Metabolic Dysfunction-Associated Steatotic Liver Disease

What is metabolic dysfunction-associated steatotic liver disease?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease. It’s the condition formerly known as nonalcoholic fatty liver disease (NAFLD), or just “fatty liver disease” for short. 

MASLD is a type of steatotic liver disease. This means it occurs when there’s the buildup of fat in liver cells. There are many causes of steatosis. These include heavy alcohol consumption, genetic conditions, and some medications. 

MASLD occurs in individuals without other known causes of steatosis who have at least one of the following risk factors:

• Body mass index (BMI) of 25 or higher (23 or higher in individuals of Asian descent)

• Larger waist size (over 31.5 inches in women, or 37 inches in men, although the cutoffs are slightly smaller for individuals of Asian descent)

• High blood pressure

• High fasting glucose or diabetes

• Abnormal cholesterol (high triglycerides or low high-density lipoprotein, known as HDL)

This condition can occur with or without liver inflammation. When there’s liver inflammation, this is an advanced stage of MASLD known as metabolic dysfunction-associated steatohepatitis (MASH). MASH was previously known as nonalcoholic steatohepatitis (NASH).

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What causes MASLD?

MASLD is caused by abnormal processing of fat by the liver. But researchers are unsure about the exact cause of this condition and why only some people develop it.

Certain conditions predispose individuals to MASLD. The risk factors linked with MASLD (listed in the section above) are part of a condition known as metabolic syndrome. 

Diet is also linked to MASLD. Eating a diet high in saturated fats — such as meat, dairy products, and coconut oil — increases the risk of MASLD. 

Genetics play a part in who develops MASLD and MASH as well. A family history of MASLD increases your risk.

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What are the symptoms of MASLD?

Most people with MASLD have no symptoms, especially in the early stages of the condition. But some people with MASLD may feel fatigue or pain in the upper right abdomen.

If MASLD progresses to MASH, the inflammation in the liver can eventually lead to liver cirrhosis. This is permanent scarring in the liver that affects liver function. 

Liver cirrhosis can cause the following symptoms:

• Jaundice (yellowing of the eyes or skin)

• Itching

• Ascites (fluid buildup in the abdomen)

• Leg swelling

• Confusion

• Nausea and vomiting

• Unintentional weight loss

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How do you diagnose MASLD?

The path to a MASLD diagnosis can start in a few different ways, but it often starts with abnormalities on testing that was performed for something else. For example, it may be diagnosed when someone gets imaging of their abdomen for another cause, and it shows steatosis (fat buildup) in the liver. Or it might get diagnosed when routine blood work shows abnormally elevated liver enzymes.

No matter how it starts, these abnormal findings typically lead to more testing to help diagnose MASLD:

• Blood tests: to assess your liver function and help to rule out other conditions that cause steatotic liver disease

• Imaging studies (usually an ultrasound): to check the appearance of your liver

• Transient elastography (FibroScan): to assess for liver scarring or fibrosis

• Liver biopsy: may be necessary if the diagnosis isn’t clear based on other testing

Other causes of steatotic liver disease should be ruled out before making a diagnosis of MASLD. These include:

• Heavy alcohol use

• Medications

• Genetic conditions, such as Wilson disease and alpha-1 antitrypsin deficiency

• Viral hepatitis

• Autoimmune hepatitis

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What is the treatment for MASLD?

MASLD is a reversible condition. The first step in treatment is usually lifestyle change, including:

• Weight loss: Even small reductions in weight make a difference. A 3% to 5% reduction in weight lowers liver fat. And 7% to 10% reduces liver inflammation.

• Healthy diet: Limit saturated fats (from meat, animal products, coconut oil), refined carbs (white bread, fries), and sugary drinks, which worsen liver fat buildup.

• Exercise: Moderate activity (30 to 60 minutes, several times per week) decreases fat in the liver, even without weight loss.

• Limiting alcohol use: It’s best to avoid it completely. But, if you drink, try to limit to no more than 1 drink per day for women or 2 for men.

Your provider may also recommend:

• Resmetirom: They may prescribe resmetirom if you have MASH and scarring (fibrosis) of your liver.

• Medications: These could include pioglitazone, semaglutide, or empagliflozin for diabetes or high BMI.

• Vitamin E: Vitamin E may help due to its antioxidant effects.

• Weight-loss surgery: This may be an option if lifestyle changes and medications aren’t enough.

• Treatment of other associated medical conditions: This could include treating conditions such as high blood pressure or high cholesterol.

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Risks and long-term complications of MASLD

When MASLD isn’t treated, it can lead to long-term health problems. The most serious include: 

• Liver cirrhosis: MASLD leads to inflammation in your liver. If this inflammation goes unchecked for a long period of time, it can cause permanent scarring (or fibrosis). This condition is called liver cirrhosis. Cirrhosis can’t be reversed and may progressively worsen, even with treatment. Sometimes, a liver transplant is required in the late stages.

• Hepatocellular carcinoma (HCC): This is a type of liver cancer. Individuals with cirrhosis are at highest risk of developing this cancer. If you develop cirrhosis, your healthcare team may recommend regular ultrasounds to screen for HCC.

• Heart disease: The same risk factors that increase the risk of MASLD also increase the risk of heart disease. These factors include high BMI, high cholesterol, and diabetes. So, individuals with MASLD have a high risk of developing heart disease and its associated complications. 

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How can you prevent MASLD?

MASLD is reversible — and also preventable — with lifestyle changes. These include:

• Maintaining a weight that’s healthy for your body

• Controlling or preventing diabetes

• Regular exercise

• Eating a balanced, nutritious diet 

• Treating contributing health conditions

• Limiting alcohol use

Don’t know where to start? Your primary care provider can help you focus on the most effective changes you can make to help prevent MASLD and its associated complications. Starting small and building up momentum are great strategies for making important lifestyle changes and taking control of your health.

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