethylene glycol specifically.

B (61:10)

Right, yeah, sorry, polyethylene glycol or any of that.

A (61:13)

No, until they sponsor us, I want to make sure we don't judge references.

B (61:17)

Polyethylene glycol for sure.

C (61:20)

Great.

A (61:20)

All right, what other terrible things do we want to do to our patient Alena?

C (61:23)

Yes. So now Ms. Pat, she's requiring frequent paracentesis every couple of weeks for CITES management. So when do you think about a TIPS procedure? What kind of is it in short term? And how is clinically significant portal hypertension defined in that setting?

B (61:43)

So clinically significant portal hypertension, it's pretty self explanatory definition, but how you actually define it is a little more specific. It's a little complicated and it's usually based off of, of transjugular hepatic venous pressure gradient measurements, which I don't know how many people actually do those. Like in Europe, they just slap people on a table and do a transjugular probe and just measures their hvpg. I don't do it very often. I typically will get HVPG measurements as part of a transjugular liver biopsy type protocol. But we know that a hepatic venous pressure gradient, and basically what that is, is they put the balloon in the hepatic vein, they blow up the balloon, measure the distal wedge, if you will, and then lower the balloon and then measure the pressure in the hepatic vein and subtract the two. And what it is, is it basically gives you an estimation of the portal vein pressure and a hepatic venous pressure gradient of 10 millimeters of mercury or more is clinically significant portal hypertension. So a normal hepatic venous pressure gradient is less than 5. So anything above 5 is portal hypertension. Anything above 10 is clinically significant portal hypertension. Why is it clinically significant? Because that's where people start to develop ascites. That's where people start to develop varices. Right. So that's why it's clinically significant portal hypertension, if that's noted. Now, clinically, you don't need a hepatic venous pressure gradient. If the patient has varices, or if they have ascites, especially a high sag lower protein ascites, then they have clinically significant portal hypertension. You all need to poke a needle in their neck to make that diagnosis. Okay. And there are sort of more, more recent sort of movement towards defining this using non invasive measures like we're using the vibration control, transient elastography. If you combine the liver stiffness, as I mentioned earlier, with platelet counts, you can make this diagnosis. So like if their stiffness is somewhere in the 15 to 20 range and they have platelet count less than 110, that's considered clinically significant portal hypertension. If their stiffness is 20 to 25 and their platelets are less than 150, that's clinically significant portal hypertension. If they have a stiffness over 25 with any platelet count, that's considered clinically significant portal hypertension. So there's several different ways to define it, but basically it's the point of portal hypertension where it starts to become deleterious to the patient. They start to develop complications from it. You asked about a TIPS procedure. TIPS transjugular intrahepatic portal systemic shunt is just that. I always describe to my patients that portal hypertension is essentially a plumbing problem. The liver being an organ that's collecting about 25% of your cardiac output, has a lot of blood flow through it. And it is basically a scarred up fibrotic mess that the blood has a hard time getting through. And as a result the pressure goes up in that portal vein. What a TIPS allows us to do is bypass that. I always describe cirrhosis as sort of like a sewer pipe full of tree roots. And what we can do with the TIPS is we can just build a pipe around that. And so interventional radiology will get into the hepatic vein. They will randomly poke needles throughout the liver, injecting dye until they get a portal venogram, at which point they will then put a wire into the portal vein, dilate that tract and put a covered metal stent in there. And basically what that allows to happen is that portal venous blood flow can now flow preferentially through that low pressure stent and into the vena cava and the right atrium of the heart. This immediately decreases portal pressures dramatically and as a result it has beneficial effects on ascites as well as varices. Once you put a TIPS in, your risk of variceal bleeding is basically non existent unless you have gastric varices and ascites. Will typically get better, though it doesn't immediately go away. Usually my practice when I put a TIPS in someone is I have their diuretics initially. So if they were on, say, 80 of furosemide and 200 of spironolactone, I might drop them to 40 and 100. And what you'll see over the next probably four to six weeks is that their diuretic regimen or their need for paracentesis will get smaller and smaller and smaller as the. As the TIPS sort of matures. So, you know, if it does all of this stuff for us, why don't we just put them in everybody? Well, that's a great question, because they always. They sound so good on paper. Like, why don't we just throw a tips in everybody? Well, the problem is there's a couple of downsides, right? So there's a couple of downsides to a tips. A big one is encephalopathy. So I mentioned earlier that encephalopathy, a big part of encephalopathy, is shunting. Well, you put a TIPS in, you're putting a pretty big shunt in, right? And as a result, about 30 to 40% of people you put a TIPS in will have encephalopathy afterwards. And you just have to prepare them for that because encephalopathy is a devastating diagnosis for people. People hate encephalopathy. They kind of lose themselves, and it's very scary. So you just kind of have to warn them about that risk. Now, typically is manageable, but it is a big complication. The other thing is that you increase the preload on the heart, at least acutely, pretty dramatically when you put a TIPS in. And if a patient has pulmonary hypertension or stiff heart or something like that, you can run into heart failure issues. And that's another reason why we don't do it. Typically in patients, say, on dialysis or have really poor renal function, you have to be careful because they can't handle the fluid, and they'll end up with pulmonary edema afterwards. And the other thing that happens is you're acutely shunting away two thirds of the liver's blood pressure flow, right? So, I mean, and that can kind of shock the liver out. So a lot of people don't know this, but the MELD score, our favorite little calculation that we do, was initially created to determine who would live or die after a TIPS procedure. That's like, that's how then why the meld was created. And now we're talking about old school meld. We're not talking about meld 3o or meld sodium, any of those guys. We're talking about old school meld. And usually an old school meld of around 18 is sort of your inflection point point. So above, above 18, your risk of dying of liver failure after a TIPS goes up significantly. So you have to be a little careful with tips. I always say when you mess with portal hypertension, you don't know what you're going to get on the other end. You have to be a little bit cautious and do these things thoughtfully. So that's why we don't just slap TIPS in everybody.

A (68:21)

So you. So let's say for Ms. Psaqui, she undergoes the TIPS procedure. She does fantastically well. We don't precipitate encephalopathy or send her screaming into volume overload or anything like that. So she follows up and her MELD score in the clinic is 19. So you'd actually. Your meld 3.0 score is 19. You mentioned the meld 3.0. I feel like I'm two meld scores behind that. So I don't know that I'm that familiar with this as a concept. So could you catch me up? What have I missed as I've been ignoring the liver literature, I guess, for the past eight years? What is MELD 3.0, how do we use it and how do we talk to patients about it?

B (68:52)

Yeah. So the MELD score is an interesting thing. As I mentioned, it was initially developed to see who would live or die off of a TIPS procedure. But we rapidly realized that it was a pretty good measure of 90 day mortality with liver disease in general. And it ultimately became the stratification tool for liver transplant. So when you're on a liver transplant list, where you are on the liver transplant list is based off of your MELDS score. And the MELD score is initially three calculations. Right. So the inr, the creatinine and the bilirubin. Right. So those are the three variables in the original MELD score. Over time we realized, hey, that the sodium level is independently associated with bad outcomes. So we added the sodium and it became the MELD sodium score. And the MELD sodium score was the rule of the game for a little while, for a couple of years. But what we started to notice is that certain groups are being disadvantaged by the MELD score. There are certain populations that are being disadvantaged because the second highest weighted variable on the MELD score is the creatinine. And if you know anything about Physiology, you know, that men have higher creatinines than women do. Okay. And this was leading to a palpable and very real disparity between men and women on the transplant list. And men would have an average MELD score, sometimes one to two points higher than a female of, you know, very similar liver sort of severity. And so a movement was undertaken to come up with a more equitable scoring system. And the end result of that was the Meld 3.0. And Meld 3.0 was rolled out in July of last year, so July of 2023, and is now the law of the land when it comes to transplant. So how is meld 3.0 different than meld sodium? Well, they added back albumin. So now albumin is part of the calculation. Biologic sex is actually part of the calculation now. So you literally go, and you click male or female on that. And then the creatinine became capped at three rather than four. So back in the old MELD calculator, when you, you know, at the bottom, you'd always have to say, is the patient on dialysis? If you put the patient's on dialysis, then they're. Their creatinine would become 4 for the calculation. Now if you do that, their creatinine becomes 3 for the calculation. So it changed that. And they also changed some of the coefficients for creatinine and bilirubin. They sort of adjusted things around and the end result of this was just rolled out. But what they showed is that the allocation has sort of equilibrated somewhat between those two groups. But of course, it's raised a whole other can of worms, as these things always do. And I doubt, I'm sure that there will be a meld 4.05.060 before all is said and done. But the meld 3.0 is what we're dealing with currently.

C (71:52)

Do you have a general way you think about the results of that score that you might describe to a patient? I guess, yeah.

B (72:01)

I usually talk to patients about MELD score mostly, again, in the context of transplant. Most of my folks that I'm spending a lot of time talking about MELD scores are people that are heading towards transplant or on the transplant list. And I do spend some time educating them about that and just kind of telling them what it is and what a normal MELD score is, because they're going to hear it. They're going to hear it, you know, and when they're in the hospital and say, oh, I heard my meld score. Is 28. And someone told me that means that I'm number one on the transplant list or something. So they hear things like this, and I basically just educate them that, look, it's. It's. And they. They freak out if it changes, right? They're like, oh, my God, my melt score is 22. It was 20 last time we checked it. And. And so I'd say, look, if this is just a calculation that we do based off of your labs, and it's going to bounce around some, you know, it's going to go up, it's going to go down, it's going to kind of wiggle around based on what your labs are looking like that day, I. I kind of give them an idea. You know, seven is normal. If you don't have liver disease, your melt score is 7. You know, 15 is where we put people on the transplant list, and we know that 15 is the kind of point where you're more likely to die of liver disease than you are of a liver transplant. Okay? So that's an important number for us, you know, 15. And then we, you know, we transplant people on average at a MELD score of X, Y or Z, depending on what it is right now, you know, and just to kind of give them a sense for, you know, okay, well, you know, my meld score is 18. Where does that put me? And I'll say, well, okay, that, you know, that's kind of. That's sick enough to be on the transplant list, but you're not going to be at the top of the transplant list right now. But, you know, so I just sort of counsel them about that.

C (73:39)

So when should we think about a liver transplant evaluation for a patient? Or when should we send them to hepatology to be evaluated?

B (73:49)

Yeah, this is a very important point, and I think we've mentioned a couple of times in sort of evaluation of our patient today at. There are certain inflection points where you could easily send someone to a hepatologist. But sometimes, you know, I live in the spoiled world where I work in a transplant program and we have this huge quantity of transplant hepatologists sort of floating around that can see patients. But maybe if you live in, you know, a more rural part of the country or something, you might not have that availability, and you might be managing these people a little deeper into their disease. But I would say that anytime that a patient has decompensated, we talked about that, that decompensating event, even if it's the first decompensating event, their Survival goes down dramatically at that point. And I think realistically that is the best time to get them to a transplant hepatologist to start evaluating someone for a transplant. I always describe to my patients that having decompensated cirrhosis is a little bit like walking on a tightrope. We talked about the patient that recompensated. I said, you're walking on a tightrope and any little breeze could blow you off of that tightrope physiologically and lead you into multi organ failure. And if you're not on a transplant list, if you haven't been evaluated for transplant, there's nothing to catch you there but jagged rocks, right? And being evaluated for a transplant is not necessarily a destination. I'm not necessarily evaluating you for transplant to try to get you a liver transplant. My goal in putting you on the transplant list and evaluating for liver transplant is to get a safety net under you, okay? As you're walking on that tightrope, if that breeze blows you off, you got a transplant there to catch you. You know, if, if. And that, that's kind of what I think about it. So I think any decompensation, really, unless there's like extreme extenuating circumstances, I would, I would refer the patient and you know, I would even advocate for not, not spending a lot of time making social judgments about a patient and whether they're worthy of a transplant, you know, because this is something I see a lot of. They don't get sent to us because they drink alcohol still, you know, or they don't get sent to us because, you know, they don't think they have good enough social support. I would always let the transplant center make those judgments because we're working very, very hard on management, treatment and you know, of alcohol use disorder. We're transplanting people very early in their alcohol use disorder sobriety journey. You know, I, and I hate to see patients get, you know, not sent, not sent, not sent because, you know, oh, we think they need six months of sobriety. That the six months of sobriety has died at this point as a concept. And you know, I would say that transplant centers in general want to see these people sooner rather than later. And then the other time you want to send somebody is if they're having other complications of cirrhosis that are not necessarily being reflected by the MELD score. So, so, you know, if a patient is having very severe encephalopathy or if a patient has like hepatopulmonary syndrome, portal pulmonary hypertension, certainly if they developed A tumor, a mass encephalopathy, anything like that, or, you know, something weird like, you know, some, some patients with cirrhosis just continuously bleed. You know, they just ooze like constantly from their GI tract. You need blood transfusions like every, every couple of weeks. So their meld score is 8. They need to be sent for a transplant of and a transplant evaluation. So basically, if they've decompensated or if their liver is giving them any sort of trouble, that's when we need to see them. Because, you know, their mouth score doesn't necessarily need to be high to get transplanted. You know, living donor liver transplant allows us a tremendous amount of latitude to get folks transplanted, even, even sometimes at lower melt scores. So I would say earlier is better and we want to see more, not less.

A (77:38)

That's great. I love that framing. Thank you so much for that. All right, well, Scott, this has been tremendous. I feel much more empowered to take care of livers in general and actually talk to patients who are living with cirrhosis. Before we let you go for the night, and you've been with us for a good long time now, are there any particular take home points you'd like our listeners to leave this episode with or they should not leave this episode without?

B (77:58)

Yeah, I think the key, one of the key things that I want to get out to the internal medicine world is, you know, try not to be afraid of the liver. And I know that a lot of people just simply don't understand the liver or don't even really think about it too much, and also sort of be cognizant of liver disease and its growing impact, especially with the development of the fatty liver disease sort of epidemic in this country. I just saw a patient recently in my clinic who came to me for a first visit of cirrhosis, telling me he had just been diagnosed with cirrhosis. And I looked in our emr, which is a national emr, and I can see, you know, CAT scans going back for years, and I looked at CTA abdomens dating back eight years, and every one of them was saying, cirrhosis with varices. Cirrhosis with varices. And no. 1. And the guy's got low platelets, Billy Rubin's elevated, and he's like really sick now and 70 something years old. So it's like that makes a huge difference. And, and he's been seen by 40 different doctors of the internal medicine ilk, you know, and, you know, that's the kind of thing that, that concerns me is because Liver disease flies under the radar. You don't, you don't recognize that alt of 45 is abnormal. You don't, you don't, you don't notice that the, the CAT scan is saying that the liver is nodular. So I would say just, I would just, my, I would cry out to pay attention to the liver and get folks to us sooner so that we can, you know, the goal of hepatology is to get people earlier in their cirrhosis so that we can keep them compensated. You know, that's, that's kind of our goal is to keep people compensated. Once they come to us and they're like bordering on severe decompensation and stuff, they're, their survival goes way down and our ability to help them also goes way down. So I guess that's my, my, my take home message is be on the lookout for liver disease because it's out there and it's everywhere. And with the, with the fatty liver disease epidemic, it just seems to be getting worse every year. So that's all I got for you guys. I hope this was helpful.

A (80:13)

This was fantastic. Is there anything that you'd like to plug, any, any personal plugs or any resources that you'd like to shout out before we let you go?

B (80:19)

Oh, good lord, no. I'm boring as boring can be. I have nothing to.

C (80:24)

No, you're a power lifter.

B (80:26)

Yeah.

C (80:26)

Thank you. This is great.

A (80:32)

This has been another episode of the Curbsiders bringing you a little knowledge food for your brain hole.

C (80:38)

Yummy.

A (80:41)

Still hungry for more. Join our Patreon and get all of our episodes ad free, plus twice monthly bonus episodes at patreon.com curbsiders. You can find our show notes@thecurbsiders.com and sign up for our mailing list to get our weekly show notes in your inbox. This includes our Curbsiders Digest, which recaps the latest practice, changing articles, guidelines and news, and internal medicine.

C (80:57)

We're committed to high value practice changing knowledge and to do that, we need your feedback. So please email us@askcurbsidersmail.com it also helps a lot when you subscribe, rate and review the show on YouTube, Spotify or Apple Podcasts. A reminder that this and most episodes are available for CME credit for all health professionals through VCU Health at curbsolutors.

A (81:17)

Vcuhealth.Org and I'd like to give a special thanks to our writer producer for this episode, Dr. Elena Gibson, also my outstanding co host for the episode, and to our whole Curbsiders team. Tactile production is done by the team at Podpaste. Elizabeth Proto does our social media. Jen Water runs our patreon. Chris thechewman Chew moderates our discord. Stuart Brigham composed the theme music. And with the. With all of that, until next time, I've been Dr. Paul Nelson Williams and Alaina Gibson here.

C (81:40)

Thank you and good night.