MASH, an advanced form of nonalcoholic fatty liver disease, refers to the inflammation of the liver caused by fat buildup. Over time, this inflammation can lead to scarring, liver failure, or even cancer.
MASH, which stands for metabolic dysfunction-associated steatohepatitis, often develops in people with underlying metabolic conditions such as obesity, high cholesterol, or type 2 diabetes.
Nearly 15 million people in the United States have MASH, but the condition is likely underdiagnosed.
MASH is a difficult condition to treat because it’s the “convergence of a lot of metabolic pathways that manifest in the liver with liver fat, inflammation, and eventually fibrosis,” said Veeral Ajmera, MD, an associate professor of medicine at the UC San Diego School of Medicine who treats liver disease.
“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,” Ajmera added.
In addition to the different pathways that could lead to MASH, some people may have a genetic predisposition to the condition, according to Kirti Shetty, MD, a professor of medicine and medical director of liver transplantation at the University of Maryland School of Medicine.
“Optimal management will require not just the manipulation of one pathway but multiple ones, and treatment has to be combined with lifestyle measures,” Shetty told Verywell.
Only One FDA-Approved Treatment Available
The very first drug to treat MASH, Rezdiffra (resmetirom), was approved by the Food and Drug Administration (FDA) last year. Until then, physicians primarily relied on lifestyle changes—such as weight loss and regular exercise—to manage the condition.
Rezdiffra is a daily oral pill that activates a thyroid hormone receptor in the liver to reduce fat build-up and, in some patients, improve the disease. While Rezdiffra marks an important advancement in MASH treatment, it’s not effective for everyone, Shetty said.
A phase 3 clinical trial found that about 26% of participants who received 80 milligrams of Rezdiffra and 30% who received 100 milligrams had MASH resolution and no worsening of liver scarring, compared to less than 10% of those who received only a placebo.
“Rezdiffra is effective in about a third of patients,” Shetty said. “So there is certainly a need for more effective treatments.”
Currently, patients have to take Rezdiffra for a year to determine if the drug has worked well for them.
New MASH Treatments in the Pipeline
Having even one FDA-approved drug important for other MASH therapies down the line, said Wajahat Mehal, MD, a professor of medicine specializing in digestive diseases at the Yale School of Medicine.
“Pharmaceutical companies will have a better understanding of the thresholds they must meet to get future approvals,” Mehal said. “This makes them more enthusiastic about continuing drug development in this area. And there are many promising medications coming along.”
GLP-1 drugs such as Mounjaro and Wegovy are being studied to treat MASH because typically, if MASH patients can lose 10-11% of their body weight, their liver condition improves, Mehal said.
Emerging research also shows that GLP-1 drugs may help stop liver disease from progressing into MASH.
“But once someone has MASH, these drugs have not yet been proven to reverse it,” Mehal said. However, he added that early data from clinical trials are showing promising results.
The best available treatment for MASH right now is prevention. People can avoid developing liver disease by eating a healthy diet with several servings of vegetables and fruits a day, exercising regularly, and avoiding alcohol use, said Bubu Banini, MD, an assistant professor of medicine at the Yale School of Medicine.
For people with a higher weight, losing 5–10% of their body weight could help decrease the risk of excess fat buildup in the liver.
What This Means For You
If you have type 2 diabetes, high cholesterol, or a higher body weight, you may be at increased risk for MASH, a serious liver condition that’s often underdiagnosed. Lifestyle changes like improving diet and increasing physical activity are essential to managing liver disease. Talk to your healthcare provider if you’re concerned about your liver health.Pending Queue
Understanding Metabolic Dysfunction-Associated Steatohepatitis (MASH)
Metabolic Dysfunction-Associated Steatohepatitis (MASH) is an advanced form of nonalcoholic fatty liver disease characterized by inflammation due to fat accumulation in the liver. If not managed properly, it can lead to severe complications such as liver failure or cancer.
Who is Affected by MASH?
Approximately 15 million individuals in the United States are estimated to have MASH, though it remains largely underdiagnosed. This condition often arises in those with related metabolic disorders, including obesity, high cholesterol, or type 2 diabetes.
Challenges in Treatment
Treating MASH poses significant challenges due to its complex nature. “It’s the convergence of a lot of metabolic pathways that manifest in the liver with liver fat, inflammation, and eventually fibrosis,” explains Dr. Veeral Ajmera, an expert in liver disease at UC San Diego School of Medicine. Identifying the right treatment pathways takes time and requires understanding how to measure improvements in patients effectively.
Genetic Factors
Some individuals may also have a genetic predisposition to MASH, which complicates the management of the disease. According to Dr. Kirti Shetty, a professor of medicine at the University of Maryland, optimal treatment strategies cannot focus on a single pathway but must consider a multimodal approach, including lifestyle modifications.
FDA-Approved Treatment: Rezdiffra
The FDA recently approved Rezdiffra (resmetirom), marking its first drug for MASH treatment. Prior to this, management primarily relied on lifestyle changes aimed at weight loss and physical activity. Rezdiffra is taken as a daily oral medication aimed at activating thyroid hormone receptors in the liver to mitigate fat accumulation and potentially improve liver health. However, it is effective in only about a third of patients, as noted by Dr. Shetty, thus underscoring the need for additional treatment options.
Clinical Trial Insights
A phase 3 clinical trial revealed that around 26% of participants on a high dose of Rezdiffra achieved MASH resolution and experienced no worsening of liver scarring, compared to less than 10% of those on a placebo.
Future of MASH Treatments
The approval of Rezdiffra is seen as a breakthrough that may stimulate the development of additional therapies. Dr. Wajahat Mehal at Yale School of Medicine highlights that greater clarity on approval standards may encourage pharmaceutical companies to develop further medications targeting MASH.
Emerging Research
Several medications, such as GLP-1 receptor agonists (e.g., Mounjaro and Wegovy), are being evaluated for their potential to manage MASH. These drugs may help patients lose the necessary weight—typically 10-11% of body weight—to improve their liver condition. However, current evidence does not yet support their efficacy in reversing established MASH.
Prevention is Key
The best approach to combat MASH remains prevention through healthy lifestyle choices. A diet rich in fruits and vegetables, regular physical activity, and avoidance of alcohol can significantly reduce the risk of developing liver disease. Additionally, for individuals with excess body weight, losing just 5-10% can reduce liver fat accumulation.
Conclusion
If you are at risk for MASH due to conditions like type 2 diabetes, high cholesterol, or obesity, it is crucial to engage with your healthcare provider about your liver health and consider proactive lifestyle changes.
