Monitoring Patients With MASLD/MASH

Our expert roundtable on MASLD/MASH reviews how to monitor patients on treatment for MASLD/MASH, including the use of PEth tests to detect alcohol consumption that may be reducing efficacy of medical therapies. 

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

Monitoring response to GLP-1 agonists and resmetirom 

• In patients with MASH treated with GLP-1 agents and resmetirom, efficacy assessment should focus on liver disease (not weight or glycemic control); although approvals were based on biopsy endpoints, current practice relies on noninvasive tests (NITs) such as VCTE, MRE, ELF, and MRI-PDFF, with early trends (≈6 months) used for directionality and formal efficacy assessment at ~12 months.
• Suggested NIT response thresholds correlating with histologic improvement include ≥30% reduction in VCTE, ≥20% reduction in MRE, and ≥0.5 decrease in ELF score; ≥30% MRI-PDFF reduction (early) is a strong predictor. Clinicians should also track ALT normalization and CAP score reduction (especially with GLP-1–associated weight loss). Even without meeting thresholds, continued improvement in directionality supports ongoing therapy, reflecting the time-dependent reversibility of liver injury.
• At 1 year, treatment discontinuation should be considered if worsening occurs (e.g., ≥20–30% increase in VCTE), after excluding confounders such as alcohol use, which should be routinely assessed using AUDIT-C or PEth testing. Preventive care includes hepatitis A/B vaccination, and advanced disease monitoring (e.g., liver stiffness ≥25 kPa signaling portal hypertension risk). Ongoing real-world data will clarify clinical outcomes beyond biopsy-based surrogate endpoints.

TRANSCRIPT:

Dr Afdhal:

So our patient now is on a GLP-1, on resmetirom, we're going to follow our patient. When new drugs come out, and obviously what you're trying to do is you're trying to determine, is my patient having a good efficacy from these drugs for his liver disease? I'm not saying, are we well controlling his diabetes or is he losing weight? Those we hope are happening. But the studies upon which the approval of these agents were based were biopsy-based studies. And we've all agreed that we don't do biopsies anymore. So as a practitioner, what you want to know is you want to know what should I be doing to look to see is the treatment working? How do I monitor my patient? What frequency of monitoring do I use and what tests and what types of results am I looking for? And I know that there's, again, not great guidelines on this, but there is data out there that helps us with that data on changes in percentile changes in liver stiffness, et cetera.

So I want to get a more practical thing. Meena, I want you to tell me, what do you do at Sinai when you're following these patients

Dr Bansal:

Now? Right, right. So I generally don't do any kind of look until about 6 months onto the treatment. Generally speaking, you'll see a reduction in liver enzyme. So kind of like what did you use to justify starting the treatment? So what NIT did you use? Did you use VCTE? Did you use ELF? Did you use MRE? Whatever that might be. You obviously want to look at a delta in that. So I don't look at efficacy at 6 months. I just look at kind of are things moving in the right direction, but really I don't look at efficacy till a year in. And as you point out, there are percentages. So a greater than 30% reduction in VCTE, a greater than 20% reduction in MRE, or an ELF score reduction of 0.5 have all been kind of suggested to correlate with histologic response. If by chance you use MRI-PDFF, but I don't think that's happening in the practical real world. And if you see this 30% reduction early on in MRI-PDFF, that's the best predictor for histologic response.

So I think that those are the slam dunks. So I kind of say these are the slam dunks. If you hit that threshold of greater than 30% VCT, this is definitely working and not just by chance because of the coefficient of variability of VCTE. But the reality is, is if everything's moving in the right direction, even if you don't quite hit those thresholds, you're not going to stop. You're going to just kind of say, okay, maybe fibrosis takes time to progress and it takes time to regress. So as long as all my NITs are moving in the right direction, I just keep marching on.

Dr Afdhal:

That's a fantastic summary because I think that directionality and the concept of time are absolutely critical because in every other liver disease that we deal with, whether it be eradicating hepatitis C, whether it be suppressing hepatitis B, the reversibility of the injury takes time. And if you suppress HPV for 5 years, you can reverse cirrhosis. So we know the importance of time as a factor for resolution of the liver-related injury. So very nice.

And again, I throw in at the early time point when I evaluate these patients, I throw in reduction in CAP score, especially if they're on a GLP-1, if I'm using elastography, because you will see, if they've lost any weight on the GLP-1, a pretty good reduction in the CAP score. And I also, in those with elevated ALT, I love to see ALT normalization. It's just one factor that makes me very happy that the necroinflammatory component may be improving in these particular patients.

Zobair, do you do anything else that's different, let's say you've got your patient, are there other things that you address, other comorbidities? Vaccinations which are very topical today? Are we vaccinating all our MASH patients for hepatitis A and hepatitis B? What else should we be looking at now in this year our patient is on treatment?

Dr Younossi:

I think that's what we follow. I think vaccination is recommended in our guideline and for all patients with liver disease, we're going to have to do the vaccination and we're going to continue to recommend that.

I think the one thing that in addition to monitoring and giving treatment that I actually brought into my practice is to measure for alcohol consumption during treatment because that can actually reverse things without your knowledge because alcohol consumption is underreported by history significantly. And you can do it in two different ways. You can do a questionnaire which is AUDIT-C, which is only three questions or you can now do a blood test called PEth testing. And PEth can tell you if the patient is actively drinking.

Why is that important? Well, it's important because even if you're not responding or you're worsening and you're trying to make a decision after a year, so you're treating a patient for one year and the numbers are actually going in the wrong direction, you're supposed to stop. Because that's the only time that if you confirm worsening of by 20% or 30% of VCTE, then you're obligated to say, "This is not working."

Now, what you want to make sure is that there's something else that's not going on there that's actually worsening things and that's alcohol. So I would recommend that getting into the habit of doing routine testing for alcohol just because it's so common and it's so under-reported in this context. Then of course, all the other preventative hepatology stuff that we do is important to monitor. Now we know, for example, that if you have a patient that is developing cirrhosis, once you get to a stiffness of 25 or higher, you have to worry about portal hypertension and you may not need actually a endoscopy or things like that. So those are the kind of things that we do.

Dr Afdhal:

So I have to say that the comment on PEth testing is a very, very good one. And when we teach our fellows, we say, "Did you order a PEth test?" And the fellow's like, "Well, he doesn't drink. He told me he didn't." I said, "Just get the PEth test." Again, I think many of us are using it routinely now as one of our liver function tests, if you want to call it that, just to continue to monitor our patients.

All right. So we're only in the infancy of the treatment paradigm for MASH. It's very exciting to have new treatments, but we're really one year, some patients, maybe 18 months, on resmetirom. Real world data is beginning to emerge. Many of us are involved in developing those datasets, utilizing good registries, but also utilizing big data with AI algorithms to look at outcomes in these patients across broad swaths of the community. Because again, what we're talking about is 3 specialized centers of liver disease. And I'm always very interested in what's happening in terms of what's happening in the community base and the general gastroenterology base as well. So I think we'll see a lot of real world data that will inform us a little bit more about monitoring and maybe even some stuff on efficacy.

And it's also important that the audience is aware that these drugs are all approved as part of an FDA process called subpart H, which essentially means that you have approved a treatment because the early data suggests the treatment is efficacious, which was based on the liver biopsy findings that Meena pointed out, improvement in cirrhosis without worsening of NASH or improvement in NASH without worsening of fibrosis. And what is ongoing and possibly very critical to understand is whether these changes are going to result in improved clinical outcomes.