Key Updates on the Treatment and Management of MASH
In this video, James Matera, DO moderates a roundtable discussion with Colin Browm, MD, Kunal Gupta MD, and Lisa Jones, MA, RD on recent developments regarding the treatment and management of metabolic dysfunction-associated steatohepatitis (MASH), the nutritional risk factors associated with MASH, the challenges and gaps that clinicians continue to see at their clinics, and more. This is part one of a two-part series on MASH.
Watch part two of this roundtable discussion here:
Additional Resources:
Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000
TRANSCRIPTION:
James Matera, DO: Okay. Good afternoon, and thank you for joining us for our roundtable discussion today on MASH and MAFLD. And I'm very honored to have with me three fine clinicians who are going to help guide the discussion. Dr. Kanal Gupta. Dr. Gupta is a board certified gastroenterologist with Middlesex Monmouth Gastroenterology, which is part of Allied Digestive, specializing in disorders of the GI tract and a focus on hepatobiliary disorders. Lisa Jones is a registered dietician and nutritionist and actually the section editor for Nutrition 411, The Podcast on Consultant 360. She's bringing her expertise in nutrition and a passion for wellness to the forefront of each episode and is going to provide us some wonderful insights. And finally, Dr. Colin Brown, who's also a gastroenterologist with the same group, Middlesex Monmouth Gastroenterology and focuses a lot on clinical research in his practice. So thank you all for joining me today.
I think this is a wonderful topic that we're going to look at. So if you look back to around 2020, we used different terminology. We used NASH and NAFLD and then we realized how metabolic this disease process is. So now we go by more of metabolic-associated dysfunction or metabolic dysfunction associated fatty liver disease or metabolic dysfunction-associated steatohepatitis. And I just think, in my opinion, this is kind of a continuum of diseases that we need to look at and certainly a cardiovascular risk factor. So let me throw a couple of questions out. I'm going to start with Dr. Gupta and Dr. Brown. Can you provide an overview of any recent developments that we've been seeing in the mesh and MASH and MALFD lineup?
Colin Brown, MD: So that's a great question, Jim. As we've known for a while, MAFLD and MASH fatty liver disease has really been one of the most explosive areas of liver disease that we are seeing. It's becoming the top reason for liver transplants. It is basically surpassing all the viral hepatitis as well as alcohol-related liver disease for causing morbidity and mortality among patients who have liver disease. And it's basically, there's an ocean of patients that have that. And because of the epidemiology of this disease and how much it's grown, there's been a lot of focus in the clinical research arena as well as among collision nations and nutritionists to see how we can stem the tide of this disease.
Dr. Matera: That's a great point. Kunal, I've seen studies that indicate about 30% of patients can have this. Is that something you agree with, you think? It certainly seems to be overtaking many of the other diseases, as Collin said.
Kunal Gupta, MD: Yeah, I mean it's widely underdiagnosed, right? I think that's the problem with this disease is that we don't have a good way to diagnose it early. We don't know, which as you said, it's very common. So we're not really necessarily interested in treating everyone with NAFLD or MASLD or MASH. We're really interested in trying to find out which patients are going to progress to cirrhosis. So as hepatologists and gastroenterologists, that's kind of what our job is to try to figure that out. And it's very difficult. We don't have very good modalities to try to figure that out. We can talk later about elastography. That's something that's kind of exciting that we started doing in our practice, and it's like a less invasive liver biopsy. But like I said, I think with the obesity epidemic, this disease state is more prevalent. I think that's kind of why they changed the name also because it used to be a diagnosis of exclusion, which it kind of still is, but it really was a non-alcoholic. But in reality, like Colin said, it's much more prevalent. And I think as the years go on, it'll be more and more prevalent, and it just puts more focus on this disease that we need to get a better understanding of. And at least now we see some better treatments available.
Dr Matera: That's great. That's good to hear because we also know it's contribution to cardiovascular disease and it's a cardiovascular risk factor. But I'm going to turn our attention here to one of the big risk factors is of course, weight, obesity, hypertension. And we know that that's just a risk factor in many different ways. But certainly here and the old days of just saying you have a fatty liver and not necessarily worry about it, I think are gone when you see this continuing. So Lisa, can you comment a little bit on where weight loss and diet and dietary modifications come in when you're seeing patients on this spectrum?
Lisa Jones MA, RDN, LDN, FAND: Yes, definitely. I think it's a perfect opportunity to really unpack the power of diet in managing liver health and explore some key approaches. And the first one I want to talk about is Mediterranean diet, because I like to think of the Mediterranean diet really it's a real game-changer. It's like turning your car for better performance, this diet tuned your body's metabolic pathways. It's helping everything run smoother from lipid profiles to insulin levels. So really here recommending a Mediterranean diet isn't just good advice. It's a strategic move in managing MASH effectively. And then if we want to talk a little bit about processed foods, we know our liver doesn't like being overwhelmed, high fructose, processed foods and alcohol, they're like unwanted guests at a party causing trouble. But by cutting these out, we're essentially giving the liver a break and helping prevent further damage.
So really we want to encourage our patients to steer clear of these dietary pitfalls. It's a crucial step in stopping MASH from progressing. And then to your point with weight management, weight is such a touchy subject, but in terms of liver health, it's critical. So managing weight, considering bariatric options when needed, it can really lighten the liver's load. And it's much like easing. When we think of kids with heavy backpacks taking them off their shoulders, you're lightening the load. So focusing on weight management is a cornerstone of mass treatment. It's vital for lifting that burden off the liver. And then I also quickly want to touch on GLP-1s because they're really multitaskers, they're not just good for weight loss, they also tweak insulin sensitivity, and they dial down sugar production in the liver. So it's kind of like having a thermostat that not only controls the temperature but also optimizes the energy use in your house. So I would say here, they're really good for MASH treatment because it harnesses these dual benefits, making them a powerful tool in our medical toolkit.
Dr Matera: I think those are all excellent points. And again, I'm so excited with the GLP-1s and the SGLT-2s. When you look across the spectrum, their effects on kidney, liver now certainly heart, these are amazing drugs. So thank you for that. Let's open this up to everybody. Let's start. What are some of the challenges or gaps that you see in our treatment of this disease as it becomes more prominent? Any gaps that we can try to narrow?
Dr Brown: So I think there's two things that are potential gaps but also gaps that as clinicians we can cross. And the first one is the gap in trying to address the underlying metabolic issues. And as Lisa said, really putting the focus back on the diet, putting what you can put into your body I think is a really important thing that clinicians sometimes overlook. But it's critical that we address these things during our visits with patients who come for a fatty liver disease. And I think exactly what Lisa said with respect to the Mediterranean diet and limiting processed foods is a really big step, but as clinicians, that's a step that we have to take over and over again and we don't always do a great job of addressing. I think the other gap is dovetails to what Dr. Gupta said earlier that we're trying to discern who among the fatty liver patients are going to progress to end-stage liver disease because it's an ocean of fatty liver. I would say a significant but relatively small proportion of those patients are going to develop end-stage liver disease. And trying to identify them and get them on the right track is sometimes difficult but also very important.
Dr Matera: Yeah, I couldn't agree more on that. Lisa, what do you see as some gaps? I know patient adherence, certainly nobody likes to live up to diets sometimes, but what are some of the gaps that you see?
Lisa Jones: Yeah, I would definitely say the other one too would be managing comorbidities. If you think about the holistic management of these conditions that frequently accompany MASH, you think about dyslipidemia, obesity, excessive alcohol consumption, of course diabetes. But each of these conditions require specific dietary adjustments. So that can be difficult in itself. So managing lipids might mean increasing omega fatty acids while controlling diabetes may involve a low glycemic index diet. So really it becomes complex at times. So as that complexity increases, we aim to balance these diets to address all comorbidities effectively without compromising one for the other
Dr Matera: Excellent points.
Dr Gupta: Well, for me, I think we're in an exciting time, like you said, Jim, with these GLPs, we're not pediatrician. Me and Colin are not pediatric doctors. We are adult physicians and I think majority of our patient population is above the age of 45. And I think, I don't know, I'm still trying to learn about, I think we all are trying to figure out what diet means, what obesity is, what is this drive, why do patients have these BMIs? I think majority of us don't weigh ourselves every day, but somehow we are consistently relatively the same weight decade after decade after decade. So why do people who all of a sudden are all with these GLP-1 drugs all of a sudden are losing weight? Why do people that undergo sleeve gastrectomy all of a sudden lose weight? So there is something there in terms of hormone driven drive to eat, and I feel like we don't give justice to the patients when we say that, oh, you just need to go on a diet.
I think it's more subconscious than that. And I think that these GLP-1 drugs are showing us that there's more to it than just not eating right or eating wrong or going on this diet or not. I think it's hormone driven. I think we need to at least admit to ourselves as physicians that we can't just keep doing the same thing over and over again and expect a different result. I guess that's someone defined that as insanity, we have to try new measures like the bariatric surgery. And now with these GLP-1s, I think we have to drive that home. You have to do things different and use these new therapies that are available. And I, that's extremely exciting, especially with talking with this disease. And then the flip side again is what Colin was saying. As hepatologists and gastroenterology, we are worried about our patients with this disease progressing to chronic liver disease and cirrhosis. But looking at this disease, the number one cause of death in these patients is going to be cardiovascular death. And so with the diet modification and with these GLP losing the weight, it will tackle that cardiovascular perspective or aspect of it.
Dr Matera: Yeah, it's great to have those backups for drugs that actually are multitasking, if you will. So I think that's fantastic. We are going to do a separate section on pharmacological therapy after this one, but just to finalize this segment on the horizon, do you see any new findings that may be helpful to us?
Dr Brown: So there's a few different areas of study. I think the one as Kunal and Lisa have mentioned and obviously is a big subject of conversation with the GLP-1s, and they're almost ubiquitous and they're certainly on multiple different levels affecting our hormonal drive for satiety. I think there's also more targeted therapies that are being developed, specifically looking at wands that can reduce the steatohepatitis component of the liver disease as well as the laying down of the fibrosis. So as you may know, the progression goes from fat buildup in the liver to inflammation of the liver leading to fibrosis of the liver, which can lead to cirrhosis and stage liver disease. And there are some molecules that are being looked at that can interfere with the laying down of the tracks of the fibrosis. And I think those targeted therapies are certainly something that's exciting, especially for people who have more of a liver problem as opposed to just a metabolic problem.
Dr Matera: Great. Any other closing comments from Lisa or Kunal?
Lisa Jones: No. The other thing I've been seeing some articles and research about is AI and is specifically voice biomarkers, which I find interesting because they're looking at it with diabetes right now. But I think it would be interesting as it kind of advances into other disease states to kind of look at that to see how we can explore that. But that kind of goes beyond the new medication and nutritional therapies, but I think it helps with the variability in diet response and if they can kind of tie the two together, I think that's a promising thing for the future. It's AI for good,
Dr Matera: AI for good. That's a good point. I look at AI as both a threatening opportunity to us in the future. Any last words for this session?
Dr Gupta: Again, I think that what is fascinating is just to be able to not look at this one disease as a liver problem or a GI problem, but metabolic syndrome and looking at it as a whole and tie in understanding that none of these diseases operate in isolation and we really do need to treat the bodies as a whole and talk to our colleagues and kind of work together to make our patients feel better.
Dr Matera: Couldn't agree more. Well, I want to thank you all for this really, really good conversation. It's so interesting to speak to people who really get it and I'd like to thank the audience for joining us. Just to summarize, let's remember that this is a continuum of diseases and our main goal is preventing cirrhosis. Number two I think, is to make sure that we understand that MASH and muffled are becoming much more prevalent and the tie-in with the risk factors really is a charge or a call to us as clinicians to really start to do modification here in order to stem that tide. So once again, thank you and please join us in the second session where we'll talk a little bit more about pharmacological therapy. Thank you.