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MASLD and MASH Treatment
An Expert Focus on the Treatment of MASLD/MASH

Released: January 10, 2024

Expiration: January 10, 2025

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Key Takeaways
  • In the setting of MASH, the risk of adverse liver-related outcomes primarily is associated with the degree of liver fibrosis.
  • The goal of MASLD and MASH treatment ideally is resolution of MASH and reversal of liver fibrosis through the mainstay of lifestyle modifications and management of obesity and diabetes.
  • The use of GLP-1 RAs has been associated with decreased liver enzymes, resolution of MASH, and fibrosis regression.

The advanced form of metabolic dysfunction–associated steatotic liver disease (MASLD), metabolic dysfunction–associated steatohepatitis (MASH), is a leading cause of chronic liver disease that may progress to death or require liver transplantation. In the setting of MASH, the risk of adverse liver-related outcomes primarily is associated with the degree of liver fibrosis. Advanced fibrosis and cirrhosis, in particular, place patients at elevated risk of liver-related complications. On the other hand, regression of fibrosis through effective medical or lifestyle interventions has been demonstrated to decrease this risk.

Therefore, the goal of MASLD and MASH treatment ideally is resolution of MASH and reversal of liver fibrosis. In the absence of FDA-approved therapies for MASH, the mainstay of treatment involves lifestyle modification, weight loss, and pharmacotherapy directed toward contributing comorbidities including diabetes and obesity. Early intervention is essential to avoid the aforementioned risk of adverse events associated with advanced stages of liver fibrosis.

In terms of effective interventions in MASLD and MASH, weight loss clearly has been shown to affect their natural history. The percentage of body weight loss required to see improvement varies based on the presence and severity of an individual’s fibrosis. For example, losing 3% of body weight can reverse simple steatosis, whereas 10% or more weight loss is needed to reverse established fibrosis. Approaches to losing weight should be individualized and are most successful if they involve a structured weight loss program consisting of an energy-restricted diet with or without a combined exercise program, pharmacotherapy including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or bariatric surgery or procedures.

Increased physical activity such as 150-300 minutes of moderate aerobic exercise weekly or resistance training 3 nonconsecutive days per week can decrease hepatic steatosis and liver enzyme levels, even in the absence of weight loss. When weight loss is the goal, more intense exercise is superior to minimal or low intensity. Example dietary changes beyond reduced caloric intake can include adoption of a Mediterranean diet rich in vegetables, fruits, high-fiber cereals, nuts, fish, and olive oil while limiting simple sugars and red or processed meats. This diet has been associated with reduced hepatic steatosis, improved insulin sensitivity, and lower overall mortality.

Medications from the GLP-1 RA class increasingly are prescribed for management of diabetes and obesity. Their mechanism of action involves augmenting meal-induced β-cell insulin production and slowing gastric emptying, leading to increased satiety and central nervous system signaling to reduce food intake. Their use has been associated with decreased liver enzymes, resolution of MASH, and fibrosis regression. Additional classes of medications, such as sodium-glucose cotransporter 2 inhibitors and thiazolidinediones, also may be employed for the treatment of comorbid diabetes given their favorable effect on liver fat and, in the case of pioglitazone, inflammation/fibrosis.

Personalized MASLD/MASH management begins with an assessment of risk of fibrosis-related complications, dividing affected patients into low, intermediate, and high risk based on serum- or imaging-based noninvasive fibrosis assessments or liver biopsy when performed. Lifestyle interventions including weight loss are indicated for all risk groups. In the intermediate- and high-risk populations, a greater emphasis is placed on pharmacotherapy aimed at diabetes management and/or weight loss, particularly involving GLP-1 RAs and pioglitazone.

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