Special Edition - Metabolic Dysfunction-Associated Steatohepatitis (MASH) - Part 3 - Cases, Jan 2026

Summary

Diabetes Core Update – Special Edition: MASH Part 3 – Cases Jan 2026

Podcast Date: February 17, 2026
Host: Dr. Neil Skolnick
Guests: Dr. Alina Allen (Mayo Clinic, Hepatology), Dr. Susan Kucera (Jefferson Health, Family Medicine)
Podcast Focus: Clinical case-based discussion on Metabolic dysfunction Associated Steatohepatitis (MASH), screening practices, diagnostic challenges, and management strategies, specifically oriented toward the needs and realities of primary care.

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Episode Overview

This episode, the third of a special three-part series, takes a case-based approach to integrating the latest guidelines, diagnostic tools, and evolving treatments for MASH (formerly known as NAFLD-related steatohepatitis). The conversation addresses real-world issues in screening, risk stratification, and management, with a particular focus on helping primary care clinicians adapt to an increasingly complex landscape. The dialogue draws on both hepatology and primary care perspectives, aiming to give practical, usable guidance for frontline providers.

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Key Discussion Points

1. The State of MASH Screening & Primary Care Realities

[03:27]

• Scope of the Problem:
  • Prevalence of MASLD (the precursor to MASH): 30% of adults, up to 65% of patients with T2DM in the US.
• Screening Recommendations Recap:
  • Should screen those with overweight/obesity + metabolic risk factors, all patients with T2DM, or elevated LFTs.
  • Main goal: Identify MASH with advanced fibrosis (F2/F3), where intervention can have a meaningful impact.
• Primary Care Uptake:
  • Dr. Kucera notes screening is "not something that's happening regularly" ([04:15]), with most diagnoses in practice arising from incidental findings (e.g., LFTs on routine panels or imaging for unrelated issues).
• Barriers in Primary Care:
  • Overwhelming number of things to screen for in diabetic patients (A1c, B12, microalbumin, eye/foot exams, heart failure, etc.); hard to “add one more thing.”
  • “If we're going to impact overall longevity, morbidity, mortality, we've got to add it to the list.” – Dr. Kucera ([05:53])

2. Case 1: The Asymptomatic At-Risk Patient

Case Details:

• 55-year-old male, 10 years T2DM, obesity, hypertension, hyperlipidemia.
• LFTs normal; AST 33, ALT 37, platelets 155.
• Routine FIB-4: 1.93.

FIB-4 Interpretation and Next Steps

[07:13]

• FIB-4 Cutoffs:
  • <1.3 = low risk; >1.3 = evaluate further (generally via liver stiffness measurement).
  • Age sensitivity: For those 65+, the cutoff is 2.0.
• Diagnostics After FIB-4:
  • Primary care commonly orders an elastography-based test (e.g., FibroScan).
  • Newer, more accessible tests: ELF (Enhanced Liver Fibrosis) test, a blood-based tool.
    • Caveat: Exact actionable cutoffs are evolving, but current guidance is ELF ≥9-9.5 signals need for further evaluation ([08:16], Dr. Allen).
    • Pros: May assist where elastography is unavailable, or when patients struggle with follow-up appointments.

Practical Considerations

[10:28]

• Tests are probabilistic, not binary—require clinical judgment.
• Not all patients in practice will follow-up on extra imaging orders; convenience of blood-based options is valuable in some populations.
• “Cutoffs always need to be used with clinical judgment.” – Dr. Skolnick ([10:28])

Elastography Results & Clinical Integration

• Elastography <8 kPa:

  • Low risk for advanced fibrosis.
  • Management: Lean into metabolic risk reduction, lifestyle, and rescreen in 1-2 years (timing individualized to risk) ([14:41], Dr. Kucera).

• Platelet Nuances:

  • Platelet count of ~155 may be “normal,” but warrants attention—could signal more advanced disease despite normal function tests ([15:56], Dr. Allen).
  • Always assemble the big picture, not just isolated test results: “Liver disease estimation is a puzzle, the pieces … put together in a nice symphony.” ([17:31], Dr. Allen)

If Elastography ≥8 kPa or ELF ≥9.2

[18:43]

• Indicates clinically significant fibrosis (stage 2 or higher).
• Next: Rule out cirrhosis (use imaging—CT, ultrasound—for morphology and look for portal hypertension, splenomegaly, and check platelets).
• If cirrhosis is excluded, initiate treatment for moderate-advanced fibrosis MASH.

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3. Case 2: Patient With Mild LFT Elevations

Case Details:

• 61-year-old woman, obesity, hypertension, hyperlipidemia, prediabetes.
• On atorvastatin and lisinopril, A1C 5.9, AST 62, ALT 70, normal AlkPhos and bilirubin, platelets 155.
• FIB-4: 2.92.

[21:37]

• Common, complex presentation:
  “We see this at least once a week, maybe more. This is how we tend to stumble upon metabolic associated liver disease...” – Dr. Kucera
• Differential diagnosis is broader:
  • Consider statin effect, viral hepatitis, other medications, autoimmune liver diseases, hemochromatosis, in addition to MASLD/MASH.
• Initial Workup:
  • Exclude other chronic liver disease (especially viral hepatitis, alcohol use).
  • Non-invasive fibrosis assessment if available; otherwise refer to hepatology.
• Primary Care Role:
  • If tools are available, pursue noninvasive staging before referral.
  • Hepatology prefers patients to arrive with chronic liver disease exclusions and noninvasive fibrosis assessment; allows for more targeted care ([23:02], Dr. Allen).

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4. Evolving Treatment: What’s Available Now and What’s Coming

[26:01]

• Two FDA-Approved MASH Medications (2024 & 2025):

  • Resmetirom (Resdifra):
    • Thyroid hormone mimetic, liver-directed, weight-neutral, improves steatosis/inflammation/fibrosis, also reduces LDL.
  • Semaglutide (Wegovy):
    • Familiar to primary care, approved for MASH with moderate/advanced fibrosis, also indicated for weight loss and T2DM. Multiple metabolic benefits.
  • Effectiveness: Roughly similar; side effects mainly GI in nature.
  • Patient-centered choice: Consider comorbidities, coverage, and patient priorities.
  • “In primary care … you can either use [semaglutide] … for the liver indication.” – Dr. Allen

• In the Pipeline:

  • More GLP-1 agents (retatutride, tirzepatide), dual-acting agents, FGF21 agents, all in phase 3 trials.

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5. Special Considerations: Cirrhosis

[31:15]

• Why care about cirrhosis before starting MASH-directed therapy?
  • No phase III data or FDA approval for these drugs in MASH-cirrhosis.
  • Not contraindicated if indicated for diabetes/obesity, but be cautious about risk for sarcopenia and frailty:
    • Counsel on protein intake and resistance exercise ([31:15], Dr. Allen).
• Diagnosing Cirrhosis:
  • High elastography values: FibroScan ≥12-15 kPa, MRE ≥4.6-5 kPa, ELF ≥11.3.
  • Use imaging (US/CT) to detect nodular liver, spleen size, and portal hypertension.
  • Platelet count, FIB-4, and imaging—“constellation of findings.”

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Notable Quotes & Memorable Moments

• On Barriers to Screening:

  “Primary care, the things we need to screen for—that list is like, longer by the minute… sometimes it's really hard to add one more thing to the list.”
  — Dr. Susan Kucera ([04:59])

• On Test Interpretation:

  “We often think of tests as binary… they're not. They're all probability based. And I love the way that you discussed that…”
  — Dr. Neil Skolnick ([10:28])

• On Platelets as a Clue:

  “Platelets have a very strong voice when it comes to fibrosis estimation. Although [a] platelet value of 155 may be considered normal, it always catches our hepatology eye...”
  — Dr. Alina Allen ([15:56])

• On Multimodal Assessment:

  “Liver disease estimation is a puzzle. It's the pieces that have to be put together... platelets are a big part of that symphony…”
  — Dr. Alina Allen ([17:31])

• On the Excitement for New Therapies:

  “It is a very exciting time for hepatology… we have two drugs and… several in the pipeline… for liver disease if they prove their safety and effectiveness.”
  — Dr. Alina Allen ([26:01])

• Vision for the Future:

  “My hope… is that liver will need to deserve its own space, just like the eyes and the kidneys and the nerves… that we will celebrate this achievement in the next few years—is liver is a quality measure in patients who have diabetes.”
  — Dr. Alina Allen ([34:51])

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Important Timestamps

• Introduction, importance of MASH – [00:02]
• Barriers to screening in primary care – [04:59]
• Case 1: FIB-4, ELF, and age-related interpretation – [07:13]
• Factoring in platelets and “test symphony” – [15:56], [17:31]
• Elastography thresholds and re-screening intervals – [14:41]
• Case 2: Mildly abnormal LFTs, workup approach – [21:37]
• Current and upcoming treatments – [26:01]
• Cirrhosis: why and how to rule out – [31:15], [33:10]
• Dr. Allen’s vision for liver as a quality measure in diabetes care – [34:51]

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Final Takeaways

• Screening for MASH with modern risk tools should become routine, especially in T2DM and those with metabolic syndrome.
• Diagnostics must be tailored: Use age-appropriate FIB-4 cutoffs, leverage ELF where imaging is impractical, and always view all labs/imaging in the context of the whole patient.
• Platelet count “gray zone” demands nuance and may signal a need for more aggressive assessment.
• Treatment for MASH is real and expanding: Resmetirom and semaglutide are options for moderate-to-advanced fibrosis. Watch for new approvals.
• Don’t treat blindly—exclude cirrhosis before initiating MASH-targeted drugs.
• Primary care clinicians need practical, streamlined pathways and should collaborate with hepatology when feasible.
• The future will position liver health alongside kidneys, eyes, and nerves as a quality surrogate in diabetes management.

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For more information:
Visit www.diabetesjournals.org

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[End of Summary: Covers Core Content, Clinical Pearls, Cases, and Actionable Guidance]

Transcript

[A]

Welcome to this special three part series of Diabetes Core Update where we are going to discuss metabolic associated liver disease, that is mash. And this is important because the prevalence of MASH has increased over the last 30 years, has direct consequences on both quality of life and a range of health outcomes. It's one of the leading causes of end stage liver disease requiring transplant. Approximately 30% of adults, as many as 65% of individuals with type 2 diabetes in the United States have metabolic dysfunction associated steatotic liver disease, which is the precursor to MASH. I'm your host, Dr. Neal Skolnick, professor of Family and Community Medicine at the Sidney Kimmel Medical College of Thomas Jefferson University. This special series of Diabetes Core Update is sponsored by by Baringer Ingelheim. We've discussed in the first episode the epidemiology of mesh. We discussed how mast cell progresses, the consequences of mesh. We discussed screening for MESH and particularly for advanced stages of mash. In the second episode we discussed treatment. And in this third episode we're going to bring it all together with some cases. Joining us for today's episode are two master clinicians. One is a liver specialist, the other a primary care physician. Let me first introduce Dr. Alina Allen, who you met on our second episode. Dr. Allen is an Associate professor of medicine at the Mayo Clinic in Rochester, Minnesota. She serves as director of Hepatology and director of the Masold Clinic. She is a physician scientist with an NIH funded research program that focuses on improving outcomes in people with metabolic dysfunction associated steatotic liver disease. And she is an associate editor of the journal Hepatology. We work together on a clinical care pathway for risk stratification and management of patients with metabolic dysfunction associated steatotic liver disease that is coming out in the near future in the journal Gastroenterology. And it is a clinical care pathway that is really. Alina, as we've talked about a number of times, focused on trying to help people like sue and I, primary care clinicians, really be on top of and know what to do with MASLD and mash And Alina, welcome back to the ada's podcast.

[B]

Hi Neil, thank you for having me back. I'm very happy to keep the discussion going.

[A]

Thanks so much. And our Next guest is Dr. Susan Kucera. Dr. Kucera is the program Director of the Jefferson Health Abington Family Medicine Residency Program and an Associate Clinical professor of Family and Community Medicine at the Sidney Kimmel Medical College of Thomas Jefferson University. Sue, also welcome. You've been on this podcast many times. Welcome back.

[C]

Oh, I love this podcast, I can't wait to go through these cases. It should be really educated.

[A]

Yeah. In the first podcast of this series, we talked to Dr. Jay Shuberg about screening. Briefly, to recap, when we think about screening, we should be screening people with overweight or obesity and an additional metabolic risk factor. We ought to be screening people with type 2 diabetes and people with elevated LFTs. And our goal with that screening is to identify people with MASH who have advanced fibrosis, specifically F2 or F3, because intervention there can make a difference by slowing progression and even reversing fibrosis for many people. Sue, what is your sense? Do you think screening for MASH is well appreciated and carried out in primary care? Right now?

[C]

The short answer is no. Right. So when we think about screening, we're thinking about an asymptomatic patient that we're trying to identify a disease in. And I don't think that this is something that's happening regularly.

[B]

Right.

[C]

I think most of us see an awful lot of metabolic associated liver disease, but most of the time we're finding this. They have slightly abnormal LFTs. They had imaging for another reason. And we find this on an incidental imaging study. You know, I don't think we're doing that typical asymptomatic patient screening like we should be.

[A]

Yeah, and that's my sense as well. And we talked just a couple of minutes ago about how common this is.

[B]

When.

[A]

Why do you think we're not screening for it?

[C]

Well, gosh, you know, primary care, the things we need to screen for. That list is like, longer by the minute. Right. Even, you know, think about a patient who has diabetes. Right. 60% might have metabolic associated liver disease. But you know, in primary care, where I'm looking at their A1C, their CMP, their lipid, did we do a B12? Cause they're taking metformin. Is there microalbuminuria done? Did they have their eye exam, their foot exam, their immunizations? Now we have to screen them for heart failure. Right. Like, there are so many things that I think sometimes it's really hard to add one more thing to the list. But, you know, as we're going to get into with the therapeutics that are out there now and how prevalent MASH has become, this is really, really important. And I think if we're going to impact overall longevity, morbidity, mortality, we've got to add it to the list. It's gotta be something we start thinking about.

[A]

Yeah, I agree with you. And you know, it's interesting. I've always feel that primary care has a great sense of rele. And even though the screening recommendation has been out there for a while, until there was clear treatment, a clear path forward to help people, you can make an argument that while this would be good to know what is going to be the impact, but that argument no longer is anywhere near reasonable because as Alina, you talked about in the second episode, as we'll touch on later today, there's a lot we can do now. So let's jump into some cases. And for our first case we'll take that of a 55 year old male with a 10 year history of type 2 diabetes, obesity, hypertension and hyperlipidemia. Not at all unusual. He has normal liver function tests, his AST is 33, ALT is 37, platelets 155. Nothing here is jumping out at us, which is just why. Right. Screening becomes so important. His physician does a fib 4 as a part of routine screening and it calculates out to 1.93. Sue, can you discuss how to interpret the fib score and the next steps for this patient?

[C]

Right, so you know, this patient, we look at their age, you know, less than 65, and our fib 4 is 1.93. So we know in our head that 1.3 is the cutoff. And you know, lucky for us, a lot of electronic records actually like pop this into your note if you're doing the calculation. But 1.3 or less is considered, considered normal. Anything over 1.3 needs some further evaluation. And I think for the most part, I think those of us in primary care, we're looking for some sort of measure of liver stiffness through ultrasound, usually a transient elastography, usually a fibroscan. I think that's what we're commonly ordering and used to ordering in these instances. Although, I mean, there are new tests now there's a new test called an ELF test which might be a little more accessible for patients. But again, I think availability, indications, insurance coverage, I think that's still a little bit of a black box for us in primary care. Alina, how do you weigh in on this, on how we might be able to use this in our primary care practices?

[B]

I think that having a new tool in the toolbox that is a blood based tool is always welcome. And I think patients would agree and primary care physicians or frontline physicians would agree on that. So ELF is a relatively new but not very new test, is short for enhanced liver fibrosis test, and it's a proprietary one that was designed to detect fibrosis, liver fibrosis, and it can be used. The accessibility is not as wide as the routine blood test like a biochemical panel, for example, but there could be pockets of the country or states where a fibroscan or elastography by ultrasound or Mr. May not be available. And exploring whether the ELF is an option I think is a good idea and it's good for primary care physicians to know. The fact that it's newer means that we are still figuring out the exact cutoff based on which we need to do something. So what's an actionable level or value is still a little bit in flux. I think the initial guidances used a cutoff of 7.7 that with time we learned was maybe too low. So the updated guidances I think will increase that. And based on some more recent studies, the cutoff would be something around 9.2, 9.54 or 9. So maybe we should remember something around 9 or higher or 9.2 or higher where something needs to be done. And that something is second line testing, which again kind of gets back into elastography, but at least it's maybe a better first line screening or more accessible maybe if elastography is not available immediately after a fib four.

[A]

Yeah. You know, as I listen to you, two things come to mind. One, we often think of tests as binary. When we casually think about them, they're not. They're all probability based. And I love the way that you discussed that. Sometimes our understanding of a test evolves and we try to hone in on what the right cutoffs are. But those cutoffs always need to be used with clinical judgment. The other thing that I've just started ordering the ELF recently and my sense is not even just for areas of the country where elastography isn't available. In our hospital it is. We're outside of Philadelphia. But it's just so much more convenient for patients. And I have some patients that I know are not very good at following up to get tests that require a separate appointment. And I've started ordering the ELF for that group and you know they're going to get their A1C done or their complete metabolic panel anyway. And that then lets me further risk stratify. And if I really feel I need elastography, then I emphasize that they get it done. But not all of my patients are perfect. So Alina, the other thing I want to touch on because when it comes to cutoffs and understanding tests, the FIB4 is affected a lot by age. In that way, it's not that different than the ASCVD calculator that we're really used to. And can you remind us of whether we ought to be taking age into account in our algorithm for the fib4 if someone's over 65 and why that's so?

[B]

Yes, that's a very important point. The FIB4 calculation includes age, AST, ALT and platelets. And there are quite a few studies that have unequivocally shown that the age component of it limits its performance a bit. What does that mean at extremes of ages? By extremes we mean younger than 35, so not that extreme. For an adult population or older than 65, the performance lowers a bit in its prediction for advanced fibrosis estimation. Remember, fib 4 has been developed for stage 3 to 4 fibrosis. So what do we do? We can adjust for the 65 or older age cutoff to increase that point of 1.3 to 2. So for our adult population of patients who have an age of 65 or older age, older, older, the action point will be Fib4F2 or higher. We don't really have such a quick fix for our younger population. So younger than 35. All I would say is take it with a grain of salt. If the clinical suspicion is quite high that this patient may have advanced fibrosis. And unfortunately we do see advanced fibrosis and even cirrhosis in people who are young, even in kids in that group. I would not base any action or decision on a fib 4 other than yes, you can calculate it and kind of get a sense, but if it's normal, it does not rule out advanced fibrosis in those young people. And I would rely on other non invasive tests or go straight to a histography if the clinical suspicion is high, especially if they have diabetes, long standing comorbidities for metabolic dysfunction and so on.

[A]

Really important points on both ends of that age spectrum. Because we don't want to be over sending people for tests in the old group or under hitting it in the young group. So, sue, you've ordered transoneelastography on the patient we just described. It comes back with the value of 6 Kpa. Now, KiloPascal is not a unit even we're interested in in primary care. What do you do at that point?

[C]

Yeah, it's helpful. And you know, this is where just knowing where to find your algorithms in primary care becomes really, really important. But the number here that we're looking for is 8. So less than 8kpa is low risk for fibrosis. That's not to say though that we just ignore these patients. Right. So I think we really start to lean in to all of our metabolic risk reduction strategies. Right. We know that having metabolic associated liver disease increases your metabolic risk in all other areas of metabolic risk. And so less than 8, you can lean into your lifestyle strategies, your metabolic risk reduction and then consider screening them again somewhere between one and two years. And I would say for me that will one to two years depends on, you know, their risk. Right. Like how many metabolic associated risk factors do they have? They might get screened sooner rather than later. So 1 to 2 years. This also applies if their fib 4 is less than 1.3. You should also lean into your strategies and consider screening them again in another one to two years. So just keeping that in mind that this isn't a once and done that we want to keep this on our radar.

[A]

That's so important. Alina, any thoughts there?

[B]

I completely agree with sue about revisiting in the future. The Beauty of Fib 4 Easy Calculatable Blood Test is that you can always reassess a year later. It's a little bit harder with elastography or other techniques that require specific ordering or other tests. So one to two years is a really reasonable timeframe to reassess. I have to put my hepatology hat for millisecond in this case. Platelets have a very strong voice when it comes to fibrosis estimation. Although platelet value of 155 may be considered normal, it always kind of catches our hepatology eye because unless the patient really lives in those values, then that could be a sign that maybe we need to consider another non invasive test to really confirm the low risk of advanced fibrosis. So this is kind of going into the little cracks of a case and maybe a rabbit hole. But 155 should kind of raise our antennas a bit and just make sure that we trust the non invasive test that's so important.

[A]

I'm so glad you raised that. And that probably becomes very important in those people who are a bit younger, you know, even 40, 45, that this is very age dependent. So if you see that recognizing tests are not biase binary, they're probability based. And that's really a helpful pearl. Thank you.

[B]

Then the other population to consider would be in people where maybe fibroscan may be not as accurate. For those who have a high waist circumference, there may be a little bit of lower performance There or accuracy. So again, just. I always describe liver disease estimation as a puzzle. It's the pieces that have to be put together. So never just look at one piece such as fib four or one or the other. Look at all do they come together in a nice symphony. So platelets are a big part of that symphony, which is why I mentioned that. So everything has to be taken with a grain of salt. If things do not match nicely.

[A]

Boy, that's interesting. I had not thought a lot about that. And that's so important things like. And maybe we'll come back to it later. If you're fib is very high and your elastography is not worrisome, that's an alert. Now, Alina, let's say we ordered in this patient a liver function test and it returned instead of at a value of 6, a value of 9.5. How do we proceed at that point?

[B]

A value of 9.5 is above 8, which is that number that sue mentioned before and will be very important to remember. Just like the 1.34 fib4. So that raises the suspicion for fibrosis, at least clinically significant fibrosis, which is stage two out of the four stages by histology or higher. So something needs to be done that means that this patient with multiple risk factors for mesh and if they are specifically they're long standing, that means that that was sufficient enough to create some fibrosis in the liver. So this is the patient we need to think treatment and how do we treat? We can either talk about that now or we can go later into this topic. But again, if the pieces of the puzzle all fit together, this is something where something needs to be done. We do have therapies now that are specifically approved for MASH with moderate to advanced fibrosis, which is a zone of middle range, not mild, not cirrhosis, but right in the middle, which is where this pat would fit. So we can again, we can get into those. We don't have anything approved for cirrhosis. So one other caveat here before we consider treatment with a MASH indication would be to look at the other pieces of the puzzle to make sure that this is not actually cirrhosis. It is possible that sometimes patients with cirrhosis have a lower liver stiffness measurement, especially with those platelets of 155. Do we have any cross sectional imaging to exclude a nodular appearing liver surface or splenomegaly, other signs of portal hypertension and so on. So if these criteria are met, meaning that the VCT is above 8 and we can safely say the patient doesn't have cirrhosis. The next thing would be to consider treatment for mesh with moderate to advanced fibrosis.

[A]

You know, let's come back to treatment as you suggested, in a little bit. And I want to make sure we remember because it's no secret that one of the treatments out there are GLP1, specifically semaglutide as FDA approved, that we, that we are attentive to ruling out cirrhosis and how to do that in a little bit. Let's first jump into our second of our two cases though, and this is a 61 year old woman with obesity, hypertension, hyperlipidemia and pre diabetes. She's on atorvastatin for her hyperlipidemia and lisinopril for her blood pressure. She has an A1C of 5.9, mildly elevated LFTs, an AST of 62, an ALT of 70. She has an normal alk fast normal bilirubin platelets, again of 155. Her fib 4 comes out to 2.92.

[C]

Sue, this case happens all the time, right? So if we're being honest, we see this at least once a week, maybe more. And this is how we tend to stumble upon metabolic associated liver disease, right? This case is different than the previous case because our LFTs are mildly elevated. And we need to remember that not all LFT elevations is metabolic associated liver disease, but a lot of it is, right? So I think we just need to put our primary care hats on, broaden our differential and realize that MASH is very common. Very likely, but this could be a lot of other things, right? It could be her statin, it could be something like hepatitis, other medications, autoimmune disease, hemochromatosis. Right? All of these things should be on our list. Her Fib 4 is high, but, you know, and I think Alina will probably help us tease that out. You know, hard to know what that means and in this patient, but she definitely needs more of a workup, right? This is something we work up all the time. Definitely needs more labs, probably needs some imaging. Alina, as the, you know, the expert here, I would love to know, you know, what, what is your algorithm? Cause I think I see this done a lot of different ways in primary care. The amount of labs we order, does everyone get a traditional ultrasound? What imaging are we doing? So I would love to hear like, you know, what would be your perfect workup for this patient?

[B]

Thank you. Yes, I think this is the Classic presentation for mash. Right. You have a little bit of an alert from the abnormal liver enzymes. Again, platelets155, a lot of risk factors. So why not mash? Right. This is most likely because that's the most common cause of chronic liver disease. So if we were to just guess that's what it is. But I completely agree that we should not just assume that this is what it is and maybe sent to hepatology. I think doing due diligence to exclude other liver diseases, especially viral hepatitis. Also talked about alcohol use with the patient, something we didn't really address in the previous case. But anytime we suspect steatosis, alcohol use has to be a question as well. I think a good first line exclusion of chronic liver disease is a really nice addition by the time they get to hepatology for those who do get to us, because then we can just take over. This is, we're going to go to MASH pathway, we're going to talk about treatments, clinical trials, prognosis and longitudinal monitoring and so on. If it's not done, we do it in hepatology. But it's always very nicely welcomed by us to have that done. The other things that could be done in primary care would be an olastography and that would be the next step. Just like we talked in the previous case, if fibroscan is available, or MRE or elf, whatever is available in that health system as a first measure would be nice to perform. Why is that? Because not everybody who may have MASH with abnormal liver enzymes and a high fib four really needs to get to hepatology. Let's say this patient may have stage one or mild fibrosis. We don't necessarily do something different than it would be done in primary care. I would say for us we would like to see stage two or higher. So moderate to advanced disease. So it's still helpful for those who do have these tools in their toolbox in their health system to be done before they get to us. If they're not available. Yes, please send them to hepatology because then we will do the screening on our part. So to answer your question, if they get to us with exclusion of chronic liver disease and with some method of. Non invasive method, not a biopsy, a non invasive method of estimation of fibrosis. We, we are very happy.

[A]

That sounds great. That's so helpful. So we've gone over diagnosis in some detail. Alina, can you go over what's available? And I know we did a deep dive last time. But briefly, what's available for treatment. So that patient who, our first case, who eventually had transient elastography in the nines. What's available and what's in the pipeline? Cause this is gonna be become just more and more relevant as time goes on.

[B]

Yes, it is a very exciting time for hepatology, especially for those who treat MASH and for the patients who have this disease. We have two FDA approved medications for the MASH indication. Both are for the stage of fibrosis that is moderate to advanced. The first medication was approved in 2024. It's called Resmetirom or Residifra and it's a thyroid hormone mimetic that is a liver directed agent. So it's not going to affect systemically the thyroid levels, but it revs up the metabolism in the liver to decrease steatosis, inflammation and even fibrosis. The second FDA approved medication was Semaglutide or Wegovy, which primary care physicians are more than hepatologists familiar with. This drug also approved for weight loss. So this is another indication that is for match with stage two or three fibrosis. This was approved in August of 2025. So fairly new indication for this. Which medication to prescribe or to choose in hepatology. We discuss with the patient, we talk about the risks and benefits or side effects. Side effects are probably about similar and they relate to GI. Just like with the GLP1s. The effects are also sort of, the effectiveness is also similar. The difference is that resmetirom is weight neutral. So we will not get a weight loss. In addition to the liver beneficial effects, it does have a decrease in LDL cholesterol which is also beneficial. In these patients who have metabolic dysfunction, a lot of them have dyslipidemia. But the other benefits of semaglutide on the other side of the coin are many. Based on the literature in the diabetes world and in the weight loss weight management world. So there could be improvement in, in glycemic control, in secondary prevention of cardiovascular risk and all the other things that come with the GLP1. So we discuss with the patient, we talk about all these things, we look at all the other risk factors that they may benefit from one medication or the other to make the choice. In primary care. I think you have semaglutide as a pretty easy to use medication. So if they have an indication for weight loss, for example, or for, you know, you can, you can either use that and you know that you'll, it'll treat liver disease as well or maybe if their insurance did not cover the weight management indication, you could try for the liver indication. So that's one additional benefit there. There are several in the pipeline. A lot of them are GLP1 based. The other two that you are familiar with will be retatutride and tirzepatide, both studied in a phase three trial. Currently they have been studied in phase two trials either as a MESH independent study or a sub obesity subgroup of obesity trials. Both have very promising improvements in steatosis, inflammation and fibrosis. So we are eagerly waiting for the results of the phase three trials to hopefully have those approved as well for liver disease if they prove their safety and effectiveness. Effectiveness as they did in phase two. And then servolutide is another dual agonist of GLP and glucagon receptor, which is also studied in a phase 3 trial now based on very encouraging and promising phase 2 data in fibrosis improvement in addition to MASH resolution. So it's a very exciting field because we have two drugs and we have several. I just mentioned these three, but there are FGF21 agents also in phase three trials. So we will have a lot of tools in our clinics in hepatology in the next few years, which is very exciting. Including the population that currently does not have a lot of options, which is those with cirrhosis. So those are also in the pipeline.

[A]

Come back to the cirrhosis issue and thanks for going over the treatment in that detail. Let's say we're seeing someone, as we did in this first case, and we've decided that transineal osteography fits advanced fibrosis. We're used to using a GLP1. We decide to use semaglutide, which is now FDA approved. And you had mentioned being careful to rule out cirrhosis. Can you be clear on why we need to be careful about that and how to look at that? Look for that?

[B]

Yes. Very common clinical question and very pertinent. So I'm glad you brought this up. Caution I advised on earlier is based on the fact that they have not been yet studied in a phase three trial for cirrhosis. So the FDA approval is not given in this indication. The large trial was in stage two to three fibrosis where we know it's safe and effective. It's not to say that they should not be or they're contraindicated in cirrhosis. They just don't have an indication for mass cirrhosis. If the patient patient happens to have cirrhosis and they have an indication that will be a glp, one appropriate one, such as diabetes or excess weight. They can be used in that population however they need. I think they need to be counseled for the risk of sarcopenia, which is more important in this patient population than the general population. Because patients with sarcophagus cirrhosis, most of them, if not all of them, have sarcopenia. Cirrhosis is a highly catabolic state and we don't want to make that worse because it has been proven many times that sarcopenia and frailty are associated with poor outcomes in patients who live with cirrhosis. So in that population there should be caution monitoring that they don't lose weight too fast or too much. They need to be counseled to supplement supplement protein in their diet at a reasonable amount of 1.6 grams per kilogram of ideal body weight. And they do need to be counseled to start resistance type of exercises to maintain that muscle mass. So that's the caution I would make there that's helpful.

[A]

And what are we looking for to know that someone has cirrhosis? Is that apparent on their ultrasound or is there any different tests that we.

[B]

Need to also order pieces of the puzzle? As I said before, I think there are. You know, first of all, elastography is a very good tool to, to assess that because it is the closest estimate for fibrosis estimation. For fibrosis level. Each of the elastography techniques have cutoffs for estimation of cirrhosis range. So in fibroscan a VCT of you 12 or 15 or higher, this is cirrhosis. In Mr. Elastography 4.6 or 5 or higher, it's cirrhosis. For an elf, 11.3 or higher is most likely to be cirrhosis. In those patients who have these high values of non invasive tests, I would do a cross sectional imaging or an ultrasound. So either CT or ultrasound to look at the morphology of the liver. None of the elastography measures give you the morphology of the liver. So we would be clear curious. Does the liver look nodular? Does the spleen look enlarged? Are there signs of portal hypertension? Is that platelet count around 150 or lower than that fib 4 then would be high in that situation. So it's a constellation of findings. But imaging is crucial in that situation because it's hard to diagnose cirrhosis otherwise so helpful.

[A]

This is a rapidly changing area. We're seeing advances all the time. And speaking of time, we're about out of time on this podcast. Alina do you have any final thoughts for our listeners?

[B]

I want to applaud the interest in this disease. I would like to meet again, maybe in a handful of years or less, where we say that liver is, is part of that check. And as, as, as much of a burden as we know exists in the clinic for all the checks you have to do, for which I have a lot of sympathy, I think liver will need to deserve its own space. Just like the eyes and the kidneys and the nerves, all those are checked in patients with diabetes. So that's my hope. I would like to end on a hopeful note and I hope that we will celebrate this achievement in the next few years. Is liver is a quality measure in patients who have diabetes?

[A]

Sounds great. Dr. Alina Allen, thank you so much for joining us.

[B]

Thank you very much for inviting me again.

[A]

Neal and sue, your final thoughts?

[C]

Yeah, you know, I think today's discussion really hit home the importance of finding this in that moderate to severe stage before it gets any further right. And there's so many things we can offer patients. So I think it really is a push for us to start screening. And I try and identify this as early as possible. And I feel like from a primary care perspective, it's a reason to double down on all of the lifestyle interventions we're so good at to help our patients who have metabolic risk. We want to prevent this as much as we can. And so I think it's just another reminder that, you know, that that really is a superpower we have to give to patients. But, gosh, I learned so much. I love doing these clinical cases.

[A]

And Sue, I always learn from you when we discuss things. Dr. Sue Couture, thank you so much for joining us. Joining us.

[C]

My pleasure.

[A]

And most of all, of course, thanks to our listeners. Thank you for joining us on this third of the three part series on mash. In the first episode, we talked about the epidemiology of mash, how it progresses, the consequences, and a deep dive on screening. In the second episode, we talked about diagnosis and really discussed treatment in detail. And here in our third episode, we looked at different perspectives and talked about clinical decision making and hopefully consolidated some of the knowledge that we discussed in our first two episodes. This special series of Diabetes Core Update is sponsored by Behringer Ingelheim. We thank you for listening. For the American diabetes association, I'm Dr. Neal Skolnick. Till next time, stay safe, keep learning. Sam.