As the annual Liver Meeting kicked off November 7 in Washington, DC, the American Association for the Study of Liver Diseases (AASLD) announced an update to its practice guidance for managing metabolic dysfunction-associated steatotic liver disease (MASLD).

The new guidance provides recommendations for clinicians considering the GLP-1 receptor agonist semaglutide for managing metabolic dysfunction-associated steatohepatitis (MASH) in people with moderate to advanced fibrosis, reflecting the recent accelerated approval of Wegovy for this indication. Semaglutide was initially approved for type 2 diabetes under the brand name Ozempic; Wegovy is the brand name for a higher dose used for obesity.

“This updated guidance reflects how quickly science and clinical practice are evolving and equips clinicians with the latest evidence and practical tools to manage MASLD and MASH,” said AASLD president Grace Su, MD, in a news release. “With therapies like semaglutide now available, patients and providers have new opportunities to improve liver health and overall wellness.”

MASLD and its more severe form, MASH, are responsible for a growing proportion of advanced liver disease worldwide. Estimates suggest that around a third of people in the United States have MASLD, and about 5% have MASH. Over time, the buildup of fat in the liver can lead to serious complications, including cirrhosis and liver cancer. Fatty liver disease often occurs in people with obesity, type 2 diabetes and other metabolic conditions. With only two approved medications, management still largely depends on lifestyle changes such as weight loss and exercise.

The new guidance, published in the journal Hepatology, is an update to the 2023 AASLD practice guidance on the clinical assessment and management of what was then known as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). It covers patient selection for treatment, consideration of comorbidities and monitoring of the safety and efficacy of semaglutide. 

Lifestyle modification “remains the cornerstone of MASLD/MASH management alongside semaglutide,” according to the guidance.

Patient selection may be done using noninvasive tests to assess for moderate to advanced fibrosis rather than liver biopsy, “which is impractical and unnecessary for most patients,” the guidance states.

The new recommendations reflect the latest clinical trial data, including findings from the ESSENCE study, in which adults with biopsy-proven MASH and moderate to advanced fibrosis (Stages F2 to F3) were randomly assigned to receive once-weekly semaglutide or placebo injections along with counseling about a healthy lifestyle.

As reported at last year’s Liver Meeting and in The New England Journal of Medicine, 63% of semaglutide recipients experienced resolution of steatohepatitis (liver inflammation due to fat accumulation) without worsening fibrosis, compared with 34% in the placebo group. In addition, 37% in the semaglutide group saw a reduction in liver fibrosis without worsening steatohepatitis, compared with 22% in the placebo group. About twice as many people taking semaglutide experienced both resolution of MASH and reduced liver fibrosis (33% versus 16%). What’s more, semaglutide recipients also lost more weight and showed greater improvement in biomarkers of liver health.

Findings from a secondary analysis, presented at this year’s meeting, showed that semaglutide was associated with resolution of liver injury and a trend toward improvement in fibrosis across a spectrum of weight-loss thresholds and in people of both sexes and various ages, races and ethnicities, suggesting the benefits are not solely attributable to weight loss.

Wegovy is not approved for the treatment of people with MASH who have already progressed to cirrhosis (Stage F4). Patients with compensated cirrhosis who are receiving semaglutide for another indication approved by the Food and Drug Administration (FDA) should be monitored carefully, according to the guidance. Combining semaglutide with resmetirom (Rezdiffra), the first medication approved for MASH, has not been adequately studied, but some experts think a combination approach may be needed to both reduce liver fat and lessen liver damage in people with advanced fibrosis or cirrhosis.

“This is an exciting time in the MASH field," said Meena Bansal, MD, of the Ichan School of Medicine at Mount Sinai. “With multiple FDA-approved therapies, AASLD is committed to leading the way in providing timely practical recommendations to clinicians on patient selection for treatment and monitoring for safety and efficacy.”


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