MASLD and MASH in Focus: Clinical Priorities and Promising Pathways

Announcer:
This is Clinician’s Roundtable on ReachMD. On this episode, Dr. Peter Buch will be sharing insights on our evolving treatment approach to metabolic dysfunction-associated steatotic liver disease and steatohepatitis, also known as MASLD and MASH. Dr. Buch is a board-certified clinical gastroenterologist and Associate Professor at Frank H. Netter, MD School of Medicine at Quinnipiac University. Let’s hear from him now.

Dr. Buch:
When we’re talking about MASLD, we always start with the basics—basically weight loss and exercise. And I just wanted to share the statistics, which are really pretty impressive. If a patient loses 10 percent of their body weight, they may be reducing MASLD by 97 percent, and that’s why it’s so important for us to make that recommendation to patients. Also interesting in this process is the fact that even exercise alone without weight loss may have some direct bearing with regard to improvement, but certainly nothing like weight loss itself.

It’s very important to keep in mind that when we’re talking about metabolic syndrome, the direct and early relationship of metabolic syndrome is cardiovascular disease. Cardiovascular disease occurs much earlier than any sort of liver consequence in this disease.

So now let’s move on to metabolic steatohepatitis—MASH. MASH is a progression from MASLD. It occurs in 25 percent of patients with MASLD. MASH means protein and collagen deposition, whereas cirrhosis—the next part of this process—is significant scarring, which occurs after there’s been plenty of fibrosis.

So the standard care of MASH is weight loss, but also medication. And let’s talk a little bit about the medications that are available for MASH. There are two currently available medications for MASH. One is called resmetirom. Resmetirom is an oral liver-directed thyroid hormone receptor beta-selective agonist. What this means is that this medication causes fat breakdown and reduction in inflammation in the liver.

The MAESTRO study, which was the key study, demonstrated that at 12 months, there was a 25 percent reduction in one fibrosis stage, which is pretty impressive. Resmetirom has an excellent safety profile, with diarrhea occurring in about 30 percent of the patients. And thyroid monitoring is necessary during treatment.

The second therapy that we’re going to be talking about is semaglutide, which everybody out there should be very familiar with. The trial that was undertaken was the ESSENCE trial. 63 percent of patients in that trial had MASH resolution. That’s pretty impressive. And 36 percent showed a one-stage reduction in fibrosis over 72 weeks.

There’s no comparison of resmetirom and semaglutide, and we don’t know if MASH will recur if resmetirom is stopped, and we don’t have data yet on the use of both resmetirom and semaglutide. Many clinicians at this point are considering resmetirom for patients who do not respond to semaglutide or who have an adverse reaction to it.

In conclusion, I think we should think about what other medicines that are out there which would have a potential benefit for, MASH, and they include the other injectable GLP-1 agonists that we’re all familiar with, but it also includes the potential of using oral GLP-1 agonists that are currently being worked on. And the future with regard to MASH treatment is incredibly exciting. We’re looking forward to those developments in the very near future.

Announcer:
That was Dr. Peter Buch discussing current strategies for managing MASLD and MASH. To access this and other episodes in this series, visit Clinician’s Roundtable on ReachMD.com, where you can be part of the knowledge. Thanks for listening!