Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Metabolic dysfunction-associated steatohepatitis (MASH)—previously known as nonalcoholic steatohepatitis (NASH)—occurs when fat buildup in the liver causes liver inflammation, damage, and fibrosis (scarring). MASH is a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD).

About 1.5-6.5% of adults in the United States have MASH, and early stages often cause few or no symptoms.

Lifestyle changes may help reverse mild cases of MASH, while more severe cases may require medication or surgery. A hepatologist (a doctor specializing in liver diseases) can diagnose MASH.

MASH does not often cause symptoms in its early stages. If symptoms do appear, they may include:

• Sharp, dull, or aching pain in your upper abdomen
• Fatigue
• Thirst
• Bloating
• Sleep issues

As the disease progresses, other symptoms may occur due to more liver scarring and inflammation. These symptoms include:

• Nausea
• Vomiting
• Jaundice, or yellowing of the skin and the whites of your eyes
• Ascites, or fluid buildup and swelling in your abdomen
• Itchy skin
• Easy bleeding, including bruising
• Spider veins
• Mental confusion

When fat builds up in your liver, it can cause liver inflammation and damage characteristic of MASH. However, experts aren’t sure exactly what causes the fat buildup and inflammation.

Risk Factors

While an exact cause of metabolic dysfunction-associated steatohepatitis isn’t clear yet, experts have determined a few factors that may increase the risk. These risk factors include:

• Body weight: Research suggests a body mass index (BMI) over 30—which indicates obesity in some people—is associated with a much higher risk of MASH than those with a lower BMI. Rapid or excessive weight loss may also increase the risk.
• Other health conditions: Type 2 diabetes, prediabetes, insulin resistance, metabolic syndrome, high cholesterol or triglycerides, and obstructive sleep apnea may increase risk of MASH. 
• Ethnicity: People of Hispanic or Asian ethnicity tend to have a higher risk of MASH.
• Age: MASH is more common in adults, though children may also develop it. The risk increases after age 50.

MASH often causes no symptoms, so your healthcare provider may first discover signs of liver damage (such as increased liver enzymes in your blood or an enlarged liver) during routine testing or while examining you for other conditions.

If your provider suspects MASH, they may ask about your current medications, diet, alcohol intake, and health history. They will also do a physical examination to check for signs of enlarged liver or jaundice, and they may check your height and weight to calculate your BMI.

They may also recommend additional tests to get more information. These tests include:

• Blood tests: Blood tests can help detect liver damage and inflammation. Your healthcare provider may look at your liver enzymes, blood fat levels, and indicators of scarring with lipid function tests, lipid profile tests, and fibrosis assessments.
• Imaging tests: Imaging tests such as computerized tomography (CT) scans, magnetic resonance imaging (MRI), and ultrasounds can take pictures of your liver and reveal inflammation or fibrosis.
• Liver stiffness tests: These specialized imaging tests can help determine the extent of fibrosis by measuring the stiffness of your liver. The more scarring present, the stiffer your liver will be. Common stiffness tests include transient elastography and magnetic resonance elastography (MRE).

Your healthcare provider may also recommend a liver biopsy—the only true diagnostic test for MASH. Your provider will insert a needle into your liver and collect a sample of liver tissue, which will be examined under a microscope for fat and signs of damage.

Stages of MASH

Metabolic dysfunction-associated steatohepatitis may occur in four stages, which differ in levels of scarring and damage:

• Stage 1: Mild fibrosis
• Stage 2: Moderate fibrosis
• Stage 3: Severe fibrosis
• Stage 4: Cirrhosis, or very severe and permanent liver scarring

Your healthcare provider may recommend several lifestyle changes to help decrease fat and heal your liver. In more advanced MASH, you may also need medication or surgery.

Lifestyle Approaches

Lifestyle approaches to help reduce fat and inflammation in your liver include:

• Lose any excess weight through methods you and your healthcare provider decide are appropriate for you
• Eat a nutritious and balanced diet that limits sugar and saturated fat
• Regularly exercise as recommended
• Manage your diabetes, if you have it
• Manage your cholesterol if your levels are too high
• Be mindful when taking some dietary supplements and medications, as they may harm your liver; your healthcare provider or pharmacist can discuss the risks with you

Medication

The U.S. Food and Drug Administration (FDA) has approved Rezdiffra (resmetirom), the first drug approved for treating MASH with moderate or severe fibrosis. Your healthcare provider may prescribe it along with recommended lifestyle approaches.

If you also have metabolic syndrome, your healthcare provider may recommend medications such as diabetes medication, cholesterol medication, or weight loss medication to help manage it.

Surgery

In severe cases—such as if MASH progresses to cirrhosis and liver failure—healthcare providers may recommend a liver transplant. This surgery involves removing your damaged liver and replacing it with a healthy liver from a donor. In cases of liver failure from cirrhosis, a liver transplant may save your life.

The same lifestyle approaches that may help treat MASH can also help prevent the condition. It’s important to make choices—in your diet; exercise habits; and use of alcohol, supplements, and medication—that promote good liver health.

MASH can lead to other conditions, especially if left untreated. Conditions related to MASH include:

• Cirrhosis: This condition happens when scar tissue replaces healthy liver tissue, preventing the liver from working as it should. About 20% of MASH cases progress into cirrhosis over several years.
• Liver cancer: People with MASH-related cirrhosis are at a higher risk of developing liver cancer.
• Liver failure: Unmanaged cirrhosis may lead to liver failure, when your liver is permanently damaged and stops working.
• Cardiovascular disease: Severe cases of MASH may increase the risk of heart attack and stroke.

Most cases of MASH are mild, and you may be able to reverse them through lifestyle changes such as weight loss, diet, and regular exercise.

If left untreated, fibrosis can progress to cirrhosis, which can lead to permanent liver damage and liver failure. Early screening, diagnosis, and treatment are key to slowing disease progression and preventing complications.