Expert Roundtable on MASLD/MASH: Part 1

In part 1 of this multipart series on MASLD and MASH, Drs Nezam Afdhal, Meena Bansal, and Zobair Younossi provide an overview of the growing prevalence of metabolic-associated steatotic liver disease (MASLD) and metabolic-associated steatohepatitis (MASH) and how it tracks the increases in obesity and type 2 diabetes.

Nezam Afdhal, MD, is Chief of Gastroenterology and Hepatology at Beth Israel Deaconess Medical Center and a professor of medicine at Harvard Medical School in Boston, Massachusetts. Meena Bansal, MD, is Chief of the division of Liver Diseases and Director of the MASH Center of Excellence at Mt Sinai Medical Center in New York, New York. Zobair Younossi, MD, is chairman and professor of the Liver and Obesity Research Program at INOVA Health in Fairfax, Virginia, and chairman of the Global NASH Council.

CLINICAL PRACTICE SUMMARY:

• MASLD (metabolic dysfunction–associated steatotic liver disease) and MASH (metabolic dysfunction–associated steatohepatitis) are rising in the US and globally, paralleling obesity and type 2 diabetes. MASLD is the most common liver disease worldwide with an estimated global prevalence of ~38%, with higher prevalence in Latin America, the Middle East, and North Africa, and substantial disease burden in Asia. MASH, the progressive liver disease subtype, affects ~5–7% of the general population; among patients with type 2 diabetes, ~70% have MASLD, ~60% have MASH, and ~20–30% have significant fibrosis.

• Clinical impact includes earlier and more severe liver disease across care settings. US hepatology practices report increasing numbers of younger patients with advanced fibrosis and cirrhosis, driven by childhood obesity and earlier onset of type 2 diabetes. MASH-related liver disease is an increasingly common indication for liver transplantation and is becoming a leading cause of hepatocellular carcinoma as hepatitis C declines.

• Screening and triage are expanding due to increased awareness and FDA-approved therapies. Multisociety-aligned algorithms emphasize noninvasive testing: initial risk stratification with FIB-4 (<1.3 to rule out low risk), followed by secondary assessment (e.g., VCTE/FibroScan). In practice, VCTE-only visits are used to manage volume; liver stiffness >8 kPa prompts hepatology referral, improving linkage to care for advanced fibrosis.

TRANSCRIPT:

Hello, everyone, and welcome to this Expert Roundtable on MASLD-MASH. I'm joined with a very distinguished faculty. My name is Nid Afdhal. I'm the Chief of Gastroenterology and Hepatology at Beth Israel Deaconess Medical Center and a professor of medicine at Harvard Medical School. I'd like to introduce Dr. Meena Bansal to you.

Dr Bansal:

Hi, I'm Meena Bansal. I'm a hepatologist at Mount Sinai in New York and chief of the division of Liver Diseases and Director of the MASH Center of Excellence.

Great to be here.

Dr Younossi:

Yeah, I'm Zobair Younossi. I'm a hepatologist in Washington, DC. I'm the chairman and professor of the Liver and Obesity Research Program at INOVA and chairman of the Global NASH Council, and I'm delighted to join this panel. Thank you.

Dr Afdhal:

Great. Let's get started and maybe discuss a little bit about what's happening with MASH and MASLD here in the US, but also use Dr. Younossi's expertise to discuss some of the global trends that are taking place as well. So I know, Meena, that you see a lot of patients with MASLD. Tell us a little bit about how you see the prevalence of the disease now in the US and what you feel are the major factors contributing to its continued growth.

Dr Bansal:

Sure. Yeah, no, we're definitely seeing increasing rates of MASLD and MASH with significant fibrosis. And I think Dr. Younossi has done a lot of the work really characterizing the rising epidemics of this disease globally, largely kind of going in parallel with the rising epidemics of type two diabetes and obesity. And I think with those going up, we're also seeing MASLD and MASH go up. I think one of the biggest advances is that we're now starting to screen more vigorously because there's increased awareness of the disease, which I think has come, and I'm sure we'll talk a little bit more about it, but I think now having FDA-approved therapies has increased the screening and the detection of those with advanced fibrosis and linkage to care.

Dr Afdhal:

Excellent. It's interesting when you say it's paralleling the rise in obesity and type two diabetes that we're seeing in the US, but some of the more recent data, which is very interesting with the introduction of the GLP-1 therapies for obesity has suggested actually there's for the first time in multiple decades, there's a little bit of a decline. So Zobair, why don't you give us your viewpoint on what's happening with MASLD and MASH?

Dr Younossi:

So MASLD is sort of the umbrella term. It's a part of what we call steatotic liver diseases now that includes Met-ALD, a group that will have both metabolic fat steatotic liver disease as well as some moderate amount of alcohol, and then of course alcohol-associated liver disease. That's sort of the largest spectrum. It's important to remember that MASLD as the umbrella term that includes MASH is the most common liver disease with the global prevalence of about 38%. There are certain regions of the world that have higher prevalence— Latin America, Middle East, and North Africa have very high prevalence rate, but there are other regions of the world that, although the prevalence is not as high, at42%; then for example, Asia, the prevalence somewhere between 25 to 27 or 30%—that the number that they contribute to the burden of disease or their disability adjusted live years lost from Asia, especially from China, is just immense and they're going up.

The reason I mentioned that there is a difference between the MASLD itself and then really what the disease is. So the disease, the liver disease is MASH. That's the progressive type of MASLD. That prevalence in general population is somewhere around 5 to 7%. Again, parallels those of type 2 diabetes and obesity, especially in the context of type 2 diabetes. Not only the prevalence of MASH is higher in patients with type 2 diabetes, about 70% of patients with type 2 diabetes will have MASLD. Almost most of those patients, 60% or so, will have MASH, and about 30%, somewhere between 20 or 30%, of them will have significant amount of scarring of the liver, or fibrosis. So the fact that the visceral obesity and type 2 diabetes is driving this really is driving the liver disease related to the steatotic liver disease, which is really the MASH subtype of MASLD.

Dr Afdhal:

Fantastic. Obviously, we are all gastroenterologists and hepatologists, and for us, the impact is really what we're seeing in our daily clinical practices. We're certainly here at the fatty liver disease clinic at BIDMC, we are seeing a significant increase in the numbers of patients with cirrhosis. And again, also in the age range and spectrum of those patients, we're seeing younger patients with more advanced fibrosis and even cirrhosis, because childhood obesity is also going up as is the earlier onset of type 2 diabetes. And of course, this is a major component of what we're beginning to see in our transplant populations, where we're beginning to see an increase in the rise of MASH-induced liver disease as a cause for transplantation. And then finally in liver cancer, where here in our liver cancer clinics, MASH-induced liver cancer is also becoming the most frequent cause of liver cancer we're seeing.

And what we're really seeing now is the rise in MASH-induced liver diseases becoming clinically more apparent as obviously we've seen a decline in some of the other disease states, such as hepatitis C with the onset of the new DAAs. I wonder if your experience has been the same, Meena, and how you've been dealing with this increased incidence of significant liver disease.

Dr Bansal:

Yeah, we do a lot with our primary care and endocrine colleagues to do a lot of the screening algorithms. We can talk about how all the stars have aligned and all the societies have really suggested a very similar sequential algorithm for screening out the low risk patients using a FIB-4 less than 1.3, and then those greater than 1.3 needing something else. So the way we've been managing some of this increased volume is we do FibroScan-only appointments or VCTE-only appointments as well, so that allows for that kind of secondary triaging so that we don't overflow the hepatology clinics with patients who don't have significant fibrosis. So on a daily basis, we probably have at least 10 to 15 patients coming in just for VCTE. And if they have a KPA greater than 8, then that triggers the whole hepatology referral immediately. But like you, we're seeing an increased number of those with significant fibrosis and cirrhosis.

And unfortunately for many years, patients have been told, "Oh, you just have a little fatty liver disease." So they've known about it for 20 years, 30 years, but people minimized it really. It's just fatty liver disease. Don't worry about it, exercise, lose weight. And now they're coming to us with that more advanced disease. And I think this is where the nomenclature helped actually in that it put an emphasis on how serious this disease is and that it's not just a little fatty liver disease and that we need to take it seriously and screen for a significant fibrosis. And we can talk a little bit more about all those algorithms and NITs that have come into play.