New Hope and Persistent Challenges for MASH Treatment: Naim Alkhouri, MD

Over the past decade, the treatment landscape for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) has undergone significant transformation, explained Naim Alkhouri, MD, FAASLD, DABOM, chief medical officer, chief of transplant hepatology, and director of the Steatotic Liver Program at Arizona Liver Health. The recent approval of resmetirom (Rezdiffra) for noncirrhotic MASH has marked a major advancement in disease management. However, addressing the needs of patients with severely cirrhotic MASH remains a key challenge that clinicians are now aiming to overcome.

In the first installment of his interview with The American Journal of Managed Care®, Alkhouri discussed recent advances in MASH research, the potential of both emerging and FDA-approved treatments, and the clinical challenges researchers may face as they work to further progress in the field.

This transcript has been lightly edited; captions were auto-generated.

Transcript

What would you say are the most pressing scientific or clinical challenges related to MASH that researchers are grappling with today?

We've made a lot of progress in terms of developing new therapeutics for MASLD and MASH over the last decade. We have now 1 FDA-approved medication called resmetirom, and we are anticipating the FDA approval of semaglutide at the end of this year.

However, we have many unmet needs in the field, including treatment of patients with mass cirrhosis, this is stage four fibrosis. We are developing several therapeutics for this patient population. They have the highest disease burden on the highest chances of developing clinical outcomes. We are also trying to validate noninvasive tests that can diagnose the disease stage, monitor treatment response, and also predict long-term prognosis. We've made a lot of advancements in this area. We call it NITs, noninvasive tests, but we still need to finesse these NITs and tackle some issues related to the positive predictive value and make sure that we identify the proper patients for treatment.

We also have issues with the efficacy of the current medications. They are helpful. They lead to mass resolution and fibrosis improvement, but the delta improvement from placebo is relatively small, and we can definitely improve on it. Now we are looking at maybe a delta between 20%-30% range on MASG resolution; and for fibrosis improvement, it's between 10%-15%. I think with combination therapy and potentially neurotherapeutic agents we can improve that response rate.