Addressing Unmet Needs in Cirrhotic MASH with Metabolic Surgery, with Sobia Laique, MD

In March 2024, resmetirom (Rezdiffra) made history when it became the first drug to earn US Food and Drug Administration approval for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), offering a long-awaited pharmacologic treatment option for a patient population once thought to be untreatable.¹

Despite its undeniable impact on the field of hepatology, the approval of resmetirom did not address the unmet needs faced by all patients with MASH. Indicated specifically for those with noncirrhotic MASH and moderate to advanced fibrosis, resmetirom is not currently approved for those with MASH and cirrhosis.¹

“The FDA’s approval of resmetirom as the first therapeutic agent for fibrotic, noncirrhotic MASH truly marked a significant milestone in the field,” Sobia Laique, MD, a gastroenterologist and transplant hepatologist at Cleveland Clinic, told HCPLive. “However, we have to acknowledge there are considerable unmet clinical needs remaining, particularly for our patients with MASH-related cirrhosis, because we currently don't have any pharmacological therapies that are specifically approved to treat or reverse cirrhosis associated with MASH.”

In the absence of an FDA-approved drug for these patients, Laique described the different facets of disease management clinicians must be aware of, including optimizing behavioral health; lifestyle interventions; improving cardiometabolic health; mitigating risk factors for disease progression; and monitoring for complications of cirrhosis.

In patients with compensated cirrhosis, she emphasized the importance of preventing progression to decompensated cirrhosis, especially in patients with comorbid obesity.

“The added component of obesity itself increases their risk of decompensation annually by 3-fold, which is substantial,” Laique explained. “This highlights the critical need for obesity management in patients with compensated MASH cirrhosis.”

Recognizing the known impact metabolic surgery has on weight loss and the management of cardiometabolic comorbidities, she described its potential benefit for patients with obesity and compensated MASH cirrhosis and hypotheses about its ability to prevent major adverse liver outcomes (MALO) and hepatic decompensation, which were explored in the Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) study.²

Indeed, results highlight a 72% reduced risk of incident MALO and an 80% reduced risk of progression to decompensation with metabolic surgery versus nonsurgical treatment in patients with compensated MASH-related cirrhosis and obesity.²

References

1. ^{Brooks A. Resmetirom (Rezdiffra) Receives Historic FDA Approval for Noncirrhotic NASH. HCPLive. March 14, 2024. Accessed February 3, 2025. https://www.hcplive.com/view/resmetirom-rezdiffra-receives-historic-fda-approval-for-noncirrhotic-nash}
2. ^{Brooks A. Metabolic Surgery Improves Long-Term Liver Outcomes in MASH-Related Cirrhosis. HCPLive. January 28, 2025. Accessed February 3, 2025. https://www.hcplive.com/view/metabolic-surgery-improves-long-term-liver-outcomes-mash-related-cirrhosis}