Screening for MASLD and MASH: Expert Roundtable Part 2

In Part 2 of this expert roundtable Drs Afdhal, Bansal, and Younossi discuss how to determine which patients need to be screened for MASLD/MASH, how to conduct screening, and which modalities are best.

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:

• Target population for case finding: MASLD/MASH is a leading cause of liver transplantation and liver cancer in the United States, and guidelines emphasize case finding rather than population screening. High-risk groups include adults with type 2 diabetes, patients with obesity plus other metabolic abnormalities (eg, hypertension or dyslipidemia), and anyone with abnormal liver enzymes. The goal is to identify high-risk MASLD (often MASH) associated with adverse outcomes, with most low-risk patients managed in primary care and a minority requiring further evaluation.

• First-line screening test and monitoring: US societies align on FIB-4 as the initial test in high-risk patients because of its strong negative predictive value. A FIB-4 <1.3 indicates low current risk and can be managed in primary care, with repeat testing annually or semiannually to capture progression. In a large US health system, ~87% of patients with diabetes already had available labs to calculate FIB-4 without additional testing, supporting feasibility and cost-effectiveness.

• Second-line assessment and referral: A FIB-4 ≥1.3 warrants further risk stratification using liver stiffness assessment with vibration-controlled transient elastography (VCTE) where available, or the enhanced liver fibrosis (ELF) test if elastography is not accessible. Patients with elevated second-line results should be referred to hepatology for advanced fibrosis assessment and management, while care pathways increasingly integrate automated FIB-4 calculation and prompts within electronic medical records.

TRANSCRIPT:

Dr Afdhal:

What we really do want to discuss next, which is how we approach the patients that potentially have the more significant form of MASLD, as Zobair said, who have MASH and who we screen, how we screen them, and what modalities we're using and what's available to us to use. And obviously there are different modalities available in different parts of the country. And in sophisticated units, there is the ability to do VCTE, and many of us have multiple machines and actually have open VCT clinics for our primary care doctors. But at the end of the day, I think I'd like just to start off with who do we recommend, from the primary care viewpoint, should we be screening? Which patients should we be screening? And then maybe focus a little bit on how we should be screening them, looking at first steps, second step referral patterns.

So Zobair, who should we be screening?

Dr Younossi:

Yeah, let me just make one comment before we get to the case finding issue. We are seeing at the tip of the iceberg because remember MASLD or MASH is the second indication for liver transplantation, both in Europe and United States. The number one, probably, reason for liver cancer in the United States, but it also actually impacts other liver diseases. So for example, if you happen to have viral hepatitis and you also have superimposed MASLD or MASH, then disease is probably more aggressive. So it probably contributes to burden of disease and the risk of the world directly and also indirectly. Now, in terms of whom should we screen, screening is usually for general populations. So just the terminology that in this case, we're doing case finding. What does that mean? That means that we are going outside the individuals who are really at highest risk.

And I would say that there are 3 or 4 sort of categories of patients—those who are diabetics when the reason is that the prevalence of both, it's really not NASH or MASH that we are trying to find. We're trying to find what's called high risk MASLD. So these are the patients that are at risk for adverse outcome. And most of those patients are MASH, but there are some others that will have high risk MASLD. These are the type 2 diabetics or what I would call complicated obesity. So someone who's obese and has one of the other metabolic abnormalities—hypertension, dyslipidemia, et cetera. And of course, anyone who has abnormal liver enzyme, that's just of course as a practice that we have to do. So this is the group that will be the target of initial case finding to find that needed in the haystack of the few patients that will have the high risk, potential for high risk outcomes. And you want to find it so that the risk of the patients, when you do the FIB4, the 80% that will be low risk with massive data, they can be managed by primary care, but 20% that could potentially be high risk after the first line testing can get second line testing and then of course manage in a different way.

So that's really what most of the guidance and the guidelines are focusing on.

Dr Afdhal:

So it's worth pointing out that the American Diabetes Association is actually ahead of us in many ways with this. And even before our own societies such as AASLD recommended screening of patients with diabetes for the presence of significant fibrosis and MASH, the ADA was very, very proactive in stating that we need to evaluate liver disease in diabetics in a more aggressive fashion and have very similar guidelines, as Meena pointed out to us. Meena, you were going to say something.

Dr Bansal:

No, I was just going to say, I think that focusing on the patients living with diabetes is actually probably the best first step because I think that when we try to push for, say, a quality measure in screening for end organ damage, in patients with diabetes, the endocrinologist and the primary care are used to looking at end organ damage in those patients. So there's already quality measures for screening for nephropathy, there's measures for screening for retinopathy. So I think focusing on the patients with diabetes because they have the highest risk for having significant fibrosis and the denominator is very clear. And so when we look at kind of numerator compliance and screening and we'd say, "Okay, what percent of our patients living with diabetes have we screened for advanced fibrosis?" It's very calculatable. And I think that getting the endocrinologist to drink the Kool-Aid, if you will, they're used to doing these things already.

So kind of adding on screening for diabetic hepatopathy or MASH with significant fibrosis just makes a lot of sense. And I think for us as an organization, pushing for a quality measure with CMS, with Battelle and these organizations is really what we need to do. And once people drink the Kool-Aid for screening in that population, which is very clear, then we push for the other high-risk populations like those with complicated obesity, et cetera.

Dr Afdhal:

So I'm a primary care physician, let's say, and I have a patient in front of me who has type 2 diabetes pretty well controlled just on metformin, and is mildly obese, BMI of 32. As a primary care physician, what's my first screening test that I need to be doing? And then what is the next step, assuming that's positive? So what would you recommend?

Dr Bansal:

So I think all the societies have aligned on doing a FIB-4 test as the first line of defense for just kind of ruling out, not a very good rule-in, but a good rule-out test with good negative predictive value. And so if the FIB-4 is less than 1.3, there's a low risk right now. The caveat being that we need to be repeating that test on an annual or semiannual basis because that just gives you one snapshot. And it's important to note that some people have rapid fibrosis progression, but some people will never progress. So longitudinal changes over time are very important. But that being said, so that first line of defense, because the labs are usually already there, so you don't have to spend money to do a test. When we looked at our patients living with diabetes at Mount Sinai, we have about 55,000 diabetics that are kind of attributed to us in our health system.

And we looked, 87% had the requisite values to calculate a FIB-4 with absolutely no education. So it's just doing the math. So I think from a cost-effective way, it's just a good first line. After that, then you need better rule-in tests. So once you have a FIB-4 greater than 1.3, you need something else. And most of the guidelines have recommended either a VCTE, a liver stiffness assessment, or if you don't have access to that, an ELF test, the enhanced liver fibrosis test, has been proposed as a second line to then see who needs to go on to see hepatology.

Dr Afdhal:

Yeah. And I think most places now are following those guidelines. And certainly in our healthcare system, we actually have the FIB-4 calculated in the medical record and it appears for the primary care physician because all you need is the ALTA is the age and platelet count and you can calculate a FIB-4 and then a screen will appear saying elevated FIB-4 greater than 1.3 and a suggestion to obtain either liver elastography or as you said, the ELF test, which is again, a kind of more specialized test for liver fibrosis and about an equal cost to performing a VCT if it's unavailable.