New Frontiers in MASH Treatment and Prevention

Metabolic dysfunction-associated steatohepatitis (MASH) is a severe form of nonalcoholic fatty liver disease (NAFLD) characterized by liver inflammation due to fat accumulation. Over time, this can lead to serious consequences including scarring, liver failure, and even cancer. Individuals with conditions like obesity, high cholesterol, and type 2 diabetes are particularly susceptible to developing MASH.

Currently, nearly 15 million Americans are believed to have MASH, though it often goes undiagnosed. According to Dr. Veeral Ajmera, an associate professor of medicine at UC San Diego, MASH is challenging to treat because it involves multiple metabolic pathways impacting the liver, leading to inflammation and fibrosis. He emphasized the complexity of identifying the right pathways to target for treatment and measuring improvement in clinical trials.

Dr. Kirti Shetty, a liver transplantation expert at the University of Maryland, noted that genetic predisposition may also play a role, necessitating a multi-faceted approach combining medication with lifestyle changes for effective management.

The FDA approved the first drug for MASH, Rezdiffra (resmetirom), last year. Prior to this, lifestyle modifications, such as weight loss and exercise, were the mainstay of treatment. Rezdiffra, an oral pill, works by activating a thyroid hormone receptor in the liver to reduce fat buildup and potentially improve the condition for some patients. Despite this breakthrough, Dr. Shetty pointed out that it only benefits about a third of patients.

Clinical trials have shown that around 26% of participants taking 80 mg of Rezdiffra and 30% taking 100 mg achieved MASH resolution without worsening liver scarring, compared to less than 10% in the placebo group. Patients typically need to take Rezdiffra for a year to assess its effectiveness.

Exciting developments in MASH treatment are underway, with other promising medications in the pipeline. Dr. Wajahat Mehal from Yale School of Medicine believes that the approval of Rezdiffra will encourage pharmaceutical companies to pursue further drug developments. GLP-1 drugs like Mounjaro and Wegovy are being researched for their potential to aid in weight loss, which can improve liver conditions in MASH patients.

Though not yet proven to reverse MASH, these GLP-1 drugs may prevent progression to more severe liver disease. Dr. Mehal is optimistic, noting promising early results from clinical trials.

In the meantime, the best approach to combat MASH is prevention. Dr. Bubu Banini from Yale School of Medicine stresses the importance of a healthy diet rich in fruits and vegetables, regular exercise, and alcohol avoidance. For those with higher weight, losing 5% to 10% of body weight may significantly reduce the risk of liver fat accumulation.