Metabolic Dysfunction-Associated Steatohepatitis (MASH)

What is metabolic dysfunction-associated steatohepatitis (MASH)?

Steatohepatitis is an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD). If you have steatotic (fatty) liver disease, your body has begun storing excess fat in your liver. This doesn’t always cause problems for people. But when it does, it’s called steatohepatitis.

“Hepatitis” means inflammation of the liver, and “steato” means from fat. Chronic inflammation can damage your liver, causing scarring of the tissues. If scarring progresses, it can lead to cirrhosis and eventually, liver failure.

Liver disease is frequently associated with chronic alcohol use. But if you have MASLD, you have this condition despite low alcohol use. Researchers aren’t sure why this occurs, but high levels of fats in the blood are a common factor.

Metabolic dysfunction-associated steatohepatitis (MASH) is the advanced stage of MASLD. It means that your condition is causing inflammation and damaging your liver — again, despite low alcohol use.

Previously, MASH was known as non-alcohol related steatohepatitis (NASH).

How common is this condition?

Metabolic dysfunction-associated steatotic liver disease is common. Researchers estimate that up to 25% of adults in the U.S. have MASLD, but only 20% of those with MASLD have MASH.

What are some risk factors for the development of MASLD and MASH?

Healthcare providers don’t know why some people with MASLD develop MASH and some don’t. They don’t entirely know why people get MASLD. Some people seem to get it for no apparent reason. There may be a genetic factor.

However, MASLD and MASH are more common in people who have certain conditions associated with high blood lipid levels. Studies suggest that 30% to 60% of people with Type 2 diabetes have MASLD. Up to 75% of people with overweight and up to 90% of people with class III obesity have MASLD.

Is metabolic dysfunction-associated steatohepatitis (MASH) life-threatening?

MASH in itself isn’t necessarily life-threatening, but the presence of MASH with other risk factors such as older age and diabetes may increase the risk of progression to end-stage liver disease, which is a terminal condition.

Liver disease progresses slowly. Not everyone with steatohepatitis will progress to cirrhosis, which is late-stage, severe liver disease. However, liver disease can progress without noticeable symptoms. It’s possible to have a severe condition before you become aware of it.

In addition to having an increased risk for liver-related illness, people with MASH also tend to have a higher risk of suffering from a heart attack or stroke due to the presence of other comorbidities (when there are two or more medical conditions present) such as diabetes, high blood pressure and coronary artery disease.

Is metabolic dysfunction-associated steatohepatitis (MASH) reversible?

If you have mild-to-moderate liver damage, you can still stop it from progressing and even reverse some of the damage with healthy lifestyle changes. As steatohepatitis progresses, however, and more liver tissue turns to scar tissue, the liver begins to lose blood supply. This causes irreversible cell death.

What causes metabolic dysfunction-associated steatohepatitis (MASH)?

It’s not alcohol, but what is it? Researchers suspect it has something to do with fat levels in your blood, although not every case seems to fit this profile. Still, there’s a definite pattern of related risk factors leading to MASH.

Common risk factors include:

• Overweight (BMI, or body mass index, of 25+).
• Metabolic syndrome.
• High cholesterol.
• High blood pressure.
• High blood sugar.
• Insulin resistance and diabetes.
• Underactive thyroid.
• Underactive pituitary gland.

Additional risk factors include:

• Hispanic or Asian ethnicity.
• Being over 40 years old.
• Postmenopause.
• Polycystic ovary syndrome.
• Severe protein deficiency.
• Rapid weight loss.

What are the symptoms of metabolic dysfunction-associated steatohepatitis?

In earlier stages, many people don’t have any symptoms.

The most common symptoms of moderate MASH are:

• An ache in your upper right abdomen, where your liver is.
• Weakness and fatigue.
• Loss of appetite.
• Unexplained weight loss.

More advanced stages may begin to resemble the symptoms of cirrhosis. You may notice:

• Yellowing of your skin and the whites of your eyes (jaundice).
• Easy bruising and bleeding.
• Your belly becomes swollen with fluid (ascites).
• Swelling in your legs and feet (edema).
• Enlarged liver or enlarged spleen.
• Enlarged, spider-like blood vessels under your skin.
• Enlarged veins in your esophagus, which can bleed.
• Portal hypertension, which can cause intestinal bleeding.
• Persistent itchiness (pruritus).
• Confusion, drowsiness and slurred speech (hepatic encephalopathy).

What are the possible complications of metabolic dysfunction-associated steatohepatitis (MASH)?

The primary risk of MASH is progressive fibrosis leading to cirrhosis of the liver. This occurs in 5% to 12% of people with MASH.

Cirrhosis is associated with an increased risk of liver cancer. Most people with liver cancer have cirrhosis. MASLD and MASH are also both associated with an increased risk of cardiovascular disease and Type 2 diabetes. It works both ways: having these conditions makes you more likely to have metabolic dysfunction-associated steatohepatitis, and vice versa.

How is metabolic dysfunction-associated steatohepatitis (MASH) diagnosed?

Your healthcare provider will begin by examining you for signs of liver disease. They’ll ask you about your health conditions and lifestyle, including alcohol consumption. If they suspect MASLD or MASH, they’ll proceed to test for it in a few different ways.

Blood tests

By taking a sample of your blood to the lab, healthcare providers can test it to help identify liver damage.

• Liver function tests check for evidence of liver inflammation, such as elevated liver enzymes and other metrics.
• Fibrosis assessment tests can help healthcare providers estimate the level of scarring, or fibrosis.
• A lipid panel measures levels of fats in your blood.
• Other tests can help rule out other possible causes of hepatitis.

Imaging tests

Your healthcare provider will want to look at your liver for signs of inflammation, swelling and scarring. They may use:

• Abdominal ultrasound, a noninvasive test that produces images using sonography (sound waves).
• CT scan (computed tomography scan), a more intensive, but more accurate, imaging test that produces 3D X-rays.

Liver stiffness tests

These are modified imaging tests that help measure the level of stiffness and fibrosis in your liver.

• FibroScan® is a specialized kind of ultrasound machine that can measure liver scar tissue and fat.
• Magnetic resonance elastography (MRE) combines ultrasound and MRI imaging to create a visual map of liver fibrosis.

Liver biopsy

To confirm metabolic dysfunction-associated steatohepatitis (MASH), the gold standard test is the liver biopsy. A biopsy may not be necessary if other tests show evidence of MASH, but it can help determine the extent of your condition.

Your healthcare provider will collect a small sample of your liver tissue by inserting a needle through your abdomen into your liver. By analyzing the tissue, they’ll be able to tell how much fat and how much fibrosis your liver has.

How is metabolic dysfunction-associated steatohepatitis (MASH) treated?

Until recently, there were no medications that could treat MASH. But in March 2024, the FDA (U.S. Food and Drug Administration) approved the drug resmetirom (Rezdiffra™). Healthcare providers recommend using this medication in combination with nutritional changes and increased physical activity. Your provider can let you know if resmetirom is right for your situation.

Additional guidelines include:

• Losing weight. Losing 3% to 5% of your body weight has been shown to reduce fat levels in your liver. Losing between 5% and 10% of your body weight will help reduce inflammation as well. Your healthcare provider can help you create a plan to lose weight at a healthy pace.
• Managing your blood sugar. If you have diabetes, it’s especially important to monitor your blood sugar and take medications as directed. But it’s important for everyone with MASH to avoid sugar spikes from high-glycemic foods, such as sweetened products and white starches.
• Eating well. A balanced, heart-healthy diet is low in saturated fats and rich in monosaturated fats, such as those found in plants and seafood. It also includes plenty of fresh produce and whole grains. The Mediterranean diet is a good example.
• Regularly exercising. This will help you manage your weight as well as stress, which can affect liver health. Aim for 30 minutes of moderate exercise at least three times a week.

Home remedies include:

• Coffee. Some studies also suggest that drinking coffee daily can help prevent liver fibrosis due to metabolic dysfunction-associated steatohepatitis. You have to tolerate caffeine well, though — researchers say it takes more than two cups per day to work, and decaf doesn’t count.

How can I reduce my risk of metabolic dysfunction-associated steatohepatitis?

Manage your blood lipid levels by maintaining a weight, that’s healthy for you, reducing cholesterol in your diet and managing your blood sugar. Get a little exercise most days. Avoid carcinogens such as tobacco smoke.

Is metabolic dysfunction-associated steatohepatitis curable?

Lifestyle changes can absolutely reduce or eliminate the inflammation associated with steatohepatitis. Inflammation is what triggers fibrosis and progressive liver damage — it’s what separates those with metabolic dysfunction-associated steatohepatitis from those who live without problems from MASLD. Existing scar tissue can’t be revived, but most people have plenty of liver left to save.