Metabolic dysfunction-associated steatohepatitis (MASH)

June 2, 2024

Metabolic dysfunction-associated steatohepatitis (MASH), formerly referred to as NASH), is a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by inflammation and liver cell damage. MASH occurs when excess fat accumulates in the liver, leading to inflammation and injury. The exact cause is not fully understood, but it is believed to be a multifactorial disease with a combination of genetic, metabolic, and environmental factors playing a role.1

Man with abdominal pain

The prevalence of MASH is increasing worldwide, largely due to the rising rates of obesity and metabolic disorders. It is estimated that up to 25% of the adults in the U.S. may have MASLD, and approximately 20% of these individuals have progressed to MASH1. MASH is more common in individuals with certain risk factors, such as obesity, type 2 diabetes, high cholesterol, and high blood pressure, as well as Hispanic or Asian ethnicity, age over 40, and postmenopause.1

Symptoms of MASH can be nonspecific and may include fatigue, abdominal discomfort, and mild jaundice. However, many individuals are asymptomatic and may only be diagnosed through routine liver function tests or imaging studies. Diagnosis requires a liver biopsy to assess the degree of inflammation, liver cell damage, and fibrosis.

The management of MASH involves lifestyle modifications, including weight loss, regular exercise, and a healthy diet. Studies have shown that a weight loss of 10% or more has been shown to improve liver histology, reduce disease progression and in some cases reverse liver fibrosis.2 In addition, controlling underlying metabolic conditions, such as diabetes and high cholesterol, is important in managing this condition.

Woman with stomach pain

In severe cases, up to 20% of patients will progress to cirrhosis over a 15-year time period and liver transplantation may be necessary.3 However, prevention and early intervention are key in managing and preventing disease progression. Regular monitoring of liver function, lifestyle modifications, and close collaboration with healthcare providers are essential in the management of MASH.

Until recently, there were no therapeutic pharmaceutical treatments to manage MASH. On March 16, 2024, the FDA approved the first medication treatment for this condition, Resmetirom (Madrigal Pharmaceuticals). It is approved as an oral formulation for use in conjunction with diet and exercise for adults with noncirrhotic MASH with moderate to advanced liver fibrosis (stages F2-F3 fibrosis). Clinical trials have shown a 50-60% reduction in liver fat associated with a 64% MASH resolution.4 The company said it expects Resmetirom to be available through a limited specialty pharmacy network in the United States in April.


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  1. “Metabolic Dysfunction-Associated Steatohepatitis,” The Cleveland Clinic, accessed March 11, 2024,
  2. “Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis,” Gastroenterology, accessed March 11, 2024,
  3. “Aggressive non-alcoholic steatohepatitis following rapid weight loss and/or malnutrition,” Mod Pathol, accessed March 17, 2024,,understood%20and%20pathologic%20features%20have%20not%20been%20well-characterized.
  4. “Analysis of the Non-Alcoholic Steatohepatitis (NASH) Drug Pipeline & Market: Sizing Up the First Wave,” Pharmaceutical Online, accessed March 11, 2024,