June 15, 2026
MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease)
Dr. Sam Sanders, internist at Bellevue Hospital in NYC, takes us through a case-based review of metabolic dysfunction–associated steatotic liver disease (MASLD), an increasingly common condition. We cover updated terminology, risk stratification using FIB-4 scoring and FibroScans, indications for hepatology referral, and new management strategies to prevent fibrosis progression and cirrhosis.
Our Sponsors:
* Check out FIGS and use my code FIGSRX for a great deal: https://wearfigs.com
Advertising Inquiries: https://redcircle.com/brands
WEBVTT
00:00.031 --> 00:01.132
[SPEAKER_01]: Welcome back to run the list.
00:01.352 --> 00:12.419
[SPEAKER_01]: My name's Emily Gatowski, and today I have with us Dr. Sam Sanders, internested Bellevue Hospital of New York City Health and Hospitals in Assistant Professor of Medicine at NYU Grossman School of Medicine.
00:12.639 --> 00:14.781
[SPEAKER_00]: Dr. Sanders, thank you so much for joining us.
00:15.141 --> 00:16.402
[SPEAKER_00]: Thanks so much for having me.
00:16.702 --> 00:33.033
[SPEAKER_01]: So today we'll be discussing a very interesting topic referred to as massaled or metabolic dysfunction associated stathotic liver disease, which some of our listeners might be more familiar with previously as naffled and we'll get into some of the terminology a little bit later because there have been some changes.
00:33.613 --> 00:37.716
[SPEAKER_01]: So Sam, can you tell us a little bit about why you feel passionate about this topic?
00:37.756 --> 00:41.218
[SPEAKER_01]: Why this is an important topic for learners to get an update on?
00:41.458 --> 00:42.359
[SPEAKER_00]: Yeah, absolutely.
00:42.419 --> 00:45.221
[SPEAKER_00]: So as a primary care physician, I feel like we see
00:45.896 --> 00:53.023
[SPEAKER_00]: mildly elevated LFT is all the time in clinic and often times the cause of it is mazzled.
00:53.504 --> 01:02.713
[SPEAKER_00]: I work in a clinic where a lot of our patients also have other diseases that fall into this broader category of metabolic syndrome and so there's a lot of interest.
01:03.193 --> 01:05.155
[SPEAKER_00]: in this disease area in particular.
01:05.895 --> 01:09.618
[SPEAKER_00]: And, you know, mazzles is really an epidemic on the rise.
01:09.718 --> 01:13.901
[SPEAKER_00]: You know, it's prevalence is really increasing, especially within the United States.
01:14.222 --> 01:20.486
[SPEAKER_00]: And it's something that as a general internist, we have a lot of power to treat and to counsel our patients about.
01:21.267 --> 01:28.652
[SPEAKER_00]: And so for all of these reasons, it's such an important topic for all general internists and really excited to talk about it today here.
01:29.113 --> 01:30.554
[SPEAKER_01]: All right, so let's get into our case.
01:30.892 --> 01:36.146
[SPEAKER_01]: We have Mr. F, he's a 64-year-old gentleman with history of Type 2 diabetes.
01:36.636 --> 01:42.218
[SPEAKER_01]: Obesity, hypertension, and hyperlipidemia, who presents to his PCP for his annual visit.
01:42.758 --> 01:45.579
[SPEAKER_01]: He's taking metformin, licenna pralina torvastatin.
01:45.919 --> 01:54.323
[SPEAKER_01]: He feels generally well, no real complaints, and during their visit his PCP discusses the importance of losing weight and the role that Obesity plays in his other medical conditions.
01:54.783 --> 01:58.304
[SPEAKER_01]: He gets some basic labs drawn, and they come back with an AST of 55 and ALT of 76.
02:01.205 --> 02:03.007
[SPEAKER_01]: and these were previously normal a year ago.
02:03.447 --> 02:08.071
[SPEAKER_01]: The rest of his labs, including a CBC, are normal, including a platelet, count of 260.
02:08.531 --> 02:12.554
[SPEAKER_01]: As his PCP reviews his lab results, she takes a look at his prior imaging.
02:12.594 --> 02:20.180
[SPEAKER_01]: He actually had an abdominal ultrasound done a couple of years ago for abdominal pain at the time that showed incidental hepatic stethosis.
02:20.721 --> 02:27.866
[SPEAKER_01]: So Dr. Sanders, before we get into the weeds of this case, can you tell us what exactly hepatic stethosis is and how it relates to massaled
02:30.140 --> 02:48.721
[SPEAKER_00]: Yeah, absolutely, so Stetosis refers to fat in the liver, and we really think about a healthy liver as having less than 5% of fat within hepatocytes, the cells of the liver, and Stetosis really refers to a liver with greater than 5% of hepatocytes.
02:50.342 --> 02:50.943
[SPEAKER_00]: with fat.
02:51.524 --> 03:11.905
[SPEAKER_00]: In terms of the progression of this disease, you start off with a healthy liver, and then as you accumulate fat in the liver, you develop stytosis, and that is really known as mazzled in this case if it's related to metabolic dysfunction, and then that can further progress on-word, and
03:12.425 --> 03:22.408
[SPEAKER_00]: to something called mash, which is metabolic dysfunction associated stiato hepatitis, and then that eventually can develop into cirrhosis.
03:22.808 --> 03:34.672
[SPEAKER_00]: And so that's really the progression from a healthy liver to liver with, you know, stiotosis, in this case, related to mazzled, and then eventually to mash and to cirrhosis.
03:35.432 --> 03:38.293
[SPEAKER_00]: And just breaking down the different categories of
03:38.753 --> 03:41.054
[SPEAKER_00]: the acronyms that I was just using.
03:41.595 --> 03:58.704
[SPEAKER_00]: Just to say the old nomenclature that we use for these disease areas were naffled, which is non-alcoholic fatty liver disease, now known as mazzled like I said, which is metabolic dysfunction associated stiotic liver disease, and that really just refers to
03:59.264 --> 04:02.585
[SPEAKER_00]: that in the liver related to metabolic dysfunction.
04:02.826 --> 04:13.150
[SPEAKER_00]: And then the ultramanology for Stiato Hepatitis related to this disease area was Nash, which is non-alcoholic Stiato Hepatitis, and it's now known as MASH.
04:14.791 --> 04:20.277
[SPEAKER_00]: So it rhymes, but it's different, and that's metabolic dysfunction associated stiato hepatitis.
04:20.357 --> 04:30.948
[SPEAKER_00]: And the idea there is the earlier stage of this disease area is just having fat in the liver, which is mazult, or stiatotic liver disease.
04:31.148 --> 04:34.912
[SPEAKER_00]: And then once you get inflammation on top of that,
04:35.192 --> 04:42.558
[SPEAKER_00]: you get something called stiato hepatitis, which is mash, and that's the metabolic dysfunction associated stiato hepatitis.
04:42.958 --> 04:53.386
[SPEAKER_00]: So you start with the normal liver, you get some fat, that's mazzled, then you get some inflammation, that's mash, and then eventually you develop a cerotic liver unfortunately.
04:53.426 --> 05:03.013
[SPEAKER_00]: And the reason why the terms were changed was really to focus less on defatty element of the liver and more on the metabolic risk factors.
05:03.453 --> 05:07.094
[SPEAKER_00]: that are underpinning your development of this disease area.
05:07.514 --> 05:18.816
[SPEAKER_00]: Our goal as general internists is really to identify, mazzled and mash in its early stages before you get to the progression of cirrhosis.
05:19.336 --> 05:23.217
[SPEAKER_00]: Because once you progress to cirrhosis, it's really not reversible.
05:23.437 --> 05:29.458
[SPEAKER_00]: And obviously there's so many complications with cirrhosis, like a patocelular carcinoma that we're trying to avoid here.
05:30.118 --> 05:40.813
[SPEAKER_00]: And so our goal here is really to just catch it early and to, you know, figure out who can be treated for it before they develop cirrhosis.
05:41.594 --> 05:45.320
[SPEAKER_00]: One thing I would say here is that the reason that I keep harping,
05:46.180 --> 05:53.502
[SPEAKER_00]: on mazzled and stiatotic liver is there are a lot of different causes of stiatotic liver disease.
05:54.182 --> 06:03.465
[SPEAKER_00]: Stiatotic liver disease is really an umbrella term for all liver diseases with accumulation of fat in greater than 5% of parasites, the liver cells.
06:03.725 --> 06:12.667
[SPEAKER_00]: You can also get stiatotic liver disease from alcoholic liver disease, drug induced causes, genetic causes, cryptogenic causes, and there's even
06:13.307 --> 06:19.148
[SPEAKER_00]: One entity called Metail D, which is basically mazzled in the setting of increased alcohol consumption.
06:19.388 --> 06:38.532
[SPEAKER_00]: So all this is to say, stiototic liver disease takes lots of different forms, but the one that we're talking about today on this podcast is the specific entity called mazzled, where you're getting that stiotosis, specifically in the setting of these metabolic risk factors and metabolic syndrome.
06:38.933 --> 06:39.213
[SPEAKER_01]: Got it.
06:39.233 --> 06:41.053
[SPEAKER_01]: You know, the terminology can be confusing.
06:41.670 --> 06:46.633
[SPEAKER_01]: One vocabulary word that makes its way into this sequence is also fibrosis.
06:46.713 --> 06:51.877
[SPEAKER_01]: Can you tell us a little bit about how fibrosis fits in here and what exactly it is and how we measure it?
06:52.587 --> 06:53.567
[SPEAKER_00]: Yeah, absolutely.
06:53.587 --> 06:56.448
[SPEAKER_00]: I know we just talked about stuff at a really high level.
06:56.628 --> 07:10.853
[SPEAKER_00]: That idea of developing mazzled with the stiotosis and the fat and then that developing into mash, which is that stiotosis with inflammation as the natural progression of this disease.
07:11.853 --> 07:18.119
[SPEAKER_00]: And just to say here that inflammation that you see in match is a precondition for fibrosis.
07:18.959 --> 07:27.827
[SPEAKER_00]: So eventually, once you've progressed to match, which is when you have the fat, plus the inflammation, you are at risk of developing fibrosis.
07:27.987 --> 07:32.311
[SPEAKER_00]: And fibrosis is really progressive scarring within the liver,
07:36.755 --> 07:41.701
[SPEAKER_00]: And it is really important to talk about because it's the most important predictor of poor outcomes.
07:42.642 --> 07:50.631
[SPEAKER_00]: And eventually, if you have extensive fibrosis, you get something called confluent fibrosis, which is cirrhosis.
07:51.697 --> 08:03.664
[SPEAKER_00]: And so one thing to note is that there are a lot of ways to restratify patients that have mash, which is the Seattle hepatitis.
08:04.304 --> 08:08.587
[SPEAKER_00]: The most common way is we grade them based off of their level of fibrosis.
08:09.127 --> 08:11.548
[SPEAKER_00]: it goes from F0 to F4.
08:11.928 --> 08:15.810
[SPEAKER_00]: If it's F0, then they don't have any fibrosis.
08:16.411 --> 08:18.892
[SPEAKER_00]: F1 is very low levels of fibrosis.
08:19.252 --> 08:25.835
[SPEAKER_00]: If it's F2 to F3, we think about the patient kind of being sort of in this in-between phase.
08:25.875 --> 08:31.178
[SPEAKER_00]: They do have fibrosis, but it hasn't gotten to what we call cirrhosis just yet.
08:31.923 --> 08:38.529
[SPEAKER_00]: And if they have a four or five process, that's somebody that has mash and then cirrhosis as well.
08:38.609 --> 08:45.395
[SPEAKER_00]: They have that confluent fibrosis that leads to a very fibrotic liver and a syronic liver, essentially.
08:45.680 --> 08:54.584
[SPEAKER_00]: What I will say is that we really want to catch these patients, like I said, before they get to that F4 fibrosis, which is cirrhosis.
08:55.365 --> 08:58.186
[SPEAKER_00]: And so that's something we think about a lot here.
08:58.606 --> 09:02.948
[SPEAKER_00]: I will also say that fibrosis progression is really dynamic.
09:03.128 --> 09:04.069
[SPEAKER_00]: It's variable.
09:04.609 --> 09:06.532
[SPEAKER_00]: some patients progress really fast.
09:06.692 --> 09:11.358
[SPEAKER_00]: Once they have, you know, develop mash, other patients progress more slowly.
09:11.378 --> 09:17.025
[SPEAKER_00]: And it is reversible, which is something that we'll talk about later on in this podcast.
09:17.688 --> 09:24.210
[SPEAKER_01]: I've also heard about the scoring system called Fib 4, and I know that can also help us risk stratify certain patients.
09:24.290 --> 09:25.891
[SPEAKER_01]: Can you tell us a little bit about that score?
09:26.331 --> 09:37.435
[SPEAKER_00]: Fib 4 is really what we use in a primary care setting to restratify these patients, basically determine who needs further work up.
09:37.775 --> 09:47.359
[SPEAKER_00]: It's telling us, based off of everything we just talked about with fibrosis, what's the probability that this patient in front of me has significant fibrosis?
09:47.740 --> 09:49.320
[SPEAKER_00]: And it's a validated score.
09:49.600 --> 10:01.646
[SPEAKER_00]: You can find it on any risk calculator that uses age, astalt and platelets to determine whether patients are likely to have significant fibrosis or not.
10:02.050 --> 10:11.958
[SPEAKER_00]: We don't use it for every single patient we see in our clinic, just to talk through which risk categories we think about using this score for.
10:12.278 --> 10:16.942
[SPEAKER_00]: We would use it if we think that we've caught mazzled incidentally.
10:17.443 --> 10:20.265
[SPEAKER_00]: So we think somebody has stytosis in their liver.
10:20.305 --> 10:23.568
[SPEAKER_00]: We want to see if they progress to mash with significant fibrosis.
10:24.188 --> 10:26.349
[SPEAKER_00]: then will definitely calculate a score.
10:26.369 --> 10:38.814
[SPEAKER_00]: When I say catch it incidentally, I mean that group of patients that we see stytosis when we get a liver ultrasound or some other form of imaging or patients that have elevated LFTs.
10:39.114 --> 10:43.776
[SPEAKER_00]: For those patients, we want to calculate a fib 4 because we think that they might have mass holes.
10:44.236 --> 10:46.737
[SPEAKER_00]: We want to determine if they have significant fibrosis.
10:47.407 --> 10:55.191
[SPEAKER_00]: There are also other groups that we search for Mazelden, because these are high risk groups with high pre-test probability of Mazelden.
10:55.271 --> 11:04.956
[SPEAKER_00]: And in terms of who's worth testing, everybody with type two diabetes, you wanna screen with a fifth four, and we'll talk about how to follow up on that.
11:05.317 --> 11:07.918
[SPEAKER_00]: Additionally, patients who have obesity,
11:08.558 --> 11:12.401
[SPEAKER_00]: And then one additional risk factor for metabolic syndrome.
11:12.721 --> 11:21.067
[SPEAKER_00]: And that might include elevated BMI, pre-diabetes, hyper-tension, hyper-tribosteridemia, or low-HGL.
11:21.267 --> 11:28.912
[SPEAKER_00]: For those patients with obesity and that one additional cardio metabolic risk factor, we tend to say, let's also scream them with a fit for.
11:29.393 --> 11:29.693
[SPEAKER_00]: Got it.
11:29.833 --> 11:30.153
[SPEAKER_01]: Okay.
11:30.253 --> 11:34.476
[SPEAKER_01]: So in our patient, I think you would definitely meet those criteria
11:37.754 --> 11:40.055
[SPEAKER_01]: obesity and hypertension in hyperlipidemia.
11:40.435 --> 11:48.177
[SPEAKER_01]: So, in his case, we calculate his fifth four score using his age, his AST, his ALT, and his platelets.
11:48.757 --> 11:51.338
[SPEAKER_01]: And we get a score of 1.55.
11:51.518 --> 11:52.999
[SPEAKER_01]: Can you interpret that for us?
11:53.539 --> 11:59.541
[SPEAKER_00]: Typically, when we interpret a fifth four, it's cut off on the lower end is 1.3.
11:59.641 --> 12:03.922
[SPEAKER_00]: So, anything below 1.3 means low probability of significant fibrosis.
12:04.362 --> 12:13.029
[SPEAKER_00]: It's cut off on the upper end is 2.67, so anything above 2.67 means high probability of significant fibrosis.
12:13.070 --> 12:25.940
[SPEAKER_00]: And when I say significant fibrosis, I'm really talking about F3 and F4, which are those stages of fibrosis for a patient with a mash, who have a lot of fibrosis, or ultimately cirrosis.
12:26.701 --> 12:29.606
[SPEAKER_00]: And so if you're below 1.3, we think you're in the safe zone.
12:29.646 --> 12:36.376
[SPEAKER_00]: If you're above 2.67, we think that you have a high probability of significant fibrosis of that F3 and F4.
12:37.315 --> 12:46.100
[SPEAKER_00]: The space in between 1.3 and 2.67 is really an intermediate space, and so those are patients that need further evaluation.
12:46.340 --> 12:52.383
[SPEAKER_00]: For this patient in particular, he's 64 years old, and so we can really apply this scoring.
12:52.403 --> 13:02.328
[SPEAKER_00]: And so when we see a 5th score of 1.55, we're thinking that they're in that intermediate phase and that they need more work up.
13:02.912 --> 13:07.555
[SPEAKER_01]: And any caveat to keep in mind with a patient's fib square when you get that initial number?
13:08.236 --> 13:14.781
[SPEAKER_00]: Yeah, the one brief pearl I would say is that, like we talked about, age is part of the scoring.
13:15.301 --> 13:26.409
[SPEAKER_00]: And so we tend to think that if somebody is 65 years older or older, we want to use different cut-offs here, rather than using 1.3 as our lower end, we tend to use 2.0.
13:31.142 --> 13:42.967
[SPEAKER_00]: Um, so if somebody has a fib four score of less than 2.0, then we say there's a low probability of significant fibrosis and that's really because fib four increases independent of age.
13:43.675 --> 13:59.773
[SPEAKER_00]: Similarly, if somebody is really young, though if they're less than 35 years old, there's some discussion among the hepatology community that you should think about it more closely for these patients because they're more likely to have a lower fit for.
13:59.893 --> 14:04.598
[SPEAKER_00]: So we don't use different cutoffs with that age group, but we just use more caution when we're interpreting it.
14:05.143 --> 14:05.383
[SPEAKER_01]: on it.
14:05.564 --> 14:11.269
[SPEAKER_01]: So back to our patient, his score was 1.55, which puts him in the intermediate risk category.
14:11.510 --> 14:14.272
[SPEAKER_01]: What exactly are our next steps in working him up?
14:14.733 --> 14:19.578
[SPEAKER_00]: So if they're in the intermediate risk category, we go to fibroscan next.
14:19.818 --> 14:25.364
[SPEAKER_00]: The fibroscan is called more formally, VCTE, vibration control,
14:27.566 --> 14:34.309
[SPEAKER_00]: And fibroscan is basically a fancy ultrasound at my hospital, the hepatologist and GI folks do it.
14:34.649 --> 14:37.910
[SPEAKER_00]: It's basically an ultrasound-based measurement of liver stiffness.
14:38.190 --> 14:41.731
[SPEAKER_00]: And liver stiffness is used here as a surrogate marker for fibrosis.
14:42.132 --> 14:47.994
[SPEAKER_00]: It's not perfect for patients with, you know, morbid obesity or a lot of hepatic congestion.
14:48.474 --> 14:50.995
[SPEAKER_00]: It can affect the quality of the fibroscan.
14:51.415 --> 14:55.959
[SPEAKER_00]: because those are conditions that limit the ultrasound wave penetration at the abdominal wall.
14:56.380 --> 15:02.305
[SPEAKER_00]: But it's a really good and well-validated test that can estimate essentially.
15:02.876 --> 15:11.478
[SPEAKER_00]: what the fibrosis score is and that serves as a proxy here for the stage of fibrosis that the patient is at.
15:11.618 --> 15:17.039
[SPEAKER_00]: So it will typically tell us that the patient is at 0, F1, F2, F3, F4.
15:17.319 --> 15:21.640
[SPEAKER_00]: There also is a second type of testing that I am not as familiar with.
15:21.660 --> 15:23.020
[SPEAKER_00]: We don't use it as my hospital.
15:23.060 --> 15:29.002
[SPEAKER_00]: It's called ELF testing and that's a proprietary blood test of three different components involved in matrix
15:30.182 --> 15:46.513
[SPEAKER_00]: and that can also be used for the risk stratify an intermediate fit for and they tend to use it a lot in rural settings where they don't have access to a fibroscan or sometimes you can also use it for patients with morbid obesity where the fibroscan is not as accurate.
15:46.846 --> 15:53.672
[SPEAKER_01]: Okay, just to recap, we have a patient who has mildly elevated LFTs, we think about their comorbidities.
15:53.752 --> 16:02.859
[SPEAKER_01]: We see that they have a paddock statuses on their imaging, so we take them through this primary risk assessment, and we calculate a fib 4, and in his case it was intermediate.
16:03.179 --> 16:11.486
[SPEAKER_01]: I don't think we touched on this yet, but if his fib 4 score were elevated, would we go on to the secondary risk assessment and do the fiber scan frame as well?
16:11.747 --> 16:28.188
[SPEAKER_00]: That's such a great question, and I would say it is definitely dependent on what your practices and what your access to hepatology is like, but I would say in general, we really only do the secondary risk assessment in that intermediate probability of significant fibrosis.
16:28.688 --> 16:31.331
[SPEAKER_00]: If they have a low probability, you don't have to worry about it.
16:31.371 --> 16:35.515
[SPEAKER_00]: You'll repeat that fit for every one to three years from here on out.
16:35.715 --> 16:44.744
[SPEAKER_00]: By contrast, if you have a high probability of significant fibrosis, so the fit for is telling you, you basically have F3 or F4 fibrosis.
16:45.045 --> 16:48.188
[SPEAKER_00]: You're going to straight refer them to hepatology, typically.
16:48.208 --> 16:51.992
[SPEAKER_00]: You don't even need that fibroscan to do that secondary risk assessment.
16:52.512 --> 17:09.440
[SPEAKER_00]: then you're stuck with that middle category for those patients with this intermediate or indeterminate risk of significant fibrosis, those are the patients that you're sending to you the fibroscan or you're sending them to do the ELF if you're in a role setting and that's what you use.
17:09.860 --> 17:15.423
[SPEAKER_00]: And then to break down what you see that would make you worried enough to refer to
17:17.744 --> 17:24.349
[SPEAKER_00]: Let's say going back to our patient, you have a fib four in that intermediate or indeterminate risk profile.
17:24.809 --> 17:27.511
[SPEAKER_00]: Their fib four is 1.3 to 2.67.
17:27.852 --> 17:30.173
[SPEAKER_00]: You send them, they get their fibro scan.
17:30.353 --> 17:37.218
[SPEAKER_00]: If the fibro scan shows 8 to 12 KPA, which is the way that it measures liver stiffness.
17:37.599 --> 17:43.103
[SPEAKER_00]: That is also considered intermediate oftentimes, but you want to refer those patients to
17:46.550 --> 17:47.711
[SPEAKER_00]: on that fibroscan.
17:48.252 --> 17:59.765
[SPEAKER_00]: If you're seeing greater than 12 KPA, a lot of liver stiffness, it portends significant fibrosis, and so you're also sending those patients to hepatology.
18:00.304 --> 18:09.646
[SPEAKER_00]: But by contrast, if you have one of these intermediate patients, going back to our patient, Mr. F, they've got a 5, 4 of 1.55, they do the fibroscan.
18:09.766 --> 18:12.886
[SPEAKER_00]: The fibroscan shows less than 8 KPA.
18:13.166 --> 18:18.047
[SPEAKER_00]: That really demonstrates that the patient does not have significant fibrosis.
18:18.167 --> 18:21.708
[SPEAKER_00]: They're in the F, zero to F, one range of fibrosis.
18:22.208 --> 18:27.569
[SPEAKER_00]: And so you can lump them back in with those patients, who have a fib four that's low risk.
18:27.689 --> 18:44.500
[SPEAKER_00]: because you're seeing that this patient has a low risk of significant fibrosis and for that sort of patient you don't need to refer them to see a hepatologist after you get the fibroscan you can just continue to measure the fit for and calculate that every one to three years along with your other low risk patients.
18:45.333 --> 18:50.537
[SPEAKER_01]: And is it possible to have an elevated fib for score even with normal LFTs?
18:51.038 --> 18:51.778
[SPEAKER_01]: Absolutely.
18:51.958 --> 18:55.161
[SPEAKER_00]: You can have an elevated fib for with normal LFTs.
18:55.401 --> 18:59.965
[SPEAKER_00]: For those patients, we really advise still using your clinical judgment.
19:00.185 --> 19:08.732
[SPEAKER_00]: If your patient is normal LFTs, but the fib for is elevated, which can happen, you still should get a secondary risk assessment.
19:09.432 --> 19:17.899
[SPEAKER_00]: if the fib-4 is in this indeterminate intermediate stage, and you should still refer to hepatology if the fib-4 is extremely elevated.
19:18.340 --> 19:30.770
[SPEAKER_00]: What constitutes clinical suspicion is really up to you, oftentimes those same patients that we were discussing earlier with metabolic syndrome or diabetes, they might have mazzled or mash,
19:31.250 --> 19:33.932
[SPEAKER_00]: without having elevated LFTs.
19:34.453 --> 19:42.319
[SPEAKER_00]: And so if those patients have a food for that falls into those buckets, we still recommend acting on it like normal.
19:42.800 --> 19:53.829
[SPEAKER_00]: By contrast, one question I get asked a lot actually is what else should I be doing if a patient is coming to me with elevated LFTs.
19:54.389 --> 19:56.811
[SPEAKER_00]: And I think that those are related to
19:59.994 --> 20:06.940
[SPEAKER_00]: If you really have a high clinical suspicion for mazzled as the eDology of the elevated LFT is, you don't have to do a ton.
20:07.260 --> 20:15.768
[SPEAKER_00]: I would say repeat the LFT is to make sure that they're actually elevated, but basically what we recommend is ordering a fibrous scan if it's appropriate.
20:16.008 --> 20:21.775
[SPEAKER_00]: You can also get hepatitis serology is an iron study is as just a very basic work up.
20:22.015 --> 20:31.187
[SPEAKER_00]: You also might get a liver ultrasound, although honestly if you're getting a fibroscan anyway, that can be helpful at pinpointing whether the patient has
20:31.747 --> 20:39.992
[SPEAKER_00]: Stiatosis or not, and so you can sometimes skip the liberal ultrasound if you know that the patient's going to get a fiber a scan pretty quickly.
20:40.813 --> 20:58.824
[SPEAKER_00]: And then if those elevated LFTs stay elevated for, let's say, three or six months with no clear diagnosis based off of that initial workup that you did, that's really when we recommend going to a secondary workup, which includes auto antibody studies like anti-LKM,
21:01.866 --> 21:11.139
[SPEAKER_00]: You could also get a surreal applause man to allow Wilson's disease, you could get an alpha, one anti-tripson, and so you're just doing the broader workup at that point.
21:11.600 --> 21:15.846
[SPEAKER_00]: The one exception I would say is that if a patient has ALT or...
21:16.407 --> 21:19.708
[SPEAKER_00]: AST that's greater than five times the upper limit of normal.
21:19.828 --> 21:21.128
[SPEAKER_00]: You really do want to do that.
21:21.188 --> 21:25.029
[SPEAKER_00]: Full work-up, including the autoimmune markers, right away.
21:25.290 --> 21:31.331
[SPEAKER_00]: Masks will not cause an AST ALT greater than five times the upper limit of normal.
21:31.351 --> 21:36.453
[SPEAKER_00]: Typically, and so if you see that, it's a reason to pause and really focus on a broader work-up.
21:36.693 --> 21:37.313
[SPEAKER_01]: Okay, great.
21:37.913 --> 21:48.197
[SPEAKER_01]: So, let's say that Mr. F gets the fiber scan, his score is 11 KPA, which again is in this intermediate risk category of 8 to 12.
21:48.657 --> 21:51.238
[SPEAKER_01]: This tells us that he should see hepatology.
21:51.478 --> 21:58.520
[SPEAKER_01]: We send him to hepatology, they take a look at his case, and given that he has several risk factors that could lead to fibrosis.
21:59.068 --> 22:04.517
[SPEAKER_01]: Like we spoke about before, his obesity, his hypertension, diabetes, hyperlipidemia.
22:04.657 --> 22:07.923
[SPEAKER_01]: They think that a biopsy is not necessary for him.
22:08.686 --> 22:13.851
[SPEAKER_01]: So, Mr. F asks the hepatologist what he can do to reduce his risk of progression.
22:14.131 --> 22:16.933
[SPEAKER_01]: Can you tell us a little bit about the treatment of Masold here?
22:17.494 --> 22:18.515
[SPEAKER_00]: Yeah, absolutely.
22:18.875 --> 22:26.742
[SPEAKER_00]: I would say, you know, the goal of the treatment here is really like I said, not to sound like broken record, but it's to prevent cirrhosis.
22:27.223 --> 22:34.229
[SPEAKER_00]: And also to prevent cardiovascular disease, because liver fibrosis and mazzled and mash, they're just one
22:34.849 --> 22:40.414
[SPEAKER_00]: part of this broader metabolic syndrome and this broader slate of cardiovascular metabolic disorders.
22:40.974 --> 22:49.100
[SPEAKER_00]: And so in order to achieve those goals, the cornerstone of treatment is oftentimes non-pharmacological for these patients.
22:49.721 --> 22:52.463
[SPEAKER_00]: We really, really, really want them to lose weight.
22:53.063 --> 23:01.650
[SPEAKER_00]: And in addition to thinking about non-pharmacological ways to lose weight, there's now obviously so much on the market and so many tools that we have in our arsenal.
23:02.250 --> 23:05.291
[SPEAKER_00]: to, you know, help patients lose weight in other ways, too.
23:05.811 --> 23:16.813
[SPEAKER_00]: I really hammer home weight loss with these patients because if you have even a 5% reduction, there are proven studies that show that you have less stytosis in your liver as a result.
23:16.853 --> 23:21.815
[SPEAKER_00]: So let's say you lose 5% of your body weight, you're going to lose fat in the liver, too.
23:22.115 --> 23:26.376
[SPEAKER_00]: And if you have 7 to 10% loss of body weight, then
23:28.526 --> 23:35.249
[SPEAKER_00]: complicated by fibrosis, we actually see a reversal of fibrosis and fibrosis reduction.
23:35.750 --> 23:39.011
[SPEAKER_00]: And so weight loss is absolutely the cornerstone of this.
23:39.672 --> 23:48.556
[SPEAKER_00]: Non-pharmacologically we tend to think about a Mediterranean diet, all of the lifestyle and dietary counseling that we tend to do around minimizing process meets.
23:49.076 --> 24:02.428
[SPEAKER_00]: ultra-processed foods, sugar-sweetened beverages, recommend physical activity, greater than 150 minutes a week of moderate intensity, physical activity, or 75 minutes a week of vigorous physical activity.
24:02.568 --> 24:06.611
[SPEAKER_00]: And we also counsel avoiding alcohol in particular.
24:06.631 --> 24:12.917
[SPEAKER_00]: There's actually no safe level of alcohol use for their literature in these patients, so we counsel a lot around that.
24:13.377 --> 24:27.939
[SPEAKER_00]: We use a lot of GLP1 agonists in my practice and also GLP1GIP at dual agonists, and so those are very, very exciting and more to come in that pharmacological area as well, I think.
24:28.339 --> 24:32.982
[SPEAKER_00]: We additionally tend to refer a lot of our patients for bariatric surgery.
24:33.482 --> 24:38.505
[SPEAKER_00]: If they meet criteria at the hospital that I work at, we have a really, really strong bariatric program.
24:38.906 --> 24:44.189
[SPEAKER_00]: And so that can be also very helpful for this disease too if the patient is motivated and interested in that.
24:44.789 --> 24:54.455
[SPEAKER_00]: And then I think we'll talk about this in just a second, but there's also one FDA approved drug that I don't prescribe myself, but the hepatologists do prescribe in terms of treatment as well.
24:55.101 --> 25:00.764
[SPEAKER_01]: I actually just saw a commercial for this when I was at the gym recently and I had never heard of it before.
25:00.824 --> 25:03.225
[SPEAKER_01]: So yes, please do tell us about this medication.
25:03.245 --> 25:04.966
[SPEAKER_00]: Okay, that's so funny.
25:05.227 --> 25:07.588
[SPEAKER_00]: I have yet to see a commercial on it, but I love that.
25:07.748 --> 25:11.530
[SPEAKER_00]: I'll just say, you know, I know there's so much drug advertising out there, but this medication
25:11.930 --> 25:14.291
[SPEAKER_00]: actually is supposed to be quite good.
25:14.671 --> 25:15.831
[SPEAKER_00]: It's called resmitterom.
25:16.132 --> 25:21.193
[SPEAKER_00]: It's the first FDA approved medication for treating mazzled and mash.
25:21.433 --> 25:32.397
[SPEAKER_00]: It is a THRB receptor agonist, which is a class of drugs that basically promote fatty acid oxidation and increase mitochondrial respiration, which reduces hepatic fat accumulation.
25:32.737 --> 25:35.398
[SPEAKER_00]: It demonstrated on studies that there was
25:40.940 --> 25:44.022
[SPEAKER_00]: to reverse fibrosis for mash and mazzled.
25:44.083 --> 25:51.568
[SPEAKER_00]: And so Resmeteram is very exciting for patients in particular who have F2 or F3 fibrosis.
25:51.848 --> 26:07.760
[SPEAKER_00]: Those are really the stages where we think it works, where the patient has enough fibrosis to qualify for Resmeteram and to need that fibraotic reversal, but not so much that they've entered the stage of F4 fibrosis or Cerosis.
26:08.380 --> 26:13.102
[SPEAKER_01]: That is very exciting, you know, this is an area that hasn't really had a lot of dedicated medications for it.
26:13.162 --> 26:15.663
[SPEAKER_01]: So, very exciting things to come there.
26:15.944 --> 26:23.807
[SPEAKER_01]: We are nearing the end of our episode, but before this patient's appointment is over, he has two more questions for our epitologist.
26:24.227 --> 26:26.868
[SPEAKER_01]: The first is that he's on a tour of a statin.
26:26.888 --> 26:30.310
[SPEAKER_01]: He's heard that these statin medications can be tough on the liver.
26:30.690 --> 26:34.652
[SPEAKER_01]: So he just wants to make sure that it's safe for him to continue staying on a tour of a statin.
26:35.703 --> 26:36.723
[SPEAKER_00]: Yeah, absolutely.
26:37.204 --> 26:38.524
[SPEAKER_00]: Stay on a tour of a statin.
26:38.624 --> 26:46.727
[SPEAKER_00]: Like we were talking about, Mazel just one part of this greater spectrum in this greater disease area of metabolic syndrome.
26:47.488 --> 26:53.290
[SPEAKER_00]: And so preventing those cardiovascular events is very, very important in that population.
26:53.330 --> 26:56.071
[SPEAKER_00]: And so definitely stay on the tour of a statin.
26:56.431 --> 27:11.261
[SPEAKER_00]: What I will say is, again, I am not a prescriber of resmitterum, the hepatologist that my institution prescriber, but I will just say it does have drug interactions for resubis statin and symbestatin if somebody's on resmitterum concurrently.
27:11.281 --> 27:14.663
[SPEAKER_00]: They'll cap the dose for those statins at 20 milligrams.
27:15.103 --> 27:20.307
[SPEAKER_00]: If somebody's on private statin or a tourist statin, they'll typically cap the dose at 40 milligrams.
27:20.347 --> 27:21.888
[SPEAKER_00]: And the idea there is just
27:22.386 --> 27:24.867
[SPEAKER_00]: to prevent any drug drug interactions.
27:25.688 --> 27:26.488
[SPEAKER_01]: Got it, makes sense.
27:26.888 --> 27:34.531
[SPEAKER_01]: And you were starting to get at this before with regard to alcohol, but he does like to go out with his friends a couple times a week and get a few beers.
27:34.832 --> 27:36.132
[SPEAKER_01]: What would you tell him about that?
27:36.432 --> 27:41.795
[SPEAKER_00]: Yeah, what I would say is, unfortunately, there's really no safe amount of alcohol in tea.
27:42.215 --> 27:46.137
[SPEAKER_00]: When it comes to Masold and Mash, there was actually a 2010 study.
27:47.352 --> 27:58.396
[SPEAKER_00]: from Scotland that showed that alcohol intake is actually super additive to the effects of increased BMI and mazled on a patient.
27:58.457 --> 28:03.979
[SPEAKER_00]: And so we think that alcohol can really accelerate the risk and progression of mazled and mashing.
28:04.039 --> 28:07.420
[SPEAKER_00]: So definitely want to counsel against that if possible.
28:07.740 --> 28:08.100
[SPEAKER_01]: Great.
28:08.361 --> 28:12.502
[SPEAKER_01]: Our patient is counseled on all of these things, including weight loss efforts.
28:12.522 --> 28:14.143
[SPEAKER_01]: He actually decides to start a GLP1.
28:15.092 --> 28:19.678
[SPEAKER_01]: and they plan to follow up again with repeat labs and imaging in around a year or so.
28:20.439 --> 28:29.029
[SPEAKER_01]: Dr. Sanders, thank you so much for helping us take such good care of our patients in the primary care setting and learning when to refer them to hepatology.
28:29.629 --> 28:30.250
[SPEAKER_01]: Such a pleasure.
28:30.270 --> 28:31.832
[SPEAKER_01]: I think so much for having me on today.
00:00.031 --> 00:01.132
[SPEAKER_01]: Welcome back to run the list.
00:01.352 --> 00:12.419
[SPEAKER_01]: My name's Emily Gatowski, and today I have with us Dr. Sam Sanders, internested Bellevue Hospital of New York City Health and Hospitals in Assistant Professor of Medicine at NYU Grossman School of Medicine.
00:12.639 --> 00:14.781
[SPEAKER_00]: Dr. Sanders, thank you so much for joining us.
00:15.141 --> 00:16.402
[SPEAKER_00]: Thanks so much for having me.
00:16.702 --> 00:33.033
[SPEAKER_01]: So today we'll be discussing a very interesting topic referred to as massaled or metabolic dysfunction associated stathotic liver disease, which some of our listeners might be more familiar with previously as naffled and we'll get into some of the terminology a little bit later because there have been some changes.
00:33.613 --> 00:37.716
[SPEAKER_01]: So Sam, can you tell us a little bit about why you feel passionate about this topic?
00:37.756 --> 00:41.218
[SPEAKER_01]: Why this is an important topic for learners to get an update on?
00:41.458 --> 00:42.359
[SPEAKER_00]: Yeah, absolutely.
00:42.419 --> 00:45.221
[SPEAKER_00]: So as a primary care physician, I feel like we see
00:45.896 --> 00:53.023
[SPEAKER_00]: mildly elevated LFT is all the time in clinic and often times the cause of it is mazzled.
00:53.504 --> 01:02.713
[SPEAKER_00]: I work in a clinic where a lot of our patients also have other diseases that fall into this broader category of metabolic syndrome and so there's a lot of interest.
01:03.193 --> 01:05.155
[SPEAKER_00]: in this disease area in particular.
01:05.895 --> 01:09.618
[SPEAKER_00]: And, you know, mazzles is really an epidemic on the rise.
01:09.718 --> 01:13.901
[SPEAKER_00]: You know, it's prevalence is really increasing, especially within the United States.
01:14.222 --> 01:20.486
[SPEAKER_00]: And it's something that as a general internist, we have a lot of power to treat and to counsel our patients about.
01:21.267 --> 01:28.652
[SPEAKER_00]: And so for all of these reasons, it's such an important topic for all general internists and really excited to talk about it today here.
01:29.113 --> 01:30.554
[SPEAKER_01]: All right, so let's get into our case.
01:30.892 --> 01:36.146
[SPEAKER_01]: We have Mr. F, he's a 64-year-old gentleman with history of Type 2 diabetes.
01:36.636 --> 01:42.218
[SPEAKER_01]: Obesity, hypertension, and hyperlipidemia, who presents to his PCP for his annual visit.
01:42.758 --> 01:45.579
[SPEAKER_01]: He's taking metformin, licenna pralina torvastatin.
01:45.919 --> 01:54.323
[SPEAKER_01]: He feels generally well, no real complaints, and during their visit his PCP discusses the importance of losing weight and the role that Obesity plays in his other medical conditions.
01:54.783 --> 01:58.304
[SPEAKER_01]: He gets some basic labs drawn, and they come back with an AST of 55 and ALT of 76.
02:01.205 --> 02:03.007
[SPEAKER_01]: and these were previously normal a year ago.
02:03.447 --> 02:08.071
[SPEAKER_01]: The rest of his labs, including a CBC, are normal, including a platelet, count of 260.
02:08.531 --> 02:12.554
[SPEAKER_01]: As his PCP reviews his lab results, she takes a look at his prior imaging.
02:12.594 --> 02:20.180
[SPEAKER_01]: He actually had an abdominal ultrasound done a couple of years ago for abdominal pain at the time that showed incidental hepatic stethosis.
02:20.721 --> 02:27.866
[SPEAKER_01]: So Dr. Sanders, before we get into the weeds of this case, can you tell us what exactly hepatic stethosis is and how it relates to massaled
02:30.140 --> 02:48.721
[SPEAKER_00]: Yeah, absolutely, so Stetosis refers to fat in the liver, and we really think about a healthy liver as having less than 5% of fat within hepatocytes, the cells of the liver, and Stetosis really refers to a liver with greater than 5% of hepatocytes.
02:50.342 --> 02:50.943
[SPEAKER_00]: with fat.
02:51.524 --> 03:11.905
[SPEAKER_00]: In terms of the progression of this disease, you start off with a healthy liver, and then as you accumulate fat in the liver, you develop stytosis, and that is really known as mazzled in this case if it's related to metabolic dysfunction, and then that can further progress on-word, and
03:12.425 --> 03:22.408
[SPEAKER_00]: to something called mash, which is metabolic dysfunction associated stiato hepatitis, and then that eventually can develop into cirrhosis.
03:22.808 --> 03:34.672
[SPEAKER_00]: And so that's really the progression from a healthy liver to liver with, you know, stiotosis, in this case, related to mazzled, and then eventually to mash and to cirrhosis.
03:35.432 --> 03:38.293
[SPEAKER_00]: And just breaking down the different categories of
03:38.753 --> 03:41.054
[SPEAKER_00]: the acronyms that I was just using.
03:41.595 --> 03:58.704
[SPEAKER_00]: Just to say the old nomenclature that we use for these disease areas were naffled, which is non-alcoholic fatty liver disease, now known as mazzled like I said, which is metabolic dysfunction associated stiotic liver disease, and that really just refers to
03:59.264 --> 04:02.585
[SPEAKER_00]: that in the liver related to metabolic dysfunction.
04:02.826 --> 04:13.150
[SPEAKER_00]: And then the ultramanology for Stiato Hepatitis related to this disease area was Nash, which is non-alcoholic Stiato Hepatitis, and it's now known as MASH.
04:14.791 --> 04:20.277
[SPEAKER_00]: So it rhymes, but it's different, and that's metabolic dysfunction associated stiato hepatitis.
04:20.357 --> 04:30.948
[SPEAKER_00]: And the idea there is the earlier stage of this disease area is just having fat in the liver, which is mazult, or stiatotic liver disease.
04:31.148 --> 04:34.912
[SPEAKER_00]: And then once you get inflammation on top of that,
04:35.192 --> 04:42.558
[SPEAKER_00]: you get something called stiato hepatitis, which is mash, and that's the metabolic dysfunction associated stiato hepatitis.
04:42.958 --> 04:53.386
[SPEAKER_00]: So you start with the normal liver, you get some fat, that's mazzled, then you get some inflammation, that's mash, and then eventually you develop a cerotic liver unfortunately.
04:53.426 --> 05:03.013
[SPEAKER_00]: And the reason why the terms were changed was really to focus less on defatty element of the liver and more on the metabolic risk factors.
05:03.453 --> 05:07.094
[SPEAKER_00]: that are underpinning your development of this disease area.
05:07.514 --> 05:18.816
[SPEAKER_00]: Our goal as general internists is really to identify, mazzled and mash in its early stages before you get to the progression of cirrhosis.
05:19.336 --> 05:23.217
[SPEAKER_00]: Because once you progress to cirrhosis, it's really not reversible.
05:23.437 --> 05:29.458
[SPEAKER_00]: And obviously there's so many complications with cirrhosis, like a patocelular carcinoma that we're trying to avoid here.
05:30.118 --> 05:40.813
[SPEAKER_00]: And so our goal here is really to just catch it early and to, you know, figure out who can be treated for it before they develop cirrhosis.
05:41.594 --> 05:45.320
[SPEAKER_00]: One thing I would say here is that the reason that I keep harping,
05:46.180 --> 05:53.502
[SPEAKER_00]: on mazzled and stiatotic liver is there are a lot of different causes of stiatotic liver disease.
05:54.182 --> 06:03.465
[SPEAKER_00]: Stiatotic liver disease is really an umbrella term for all liver diseases with accumulation of fat in greater than 5% of parasites, the liver cells.
06:03.725 --> 06:12.667
[SPEAKER_00]: You can also get stiatotic liver disease from alcoholic liver disease, drug induced causes, genetic causes, cryptogenic causes, and there's even
06:13.307 --> 06:19.148
[SPEAKER_00]: One entity called Metail D, which is basically mazzled in the setting of increased alcohol consumption.
06:19.388 --> 06:38.532
[SPEAKER_00]: So all this is to say, stiototic liver disease takes lots of different forms, but the one that we're talking about today on this podcast is the specific entity called mazzled, where you're getting that stiotosis, specifically in the setting of these metabolic risk factors and metabolic syndrome.
06:38.933 --> 06:39.213
[SPEAKER_01]: Got it.
06:39.233 --> 06:41.053
[SPEAKER_01]: You know, the terminology can be confusing.
06:41.670 --> 06:46.633
[SPEAKER_01]: One vocabulary word that makes its way into this sequence is also fibrosis.
06:46.713 --> 06:51.877
[SPEAKER_01]: Can you tell us a little bit about how fibrosis fits in here and what exactly it is and how we measure it?
06:52.587 --> 06:53.567
[SPEAKER_00]: Yeah, absolutely.
06:53.587 --> 06:56.448
[SPEAKER_00]: I know we just talked about stuff at a really high level.
06:56.628 --> 07:10.853
[SPEAKER_00]: That idea of developing mazzled with the stiotosis and the fat and then that developing into mash, which is that stiotosis with inflammation as the natural progression of this disease.
07:11.853 --> 07:18.119
[SPEAKER_00]: And just to say here that inflammation that you see in match is a precondition for fibrosis.
07:18.959 --> 07:27.827
[SPEAKER_00]: So eventually, once you've progressed to match, which is when you have the fat, plus the inflammation, you are at risk of developing fibrosis.
07:27.987 --> 07:32.311
[SPEAKER_00]: And fibrosis is really progressive scarring within the liver,
07:36.755 --> 07:41.701
[SPEAKER_00]: And it is really important to talk about because it's the most important predictor of poor outcomes.
07:42.642 --> 07:50.631
[SPEAKER_00]: And eventually, if you have extensive fibrosis, you get something called confluent fibrosis, which is cirrhosis.
07:51.697 --> 08:03.664
[SPEAKER_00]: And so one thing to note is that there are a lot of ways to restratify patients that have mash, which is the Seattle hepatitis.
08:04.304 --> 08:08.587
[SPEAKER_00]: The most common way is we grade them based off of their level of fibrosis.
08:09.127 --> 08:11.548
[SPEAKER_00]: it goes from F0 to F4.
08:11.928 --> 08:15.810
[SPEAKER_00]: If it's F0, then they don't have any fibrosis.
08:16.411 --> 08:18.892
[SPEAKER_00]: F1 is very low levels of fibrosis.
08:19.252 --> 08:25.835
[SPEAKER_00]: If it's F2 to F3, we think about the patient kind of being sort of in this in-between phase.
08:25.875 --> 08:31.178
[SPEAKER_00]: They do have fibrosis, but it hasn't gotten to what we call cirrhosis just yet.
08:31.923 --> 08:38.529
[SPEAKER_00]: And if they have a four or five process, that's somebody that has mash and then cirrhosis as well.
08:38.609 --> 08:45.395
[SPEAKER_00]: They have that confluent fibrosis that leads to a very fibrotic liver and a syronic liver, essentially.
08:45.680 --> 08:54.584
[SPEAKER_00]: What I will say is that we really want to catch these patients, like I said, before they get to that F4 fibrosis, which is cirrhosis.
08:55.365 --> 08:58.186
[SPEAKER_00]: And so that's something we think about a lot here.
08:58.606 --> 09:02.948
[SPEAKER_00]: I will also say that fibrosis progression is really dynamic.
09:03.128 --> 09:04.069
[SPEAKER_00]: It's variable.
09:04.609 --> 09:06.532
[SPEAKER_00]: some patients progress really fast.
09:06.692 --> 09:11.358
[SPEAKER_00]: Once they have, you know, develop mash, other patients progress more slowly.
09:11.378 --> 09:17.025
[SPEAKER_00]: And it is reversible, which is something that we'll talk about later on in this podcast.
09:17.688 --> 09:24.210
[SPEAKER_01]: I've also heard about the scoring system called Fib 4, and I know that can also help us risk stratify certain patients.
09:24.290 --> 09:25.891
[SPEAKER_01]: Can you tell us a little bit about that score?
09:26.331 --> 09:37.435
[SPEAKER_00]: Fib 4 is really what we use in a primary care setting to restratify these patients, basically determine who needs further work up.
09:37.775 --> 09:47.359
[SPEAKER_00]: It's telling us, based off of everything we just talked about with fibrosis, what's the probability that this patient in front of me has significant fibrosis?
09:47.740 --> 09:49.320
[SPEAKER_00]: And it's a validated score.
09:49.600 --> 10:01.646
[SPEAKER_00]: You can find it on any risk calculator that uses age, astalt and platelets to determine whether patients are likely to have significant fibrosis or not.
10:02.050 --> 10:11.958
[SPEAKER_00]: We don't use it for every single patient we see in our clinic, just to talk through which risk categories we think about using this score for.
10:12.278 --> 10:16.942
[SPEAKER_00]: We would use it if we think that we've caught mazzled incidentally.
10:17.443 --> 10:20.265
[SPEAKER_00]: So we think somebody has stytosis in their liver.
10:20.305 --> 10:23.568
[SPEAKER_00]: We want to see if they progress to mash with significant fibrosis.
10:24.188 --> 10:26.349
[SPEAKER_00]: then will definitely calculate a score.
10:26.369 --> 10:38.814
[SPEAKER_00]: When I say catch it incidentally, I mean that group of patients that we see stytosis when we get a liver ultrasound or some other form of imaging or patients that have elevated LFTs.
10:39.114 --> 10:43.776
[SPEAKER_00]: For those patients, we want to calculate a fib 4 because we think that they might have mass holes.
10:44.236 --> 10:46.737
[SPEAKER_00]: We want to determine if they have significant fibrosis.
10:47.407 --> 10:55.191
[SPEAKER_00]: There are also other groups that we search for Mazelden, because these are high risk groups with high pre-test probability of Mazelden.
10:55.271 --> 11:04.956
[SPEAKER_00]: And in terms of who's worth testing, everybody with type two diabetes, you wanna screen with a fifth four, and we'll talk about how to follow up on that.
11:05.317 --> 11:07.918
[SPEAKER_00]: Additionally, patients who have obesity,
11:08.558 --> 11:12.401
[SPEAKER_00]: And then one additional risk factor for metabolic syndrome.
11:12.721 --> 11:21.067
[SPEAKER_00]: And that might include elevated BMI, pre-diabetes, hyper-tension, hyper-tribosteridemia, or low-HGL.
11:21.267 --> 11:28.912
[SPEAKER_00]: For those patients with obesity and that one additional cardio metabolic risk factor, we tend to say, let's also scream them with a fit for.
11:29.393 --> 11:29.693
[SPEAKER_00]: Got it.
11:29.833 --> 11:30.153
[SPEAKER_01]: Okay.
11:30.253 --> 11:34.476
[SPEAKER_01]: So in our patient, I think you would definitely meet those criteria
11:37.754 --> 11:40.055
[SPEAKER_01]: obesity and hypertension in hyperlipidemia.
11:40.435 --> 11:48.177
[SPEAKER_01]: So, in his case, we calculate his fifth four score using his age, his AST, his ALT, and his platelets.
11:48.757 --> 11:51.338
[SPEAKER_01]: And we get a score of 1.55.
11:51.518 --> 11:52.999
[SPEAKER_01]: Can you interpret that for us?
11:53.539 --> 11:59.541
[SPEAKER_00]: Typically, when we interpret a fifth four, it's cut off on the lower end is 1.3.
11:59.641 --> 12:03.922
[SPEAKER_00]: So, anything below 1.3 means low probability of significant fibrosis.
12:04.362 --> 12:13.029
[SPEAKER_00]: It's cut off on the upper end is 2.67, so anything above 2.67 means high probability of significant fibrosis.
12:13.070 --> 12:25.940
[SPEAKER_00]: And when I say significant fibrosis, I'm really talking about F3 and F4, which are those stages of fibrosis for a patient with a mash, who have a lot of fibrosis, or ultimately cirrosis.
12:26.701 --> 12:29.606
[SPEAKER_00]: And so if you're below 1.3, we think you're in the safe zone.
12:29.646 --> 12:36.376
[SPEAKER_00]: If you're above 2.67, we think that you have a high probability of significant fibrosis of that F3 and F4.
12:37.315 --> 12:46.100
[SPEAKER_00]: The space in between 1.3 and 2.67 is really an intermediate space, and so those are patients that need further evaluation.
12:46.340 --> 12:52.383
[SPEAKER_00]: For this patient in particular, he's 64 years old, and so we can really apply this scoring.
12:52.403 --> 13:02.328
[SPEAKER_00]: And so when we see a 5th score of 1.55, we're thinking that they're in that intermediate phase and that they need more work up.
13:02.912 --> 13:07.555
[SPEAKER_01]: And any caveat to keep in mind with a patient's fib square when you get that initial number?
13:08.236 --> 13:14.781
[SPEAKER_00]: Yeah, the one brief pearl I would say is that, like we talked about, age is part of the scoring.
13:15.301 --> 13:26.409
[SPEAKER_00]: And so we tend to think that if somebody is 65 years older or older, we want to use different cut-offs here, rather than using 1.3 as our lower end, we tend to use 2.0.
13:31.142 --> 13:42.967
[SPEAKER_00]: Um, so if somebody has a fib four score of less than 2.0, then we say there's a low probability of significant fibrosis and that's really because fib four increases independent of age.
13:43.675 --> 13:59.773
[SPEAKER_00]: Similarly, if somebody is really young, though if they're less than 35 years old, there's some discussion among the hepatology community that you should think about it more closely for these patients because they're more likely to have a lower fit for.
13:59.893 --> 14:04.598
[SPEAKER_00]: So we don't use different cutoffs with that age group, but we just use more caution when we're interpreting it.
14:05.143 --> 14:05.383
[SPEAKER_01]: on it.
14:05.564 --> 14:11.269
[SPEAKER_01]: So back to our patient, his score was 1.55, which puts him in the intermediate risk category.
14:11.510 --> 14:14.272
[SPEAKER_01]: What exactly are our next steps in working him up?
14:14.733 --> 14:19.578
[SPEAKER_00]: So if they're in the intermediate risk category, we go to fibroscan next.
14:19.818 --> 14:25.364
[SPEAKER_00]: The fibroscan is called more formally, VCTE, vibration control,
14:27.566 --> 14:34.309
[SPEAKER_00]: And fibroscan is basically a fancy ultrasound at my hospital, the hepatologist and GI folks do it.
14:34.649 --> 14:37.910
[SPEAKER_00]: It's basically an ultrasound-based measurement of liver stiffness.
14:38.190 --> 14:41.731
[SPEAKER_00]: And liver stiffness is used here as a surrogate marker for fibrosis.
14:42.132 --> 14:47.994
[SPEAKER_00]: It's not perfect for patients with, you know, morbid obesity or a lot of hepatic congestion.
14:48.474 --> 14:50.995
[SPEAKER_00]: It can affect the quality of the fibroscan.
14:51.415 --> 14:55.959
[SPEAKER_00]: because those are conditions that limit the ultrasound wave penetration at the abdominal wall.
14:56.380 --> 15:02.305
[SPEAKER_00]: But it's a really good and well-validated test that can estimate essentially.
15:02.876 --> 15:11.478
[SPEAKER_00]: what the fibrosis score is and that serves as a proxy here for the stage of fibrosis that the patient is at.
15:11.618 --> 15:17.039
[SPEAKER_00]: So it will typically tell us that the patient is at 0, F1, F2, F3, F4.
15:17.319 --> 15:21.640
[SPEAKER_00]: There also is a second type of testing that I am not as familiar with.
15:21.660 --> 15:23.020
[SPEAKER_00]: We don't use it as my hospital.
15:23.060 --> 15:29.002
[SPEAKER_00]: It's called ELF testing and that's a proprietary blood test of three different components involved in matrix
15:30.182 --> 15:46.513
[SPEAKER_00]: and that can also be used for the risk stratify an intermediate fit for and they tend to use it a lot in rural settings where they don't have access to a fibroscan or sometimes you can also use it for patients with morbid obesity where the fibroscan is not as accurate.
15:46.846 --> 15:53.672
[SPEAKER_01]: Okay, just to recap, we have a patient who has mildly elevated LFTs, we think about their comorbidities.
15:53.752 --> 16:02.859
[SPEAKER_01]: We see that they have a paddock statuses on their imaging, so we take them through this primary risk assessment, and we calculate a fib 4, and in his case it was intermediate.
16:03.179 --> 16:11.486
[SPEAKER_01]: I don't think we touched on this yet, but if his fib 4 score were elevated, would we go on to the secondary risk assessment and do the fiber scan frame as well?
16:11.747 --> 16:28.188
[SPEAKER_00]: That's such a great question, and I would say it is definitely dependent on what your practices and what your access to hepatology is like, but I would say in general, we really only do the secondary risk assessment in that intermediate probability of significant fibrosis.
16:28.688 --> 16:31.331
[SPEAKER_00]: If they have a low probability, you don't have to worry about it.
16:31.371 --> 16:35.515
[SPEAKER_00]: You'll repeat that fit for every one to three years from here on out.
16:35.715 --> 16:44.744
[SPEAKER_00]: By contrast, if you have a high probability of significant fibrosis, so the fit for is telling you, you basically have F3 or F4 fibrosis.
16:45.045 --> 16:48.188
[SPEAKER_00]: You're going to straight refer them to hepatology, typically.
16:48.208 --> 16:51.992
[SPEAKER_00]: You don't even need that fibroscan to do that secondary risk assessment.
16:52.512 --> 17:09.440
[SPEAKER_00]: then you're stuck with that middle category for those patients with this intermediate or indeterminate risk of significant fibrosis, those are the patients that you're sending to you the fibroscan or you're sending them to do the ELF if you're in a role setting and that's what you use.
17:09.860 --> 17:15.423
[SPEAKER_00]: And then to break down what you see that would make you worried enough to refer to
17:17.744 --> 17:24.349
[SPEAKER_00]: Let's say going back to our patient, you have a fib four in that intermediate or indeterminate risk profile.
17:24.809 --> 17:27.511
[SPEAKER_00]: Their fib four is 1.3 to 2.67.
17:27.852 --> 17:30.173
[SPEAKER_00]: You send them, they get their fibro scan.
17:30.353 --> 17:37.218
[SPEAKER_00]: If the fibro scan shows 8 to 12 KPA, which is the way that it measures liver stiffness.
17:37.599 --> 17:43.103
[SPEAKER_00]: That is also considered intermediate oftentimes, but you want to refer those patients to
17:46.550 --> 17:47.711
[SPEAKER_00]: on that fibroscan.
17:48.252 --> 17:59.765
[SPEAKER_00]: If you're seeing greater than 12 KPA, a lot of liver stiffness, it portends significant fibrosis, and so you're also sending those patients to hepatology.
18:00.304 --> 18:09.646
[SPEAKER_00]: But by contrast, if you have one of these intermediate patients, going back to our patient, Mr. F, they've got a 5, 4 of 1.55, they do the fibroscan.
18:09.766 --> 18:12.886
[SPEAKER_00]: The fibroscan shows less than 8 KPA.
18:13.166 --> 18:18.047
[SPEAKER_00]: That really demonstrates that the patient does not have significant fibrosis.
18:18.167 --> 18:21.708
[SPEAKER_00]: They're in the F, zero to F, one range of fibrosis.
18:22.208 --> 18:27.569
[SPEAKER_00]: And so you can lump them back in with those patients, who have a fib four that's low risk.
18:27.689 --> 18:44.500
[SPEAKER_00]: because you're seeing that this patient has a low risk of significant fibrosis and for that sort of patient you don't need to refer them to see a hepatologist after you get the fibroscan you can just continue to measure the fit for and calculate that every one to three years along with your other low risk patients.
18:45.333 --> 18:50.537
[SPEAKER_01]: And is it possible to have an elevated fib for score even with normal LFTs?
18:51.038 --> 18:51.778
[SPEAKER_01]: Absolutely.
18:51.958 --> 18:55.161
[SPEAKER_00]: You can have an elevated fib for with normal LFTs.
18:55.401 --> 18:59.965
[SPEAKER_00]: For those patients, we really advise still using your clinical judgment.
19:00.185 --> 19:08.732
[SPEAKER_00]: If your patient is normal LFTs, but the fib for is elevated, which can happen, you still should get a secondary risk assessment.
19:09.432 --> 19:17.899
[SPEAKER_00]: if the fib-4 is in this indeterminate intermediate stage, and you should still refer to hepatology if the fib-4 is extremely elevated.
19:18.340 --> 19:30.770
[SPEAKER_00]: What constitutes clinical suspicion is really up to you, oftentimes those same patients that we were discussing earlier with metabolic syndrome or diabetes, they might have mazzled or mash,
19:31.250 --> 19:33.932
[SPEAKER_00]: without having elevated LFTs.
19:34.453 --> 19:42.319
[SPEAKER_00]: And so if those patients have a food for that falls into those buckets, we still recommend acting on it like normal.
19:42.800 --> 19:53.829
[SPEAKER_00]: By contrast, one question I get asked a lot actually is what else should I be doing if a patient is coming to me with elevated LFTs.
19:54.389 --> 19:56.811
[SPEAKER_00]: And I think that those are related to
19:59.994 --> 20:06.940
[SPEAKER_00]: If you really have a high clinical suspicion for mazzled as the eDology of the elevated LFT is, you don't have to do a ton.
20:07.260 --> 20:15.768
[SPEAKER_00]: I would say repeat the LFT is to make sure that they're actually elevated, but basically what we recommend is ordering a fibrous scan if it's appropriate.
20:16.008 --> 20:21.775
[SPEAKER_00]: You can also get hepatitis serology is an iron study is as just a very basic work up.
20:22.015 --> 20:31.187
[SPEAKER_00]: You also might get a liver ultrasound, although honestly if you're getting a fibroscan anyway, that can be helpful at pinpointing whether the patient has
20:31.747 --> 20:39.992
[SPEAKER_00]: Stiatosis or not, and so you can sometimes skip the liberal ultrasound if you know that the patient's going to get a fiber a scan pretty quickly.
20:40.813 --> 20:58.824
[SPEAKER_00]: And then if those elevated LFTs stay elevated for, let's say, three or six months with no clear diagnosis based off of that initial workup that you did, that's really when we recommend going to a secondary workup, which includes auto antibody studies like anti-LKM,
21:01.866 --> 21:11.139
[SPEAKER_00]: You could also get a surreal applause man to allow Wilson's disease, you could get an alpha, one anti-tripson, and so you're just doing the broader workup at that point.
21:11.600 --> 21:15.846
[SPEAKER_00]: The one exception I would say is that if a patient has ALT or...
21:16.407 --> 21:19.708
[SPEAKER_00]: AST that's greater than five times the upper limit of normal.
21:19.828 --> 21:21.128
[SPEAKER_00]: You really do want to do that.
21:21.188 --> 21:25.029
[SPEAKER_00]: Full work-up, including the autoimmune markers, right away.
21:25.290 --> 21:31.331
[SPEAKER_00]: Masks will not cause an AST ALT greater than five times the upper limit of normal.
21:31.351 --> 21:36.453
[SPEAKER_00]: Typically, and so if you see that, it's a reason to pause and really focus on a broader work-up.
21:36.693 --> 21:37.313
[SPEAKER_01]: Okay, great.
21:37.913 --> 21:48.197
[SPEAKER_01]: So, let's say that Mr. F gets the fiber scan, his score is 11 KPA, which again is in this intermediate risk category of 8 to 12.
21:48.657 --> 21:51.238
[SPEAKER_01]: This tells us that he should see hepatology.
21:51.478 --> 21:58.520
[SPEAKER_01]: We send him to hepatology, they take a look at his case, and given that he has several risk factors that could lead to fibrosis.
21:59.068 --> 22:04.517
[SPEAKER_01]: Like we spoke about before, his obesity, his hypertension, diabetes, hyperlipidemia.
22:04.657 --> 22:07.923
[SPEAKER_01]: They think that a biopsy is not necessary for him.
22:08.686 --> 22:13.851
[SPEAKER_01]: So, Mr. F asks the hepatologist what he can do to reduce his risk of progression.
22:14.131 --> 22:16.933
[SPEAKER_01]: Can you tell us a little bit about the treatment of Masold here?
22:17.494 --> 22:18.515
[SPEAKER_00]: Yeah, absolutely.
22:18.875 --> 22:26.742
[SPEAKER_00]: I would say, you know, the goal of the treatment here is really like I said, not to sound like broken record, but it's to prevent cirrhosis.
22:27.223 --> 22:34.229
[SPEAKER_00]: And also to prevent cardiovascular disease, because liver fibrosis and mazzled and mash, they're just one
22:34.849 --> 22:40.414
[SPEAKER_00]: part of this broader metabolic syndrome and this broader slate of cardiovascular metabolic disorders.
22:40.974 --> 22:49.100
[SPEAKER_00]: And so in order to achieve those goals, the cornerstone of treatment is oftentimes non-pharmacological for these patients.
22:49.721 --> 22:52.463
[SPEAKER_00]: We really, really, really want them to lose weight.
22:53.063 --> 23:01.650
[SPEAKER_00]: And in addition to thinking about non-pharmacological ways to lose weight, there's now obviously so much on the market and so many tools that we have in our arsenal.
23:02.250 --> 23:05.291
[SPEAKER_00]: to, you know, help patients lose weight in other ways, too.
23:05.811 --> 23:16.813
[SPEAKER_00]: I really hammer home weight loss with these patients because if you have even a 5% reduction, there are proven studies that show that you have less stytosis in your liver as a result.
23:16.853 --> 23:21.815
[SPEAKER_00]: So let's say you lose 5% of your body weight, you're going to lose fat in the liver, too.
23:22.115 --> 23:26.376
[SPEAKER_00]: And if you have 7 to 10% loss of body weight, then
23:28.526 --> 23:35.249
[SPEAKER_00]: complicated by fibrosis, we actually see a reversal of fibrosis and fibrosis reduction.
23:35.750 --> 23:39.011
[SPEAKER_00]: And so weight loss is absolutely the cornerstone of this.
23:39.672 --> 23:48.556
[SPEAKER_00]: Non-pharmacologically we tend to think about a Mediterranean diet, all of the lifestyle and dietary counseling that we tend to do around minimizing process meets.
23:49.076 --> 24:02.428
[SPEAKER_00]: ultra-processed foods, sugar-sweetened beverages, recommend physical activity, greater than 150 minutes a week of moderate intensity, physical activity, or 75 minutes a week of vigorous physical activity.
24:02.568 --> 24:06.611
[SPEAKER_00]: And we also counsel avoiding alcohol in particular.
24:06.631 --> 24:12.917
[SPEAKER_00]: There's actually no safe level of alcohol use for their literature in these patients, so we counsel a lot around that.
24:13.377 --> 24:27.939
[SPEAKER_00]: We use a lot of GLP1 agonists in my practice and also GLP1GIP at dual agonists, and so those are very, very exciting and more to come in that pharmacological area as well, I think.
24:28.339 --> 24:32.982
[SPEAKER_00]: We additionally tend to refer a lot of our patients for bariatric surgery.
24:33.482 --> 24:38.505
[SPEAKER_00]: If they meet criteria at the hospital that I work at, we have a really, really strong bariatric program.
24:38.906 --> 24:44.189
[SPEAKER_00]: And so that can be also very helpful for this disease too if the patient is motivated and interested in that.
24:44.789 --> 24:54.455
[SPEAKER_00]: And then I think we'll talk about this in just a second, but there's also one FDA approved drug that I don't prescribe myself, but the hepatologists do prescribe in terms of treatment as well.
24:55.101 --> 25:00.764
[SPEAKER_01]: I actually just saw a commercial for this when I was at the gym recently and I had never heard of it before.
25:00.824 --> 25:03.225
[SPEAKER_01]: So yes, please do tell us about this medication.
25:03.245 --> 25:04.966
[SPEAKER_00]: Okay, that's so funny.
25:05.227 --> 25:07.588
[SPEAKER_00]: I have yet to see a commercial on it, but I love that.
25:07.748 --> 25:11.530
[SPEAKER_00]: I'll just say, you know, I know there's so much drug advertising out there, but this medication
25:11.930 --> 25:14.291
[SPEAKER_00]: actually is supposed to be quite good.
25:14.671 --> 25:15.831
[SPEAKER_00]: It's called resmitterom.
25:16.132 --> 25:21.193
[SPEAKER_00]: It's the first FDA approved medication for treating mazzled and mash.
25:21.433 --> 25:32.397
[SPEAKER_00]: It is a THRB receptor agonist, which is a class of drugs that basically promote fatty acid oxidation and increase mitochondrial respiration, which reduces hepatic fat accumulation.
25:32.737 --> 25:35.398
[SPEAKER_00]: It demonstrated on studies that there was
25:40.940 --> 25:44.022
[SPEAKER_00]: to reverse fibrosis for mash and mazzled.
25:44.083 --> 25:51.568
[SPEAKER_00]: And so Resmeteram is very exciting for patients in particular who have F2 or F3 fibrosis.
25:51.848 --> 26:07.760
[SPEAKER_00]: Those are really the stages where we think it works, where the patient has enough fibrosis to qualify for Resmeteram and to need that fibraotic reversal, but not so much that they've entered the stage of F4 fibrosis or Cerosis.
26:08.380 --> 26:13.102
[SPEAKER_01]: That is very exciting, you know, this is an area that hasn't really had a lot of dedicated medications for it.
26:13.162 --> 26:15.663
[SPEAKER_01]: So, very exciting things to come there.
26:15.944 --> 26:23.807
[SPEAKER_01]: We are nearing the end of our episode, but before this patient's appointment is over, he has two more questions for our epitologist.
26:24.227 --> 26:26.868
[SPEAKER_01]: The first is that he's on a tour of a statin.
26:26.888 --> 26:30.310
[SPEAKER_01]: He's heard that these statin medications can be tough on the liver.
26:30.690 --> 26:34.652
[SPEAKER_01]: So he just wants to make sure that it's safe for him to continue staying on a tour of a statin.
26:35.703 --> 26:36.723
[SPEAKER_00]: Yeah, absolutely.
26:37.204 --> 26:38.524
[SPEAKER_00]: Stay on a tour of a statin.
26:38.624 --> 26:46.727
[SPEAKER_00]: Like we were talking about, Mazel just one part of this greater spectrum in this greater disease area of metabolic syndrome.
26:47.488 --> 26:53.290
[SPEAKER_00]: And so preventing those cardiovascular events is very, very important in that population.
26:53.330 --> 26:56.071
[SPEAKER_00]: And so definitely stay on the tour of a statin.
26:56.431 --> 27:11.261
[SPEAKER_00]: What I will say is, again, I am not a prescriber of resmitterum, the hepatologist that my institution prescriber, but I will just say it does have drug interactions for resubis statin and symbestatin if somebody's on resmitterum concurrently.
27:11.281 --> 27:14.663
[SPEAKER_00]: They'll cap the dose for those statins at 20 milligrams.
27:15.103 --> 27:20.307
[SPEAKER_00]: If somebody's on private statin or a tourist statin, they'll typically cap the dose at 40 milligrams.
27:20.347 --> 27:21.888
[SPEAKER_00]: And the idea there is just
27:22.386 --> 27:24.867
[SPEAKER_00]: to prevent any drug drug interactions.
27:25.688 --> 27:26.488
[SPEAKER_01]: Got it, makes sense.
27:26.888 --> 27:34.531
[SPEAKER_01]: And you were starting to get at this before with regard to alcohol, but he does like to go out with his friends a couple times a week and get a few beers.
27:34.832 --> 27:36.132
[SPEAKER_01]: What would you tell him about that?
27:36.432 --> 27:41.795
[SPEAKER_00]: Yeah, what I would say is, unfortunately, there's really no safe amount of alcohol in tea.
27:42.215 --> 27:46.137
[SPEAKER_00]: When it comes to Masold and Mash, there was actually a 2010 study.
27:47.352 --> 27:58.396
[SPEAKER_00]: from Scotland that showed that alcohol intake is actually super additive to the effects of increased BMI and mazled on a patient.
27:58.457 --> 28:03.979
[SPEAKER_00]: And so we think that alcohol can really accelerate the risk and progression of mazled and mashing.
28:04.039 --> 28:07.420
[SPEAKER_00]: So definitely want to counsel against that if possible.
28:07.740 --> 28:08.100
[SPEAKER_01]: Great.
28:08.361 --> 28:12.502
[SPEAKER_01]: Our patient is counseled on all of these things, including weight loss efforts.
28:12.522 --> 28:14.143
[SPEAKER_01]: He actually decides to start a GLP1.
28:15.092 --> 28:19.678
[SPEAKER_01]: and they plan to follow up again with repeat labs and imaging in around a year or so.
28:20.439 --> 28:29.029
[SPEAKER_01]: Dr. Sanders, thank you so much for helping us take such good care of our patients in the primary care setting and learning when to refer them to hepatology.
28:29.629 --> 28:30.250
[SPEAKER_01]: Such a pleasure.
28:30.270 --> 28:31.832
[SPEAKER_01]: I think so much for having me on today.