Treating MASLD and MASH
Our expert roundtable on MASLD and MASH takes a dive into the treatments now approved for MASLD and MASH and how to approach shared decision-making with patients when choosing therapeutics.
Robert Fontana, MD, is a professor of medicine and director of the Transplant Hepatology Fellowship Program at University of Michigan Medicine in Ann Arbor, Michigan. Manal Abdelmalek, MD, FAASLD, is a professor of medicine and director of the Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) Clinical Research Program at Mayo Clinic in Rochester, Minnesota. Juan Pablo Arab, MD, is associate professor of medicine and the inaugural director of Alcohol Sciences at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University (VCU) Health in Richmond, Virginia.
Clinical Practice Summary
MASH Treatment: Patient Selection, Therapy Choice, and Multidisciplinary Care
- Resmetirom and semaglutide target noncirrhotic MASH with F2–F3 fibrosis. Noninvasive guidance thresholds vary: VCTE 8–20 or 10–20 kPa. Higher values warrant assessment for cirrhosis using platelets and imaging; neither drug is approved for cirrhosis.
- Treatment discussions should consider daily oral resmetirom versus weekly injectable semaglutide, weight and glycemic benefits, patient preferences, and insurance access. One academic clinician reported resmetirom reauthorization challenges beyond 2 years.
- Hepatologists manage liver-directed therapy and assess liver response while partnering with primary care or endocrinology for diabetes and lipid management.
Transcript
Dr Fontana:
So let's maybe pivot now towards treatment of MASLD. So we've done blood-based biomarkers, we've done imaging. Most of us will use VCTE. So JP, what are the parameters for... We have 2 FDA-approved treatments, resmetirom and semaglutide. What are the parameters for them to be considered for treatment these days?
Dr Arab:
So basically both of the studies we're trying to identify the same population. So it's a population with fibrotic match or at-risk match that is also called. So it's when you have a steatohepatitis, so inflammation, and you have fibrosis within the F2, F3 range. Since we are not doing liver biopsies in practice as often, we can use noninvasive tests. And then there is 2 different guidances. One is the AASLD and then the kind of consensus guidance. And one goes between 10 kilopascals and 20, and the other goes between 8 kilopascals and 20. But basically that is going to give you the range where you can consider treating this patient with noninvasive tests if you don't have a biopsy saying F2, F3. We need to be careful—none of these drugs has been approved for cirrhosis. And depending on what is the higher cutoff that you are going to use, you may be including some patients with cirrhosis.
So 15, you are on the safer side, but it's a narrow range if you're using between 10 and 15. If you use 20, it's fine, but probably we need to incorporate other elements for making a decision—for example, platelets or any other evidence. If you have evidence in the imaging that there is portal hypertension, well, be careful oin prescribing drugs in those patients because the trials were not done on that population. This may change, and I think now same companies are trying to test these drugs in more advanced population, but as of 2026 is with the F2, F3 MASH.
Dr Fontana:
Yeah. So I think that's a good point that it's noncirrhotic as we call it, an F2 to F3 by one of your NITs. But I have to say, I've been following this very carefully, the data looks pretty good in compensated cirrhosis with resmetirom and/or semaglutide, where there's I think a bit more data that it may be safe. We don't know about efficacy though. So I think we all need to pay attention to that. So be thoughtful currently, but maybe we'll get readout on those trials. My understanding is there's a 5-year study in compensated MASH that we should hear about within the next year or two with at least resmetirom.
So Manal, we both practice in the Midwest and for better or for worse, we have a lot of patients. How do you find getting insurance approval? We've talked about resmetirom, which is thyroid hormone beta agonist. We've talked about semaglutide, which is incretin. Do you find that insurance companies are telling you pick this, don't pick that? Are patients saying, no, I'll only take this, I'll take that. How do you propose therapy and what actually happens in your practice?
Dr Abdelmalek:
Yeah, so I'm at a big academic medical center, so I propose therapies, both resmetirom, semaglutide, and even introduce the opportunity for enrollment into clinical trials. When I consider resmetirom as a once-day oral pill, I have not actually had any difficulty with obtaining insurance approval, initial insurance approval, if I can justify that a patient is indeed has MASH fibrosis stage 2 and 3 without cirrhosis. And I'm prescribing it of course for a liver indication. I have had success with keeping patients on resmetirom for maybe 1, possibly 2 years, but I'm not having as much success with reauthorization beyond 2 years at this juncture. So I was an early prescriber, so we'll have to see whether insurance companies are going to allow us long-term therapy. As hepatologists, we know that when we discontinue any treatment for chronic liver disease, the disease comes back. So I don't anticipate that therapies with either resmetirom or semaglutide will be short-term. We're going to need long-term anti-metabolic therapies.
For those patients who are very keen on the other benefits of a GLP-1, diabetes lowering, significant weight loss, and life-limiting kind of complications of obesity, semaglutide may in fact be a first-line agent with the addition of resmetirom down the road based on fibrosis and interest in liver targeting. But I do have that discussion. Some patients don't want weekly injections, others will embrace it. I've actually had more challenges getting approval for the GLP-1 for the indication of MASH than I have with resmetirom. So I seek other complimentary indications when seeking GLP-1, and that typically is diabetes, sometimes is obesity, but it really depends on the insurer.
Dr Fontana:
So as a gastroenterologist, if it's the patient's preference to try to lose some weight or try to avoid prediabetes going to diabetes and you prescribe semaglutide, let's say you can get it approved, do you then take on the management of the diabetes of the prediabetes? Who does what here? I think this is something that a lot of GI docs aren't really totally comfortable with or not sure what their role is. Do you have any advice for that?
Dr Abdelmalek:
I don't take on the management of their diabetes. I do assess diabetes as a variable when seeing them every 6 months to a year for their MASLD-related care because it is a modifiable factor. So I do monitor thyroid function, I do monitor lipids, I do monitor glycemic control. I don't assume primary provider role for those cofactors of disease. I will assume the primary provider role for liver-related and liver-targeted pharmacotherapies with resmetirom currently, and I comanage those patients who are on GLP-1 with assessment of their liver-related outcomes and response from a liver standpoint. That is how I approach my management. I just think it would be too cumbersome for any one physician to do this without partnerships and a multidisciplinary team.
Dr Fontana:
JP, what's your thoughts on that? I think this is a key point and maybe why some people are hesitating to get going on treatment. What's your thoughts on that?
Dr Arab:
Yeah, no, exactly the same as Manal. I try to partner. I mean, when we are in the multidisciplinary clinic, we have more support, but even patients that are coming to the general hepatology clinic, sometime they come and they already have the diagnosis of diabetes and endocrinology is following them. But honestly, most of the patients just keep a close discussion with the primary care provider. Usually they are very good at managing diabetes or hyperlipidemia. I don't take ownership of diabetes, for example, but I suggest to the PCP from a liver perspective, he will benefit from this, this, or that, and I suggest you to increase these or reduce this. But I think having a good partner in the primary care side or endocrinology if appropriate is very important for these patients.
Dr Abdelmalek:
Yeah. The uptake of GLP-1s has increased so significantly in the past several years that as JP experienced, many patients come to me already on a GLP-1 for any one of their other comorbidities for which they're using. And I'm really predominantly making the decision of combination therapy with resmetirom and if that's appropriate.
