Diet and Alternative Therapies in MASLD and MASH
Drs Fontana, Arab, and Abdelmalek continue their discussion on the treatment of MASLD and MASH, discussing the importance of dietary therapy and the possible addition of vitamin E for some patients, as well as getting follow-up imaging to assess patient progress.
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 Management: Dietitian Support, Alcohol Assessment, and Treatment Monitoring
- MASLD/MASH: Dietitian support, Mediterranean-style eating, 7%–10% weight loss, and resistance plus aerobic exercise underpin care regardless of fibrosis stage or medication use. Serial dietary sessions support ongoing management.
- Alcohol monitoring: Panelists use PEth testing and counsel alcohol avoidance during treatment because alcohol can confound steatosis measurements and treatment-response assessment.
- Resmetirom/semaglutide: Use the same imaging platform as baseline. Dr Abdelmalek assesses resmetirom with VCTE at 6 and 12 months and semaglutide at 72–92 weeks. Dr Arab does not stop treatment solely for absence of improvement at 6 months.
Transcript
Dr Fontana:
Our audience here is largely practicing luminal GI docs, if you will. And I think we are all trained in the importance of diet these days, managing EoE, managing irritable bowel syndrome, managing inflammatory bowel disease. So I think a lot of practicing gastroenterologists have good relationships with a dietician to help them with their multitude of GI patients they see. What's the role of a dietician with MASLD patients? If you're going to be taking on resmetirom therapy or semaglutide for MASH, assuming you get approval and so on, where does the dietician fit in? Do you try the drugs first and then say, "Well, you're not responding as well as I wanted," or do you do the dietician first? Where does a dietician fit into the whole medical management of MASH patients?
Dr Arab:
I can go first. I think dietician is kind of a foundation or the non-negotiable that you need to do, right? It's not like, okay, we're going to prescribe drugs so you don't need to worry about the diet. It doesn't work that way. I think everyone will like that, but it's not how it works. I think you need to do the lifetime changes and this is diet and exercise, and that's for every patient, independent of the stage of the fibrosis and independent if you are prescribing drugs or not. And here the diet is the Mediterranean style diet because we want to achieve weight loss. So the traditional weight loss will be 7 to 10% as a weight loss target. And then plus exercise, which is resistance plus aerobic exercise. So in my clinic, most of the patients will go to the dietician. She tries to accommodate everyone even virtually, so it's more convenient for the patient. And then we try to keep track on adherence and compliance with the diet. But I think dietician is very important.
Dr Fontana:
I agree. And we found that one and done is not good enough, like a one-time dietician consult. So we've moved for our patients with MASH who are considering for medical therapy, we're fortunate that we have dieticians who can offer a series of classes over 4 weeks or 12 weeks. And we found the patients really find that more useful as opposed to a one-time review, but over time in combination with our medical management.
The one thing, though, I think as GI and liver specialists that we can do above and beyond is also the alcohol biomarker monitoring. So tell me about that. If you start someone on resmetirom or semaglutide, do you get a baseline PEth or other biomarker? Do you get it periodically? What's the role of alcohol or is everything okay? You don't have to stop your drinking, but you're treating your liver?
Dr Abdelmalek:
I can take that. I, first of all, agree with you on the serial dietary assessments. It takes more than one session for sure. And I start drilling down with each subsequent session into what I mean. I mean, we drill down as don't drink the fruit juice, eat the fruit, no sodas, be careful about the quantity of red meat intake. And if it comes out of a box, a bag, a bottle, or a can, don't eat it. That's ultraprocessed stuff. And that really does take several sessions.
I emphasize the importance and follow their compliance with the dietary modifications in alcohol with PEth testing. You got to remember, these are very expensive medications. And I need to know with clarity, when I reassess that MR-PDFF or that CAP score, is it 30% reduction? Am I making a decision to continue treatment or not continue treatment?
The potential implications of hepatic steatosis from social alcohol use over the course of a treatment can influence those parameters and potentially influence my decision to erroneously discontinue therapy when it may actually be working. So I explain that to patients as we did with the era of hepatitis C, don't be drinking alcohol while we're trying to treat your hepatitis C. Don't be drinking alcohol. I'm trying to treat your steatotic liver disease because it can confound the outcome of that treatment.
Dr Fontana:
Okay. So I think we do have a role. If we're going to sort of own the treatment, we have to own the treatment. And again, I think alcohol is something we're all pretty comfortable managing, having conversations about that and so on.
So you mentioned, Manal, about doing a follow-up scan to see if the therapy you're prescribing is working. Tell us briefly, what should folks be thinking about? Should they only do the same scan or imaging biomarker they did before? Do they do something else afterwards? And when do they do it and how do they do it?
Dr Abdelmalek:
Yeah, I try to use the same imaging platform for which I made the decision to start treatment as a baseline, whether that's MR-based or VCTE-based. I try to use the same. I think it's hard to compare apples and oranges with regards to platform. I will perform a VCTE at 6 months and a year with resmetirom therapy to assess trends and with semaglutide at 72 to 92 weeks, a little bit longer, allow for some changes. But I'm really actually, one, interested in what's happening with hepatic steatosis, a reduction of 30% in hepatic steatosis could be a predictor of resolution of steatohepatitis and fibrosis improvement. And super-responders, if you will, complete absence of fat with treatment is very encouraging sign for me to keep going, but I'm really looking at changes in liver stiffness at the same thresholds and time points that were otherwise performed with the registration studies, MaestroNASH and ESSENCE, but allowing a little bit more time because the GLP-1 therapies are not liver directed. There are no GLP-1 receptors in the liver. They really are more of a downstream secondary effect on the liver from peripheral improvements in metabolic stress.
Dr Fontana:
JP, what do you think about the timing? Is 6 months helpful? If the VCT hasn't improved by 6 months, are you going to stop? Are you going to dose adjust? Or do you think a year is a more useful time?
Dr Arab:
You need to negotiate with the patient. Sometimes the patient wants to know soon how things are going and it's difficult to tell them come back in a year and a half or 2 years if they are on treatment. I tend to do after 6 months, but even if there's not a significant improvement, I don't stop treatment. I tell them that we need to wait a little longer and not everyone respond in the same speed and it depends on where they started. So I honestly do usually a Fibroscan after 6 months, but to make the decision where to stop it or not, we need to wait longer.
Dr Fontana:
Manal, you mentioned that a lot of patients are on incidental GLP-1s, maybe even GLP, GIP like tirzepatide for other medical reasons, and you mentioned about adding things in. So tell us a little bit about, I know you've done quite a bit of work on vitamin E. Is vitamin E something that should be in the mix? If the VCTE at 1 year is the same, it really hasn't budged. Should you be adding in vitamin E? Do you think you should be in a clinical trial? Should you add in resmetirom? I mean, what do you recommend?
Dr Abdelmalek:
So the NASH CRN did the pivotal trials with vitamin E, and in the context of the PIVENS study where they evaluated both pioglitazone, vitamin E, 800 international units of the alpha tocopherol vitamin E against placebo, vitamin E did resolve steatohepatitis. Now it didn't have an improvement on fibrosis in that 1-year study. And so vitamin E has fallen a little bit out of favor. There was concern at one point about risk of high-dose vitamin E from a cardiovascular standpoint. However, it certainly may have its role in the right patient. And if I can't get access to resmetirom— not approved, cost is prohibitive, a patient doesn't want to use injectable therapies or doesn't qualify for them—then vitamin E certainly it has its role. And I would use the same approach. I would evaluate potential response on liver aminotransferase reductions at 12 and 24 months and make a decision about 1 year worth of treatment.
And there may be data that even a lower dose of vitamin E may be beneficial as opposed to the 800. And it's certainly cheap and if it works in patients based on surrogate markers, then why not? There are responders and nonresponders to vitamin E, as we've seen responders and nonresponders to every therapeutic we studied, so it's not 100% foolproof, but a reasonable alternative medication to consider.
