What is MASH?

Metabolic Dysfunction-Associated Steatohepatitis (MASH) represents an advanced form of nonalcoholic fatty liver disease characterized by liver inflammation due to excessive fat accumulation. Without intervention, this condition can progressively lead to severe outcomes, including liver fibrosis, failure, or even hepatocellular carcinoma.

Commonly developing in individuals with metabolic disorders—such as obesity, hyperlipidemia, or type 2 diabetes—MASH affects nearly 15 million people across the United States, a figure likely underreported due to difficulties in diagnosis.

The Complexity of Treatment

Treating MASH poses unique challenges due to the intricate interplay of various metabolic pathways that culminate in liver fat buildup, inflammation, and potential fibrosis. As Dr. Veeral Ajmera, an associate professor of medicine at UC San Diego School of Medicine, explains, “It takes time to identify the right pathways to target, to reverse that process, and to determine the best way to measure improvement in trials.”

Moreover, some patients may possess genetic predispositions that complicate treatment efforts. Dr. Kirti Shetty, medical director of liver transplantation at the University of Maryland, emphasizes that effective management must intersect multiple treatment pathways alongside recommended lifestyle modifications.

Current Therapeutic Options

FDA-Approved Treatment

The approval of Rezdiffra (resmetirom) by the FDA marks a significant milestone as the first pharmaceutical option specifically for MASH treatment. This oral medication functions by activating a thyroid hormone receptor in the liver, aiming to reduce fat accumulation and, in some instances, improve the hepatic condition. However, Dr. Shetty points out that Rezdiffra may not yield beneficial results for all patients.

Clinical trials have shown mixed outcomes, with about 26% of participants taking the 80 mg dose of Rezdiffra experiencing resolution of MASH, compared to less than 10% in the placebo group. Therefore, continuous evaluation for at least a year is necessary to assess the medication’s efficacy.

Investigational Treatments Under Development

The presence of an FDA-approved drug can catalyze further research into additional therapies for MASH. Dr. Wajahat Mehal from Yale School of Medicine highlights this potential, stating, “Pharmaceutical companies will have a better understanding of the thresholds they must meet to get future approvals.” This optimism extends to new medications aimed at managing MASH, including GLP-1 receptor agonists like Mounjaro and Wegovy, which facilitate weight loss—critical for patients with MASH.

While promising, the effectiveness of these drugs in reversing existing MASH is still being investigated. Nonetheless, evidence suggests that early intervention and lifestyle changes remain paramount in preventing progression to MASH.

Preventive Measures

Preventive strategies play a crucial role in combating MASH. Experts, including Dr. Bubu Banini of Yale School of Medicine, recommend a balanced diet rich in fruits and vegetables, regular physical activity, and abstaining from alcohol as effective measures to safeguard liver health. For individuals with a higher body weight, losing 5-10% of body mass can significantly decrease the risk of liver fat accumulation.