'MASH Screening Made Simple'

 

Today we’re going to talk about MASH. That is metabolic dysfunction-associated steatohepatitis, which has emerged as a critical topic for us in primary care. We need to feel confident in our ability to screen for and care for patients with MASH because it is very common, our ability to screen for it is defined, it has severe consequences, and there’s now a lot we can do for it.

What’s fascinating is if we see 20 average primary care adult patients in a day, there’s a good chance we’re going to see one or two people with MASH. And there’s a good chance we didn’t realize we were seeing them. Approximately 30% of adults and about twice that percentage of people with type 2 diabetes have metabolic dysfunction-associated steatotic liver disease (that is, MASLD). About 20%-30% of those people have MASH.

I’m going to discuss the just-published Clinical Care Pathway for Risk Stratification and Management of Patients With MASLD from the American Gastroenterological Association that I had the privilege of contributing to as a member of the committee that formulated the pathway. Now, let’s face it: This is an area that is often confusing to us in primary care. The aim of this guideline is to help us clearly identify the people with MASH who have moderate to high-grade fibrosis and who therefore qualify for treatment.

Let’s start off our discussion today by clarifying the difference between MASLD — what used to be called nonalcoholic fatty liver disease — and MASH. First, what’s MASLD? MASLD is defined as having liver steatosis that is not due to excessive alcohol intake. MASH is then a subtype of MASLD where, in addition to there being steatosis, there’s inflammation going on that leads to ballooning of the cells and something called Mallory’s hyaline on biopsy. This in turn leads to fibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The fibrosis goes in stages, beginning with stage F1, which is mild, then F2 and F3, moderate to severe fibrosis, and then F4, which is cirrhosis.

The next question we can ask is, why is this important? Well, it’s important for two reasons. The first is liver-related. In the United States, MASH has become the most common cause of end-stage liver disease in women, and the most common cause of liver transplant in women, and the second most common cause in men. The second reason is elevation of cardiovascular risk factors. Individuals with MASLD have elevated cardiovascular outcomes with a risk that is between 30% and actually 2.5-fold higher depending on the severity of fibrosis when compared with comparable populations without MASH.

So, the goal of screening is to identify people with moderate to advanced fibrosis — that is F2 and F3 — because that’s where the risk of progressing to advanced liver disease rises dramatically, along with an important increase in cardiovascular risk. Also, this is the level of fibrosis that’s used as the criteria for enrollment in the intervention trials.

So how do we screen for F2 and F3 MASH? The pathway suggests a four-step process:

1. Identify patients at risk. The groups at risk for MASLD-related fibrosis who should be screened are: (1) people with diabetes; (2) individuals who have overweight or obesity and one additional metabolic risk factor (usual risk factors include high triglycerides, low HDL, hypertension, high cholesterol, prediabetes); or (3) incidentally found steatosis on imaging or incidentally discovered elevation of LFTs, which leads us then to step 2.
2. Assess alcohol intake and check a CBC with platelets as well as LFTs. You’ll see why we need the platelets in a moment. If someone has significant alcohol intake, address it. If someone has elevation of LFTs, then you need to do a workup for that. Once that is out of the way, that leads us to step 3.
3. Calculate a FIB-4 score. The FIB-4 score takes into account age, platelet count, AST, and ALT. The calculator is included in many electronic records. In Epic, if you put in the dot phrase “.fib4,” it’ll be automatically calculated for you. Or you can look at an online calculator. I’ve left a link below. If the FIB-4 score is < 1.3 (important here, though: For people older than 65 years, we use a cutoff of < 2.0), then the individual is unlikely to have F2 or greater fibrosis, and the recommendation is to repeat the FIB-4 score in 1-2 years. If the FIB-4 score is ≥ 1.3 (and that is ≥ 2.0 in people older than 65 years), then go on to step 4. Given the high prevalence of F2 or greater fibrosis in people with type 2 diabetes, in that group we are able to go directly to step 4 if we want to. When might I do that? Well, perhaps if someone has diabetes and a very high BMI and severe metabolic abnormalities.
4. Step 4 involves testing with a more specific test for fibrosis. That would most often be a measure of liver stiffness using ultrasound-based imaging called vibration-controlled transient elastography — that’s VCTE. Most commonly, that is the FibroScan. The cutoff used here is 8 kPa. If VCTE is ≥ 8 kPa, the person is at high risk for having moderate to advanced fibrosis (that’s F2 or F3) and warrants treatment. Usually, that’s referral to a liver specialist. If the number is less than that, then the recommendation is to repeat the VCTE in 3 years. An alternative is now available to VCTE, and that is the ELF test. ELF here stands for enhanced liver fibrosis test, which looks at three biomarkers of fibrosis to provide a score that indicates the risk of F2 or F3 fibrosis. It is simple; it is just a blood test. If the ELF is < 9.2, then repeat it in 3 years. If it’s > 9.2, then that individual may be eligible for treatment. 

It’s important to know that treatment for F2 and F3 fibrosis is now available that can slow progression and sometimes even reverse the severity of fibrosis. The two treatments that are currently FDA approved are resmetirom and semaglutide. There are many other treatments as well that are in the pipeline and phase 3 trials, including tirzepatide, the dual GIP/GLP-1 receptor agonist; survodutide, which is a dual GLP-1/glucagon receptor agonist; and others with mechanisms that most of us are unfamiliar with and which I have trouble pronouncing.

The other thing important to remember is that moderate to advanced fibrosis identifies a group of people who are at elevated cardiovascular risk and for whom the usual approaches to cardiovascular risk reduction — things like addressing hypertension, hyperlipidemia, obesity, diabetes, chronic kidney disease, physical activity, and diet — are critically important.

So, this is an important practice pathway. To review briefly: Understand who to screen [and] check for alcohol use and other causes of LFT elevation. If the LFTs are elevated, calculate a FIB-4. If it’s > 1.3, or > 2.0 in people older than 65 years, check elastography or an ELF to determine who needs treatment.

Remember what I said at the beginning of this discussion? If we saw 20 adults in primary care today, it’s likely that one or two of them have MASH with elevated fibrosis, and we might not have known that. This pathway from the AGA gives us clear guidance on how to identify those people.

Neil Skolnik, MD

Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia; Associate Director, Department of Family Medicine, Abington Family Medicine, Jenkintown, Pennsylvania 

Disclosure: Neil Skolnik, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Teva; Lilly; Sanofi; Sanofi Pasteur; GSK; Bayer; Abbot; Novo Nordisk
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Lilly; GSK; Teva; Bayer; Heartland; Astellas
Received research grant from: AstraZeneca; GSK; Novo Nordisk; Novartis

https://www.medscape.com/viewarticle/mash-screening-made-simple-4-step-guide-2026a1000cz3