Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Overview

What is MASH?

Metabolic dysfunction-associated steatohepatitis, commonly referred to as MASH, was previously named nonalcoholic steatohepatitis or NASH, but both terms refer to the same condition. The liver is an important organ that helps break down food, store energy, filter waste and remove toxins from the body. When fat deposits in the liver it is called steatosis.1 Although healthy livers contain some fat, if the liver has more than 5% fat, an individual has some form of metabolic dysfunction-associated steatotic liver disease (MASLD), which was previously known as nonalcoholic fatty liver disease (NAFLD).1, 2


MASLD is a condition in which fat builds up in the liver, and it tends to develop in those who are overweight and have diabetes, high cholesterol and/or high triglycerides. MASLD is more common in women and often has no symptoms. MASH is a progressive form of MASLD in which there is inflammation of the liver in addition to the buildup of excess fat. This inflammation can lead to scarring of the liver, which is also referred to as fibrosis. When the liver has had repeated scarring over years, it can progress to cirrhosis, liver failure and/or liver cancer. Cirrhosis is a result of liver damage in which the scarring over time has begun to interfere with the liver's ability to function. MASH is a leading cause of cirrhosis and liver transplant in the United States.1


Risk Factors for developing MASH include:3

  • Being overweight or obese
  • Having type 2 diabetes or insulin resistance
  • Having elevated levels of fats in the blood
    • High triglycerides
    • High cholesterol
    • Low HDL cholesterol or high LDL cholesterol
  • Having metabolic syndrome – a mix of conditions that consists of having 3 of the following:
    • Large waist size
    • High blood pressure
    • High blood sugar
    • High triglycerides
    • Low levels of good cholesterol in the blood (HDL)


It is unknown why some people with MASLD have simple fatty liver and others have MASH, but research suggests that genetics may play a role.2


In addition to the risk factors listed above, MASH is also more likely to occur in people who are older, are Hispanic or Asian, are post-menopausal women, or have obstructive sleep apnea. A few less-common factors are rapid excessive weight loss, infections like hepatitis C, exposure to certain toxins, polycystic ovarian syndrome, and taking certain medications such as glucocorticoids, synthetic estrogens, amiodarone, methotrexate or tamoxifen.3

How common is MASH?

MASLD is the most common chronic liver disease.P PAbout 25% of adults in the United States have MASLD, but less than 5% of people are aware of having the disease.1, 4

Most people with MASLD have simple fatty liver without the inflammation that characterizes MASH. It is estimated that only about 5% of adults in the United States have MASH.1

However, about 20% of those who already have MASLD will develop MASH over time. Of those who end up developing MASH, up to 25% may eventually have cirrhosis of the liver.1

5

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Symptoms

What are the symptoms of MASH?

MASLD and MASH rarely cause symptoms, which is why most people don’t even know they have these conditions. If symptoms do present, they typically include feeling more tired than usual or having pain or swelling in the upper right side of your abdomen, which is where your liver is located.1

Not everyone with MASH will progress to having cirrhosis, but if cirrhosis occurs, symptoms could
include:1

  • Itching
  • Swollen abdomen/stomach
  • Bruising and bleeding easily
  • Yellowing of the skin and eyes (often called jaundice)
  • Spider-like blood vessels just beneath the skin
  • A change in mental state such as behavior changes, slurred speech or confusion

How is it diagnosed?

Due to the lack of symptoms with MASLD or MASH, diagnosis is usually discovered during routine screening and blood tests. A physician may consider the following factors when diagnosing MASH:1

  • Medical history

    Doctors evaluate medications, alcohol use, diet, lifestyle and any other health conditions that increase risk of developing MASLD or MASH.

  • Physical examination

    Although not commonly seen, signs and symptoms of MASLD or MASH, such as yellowing of skin or eyes, checking for an enlarged liver and calculating a body mass index (BMI) may be observed.

  • Liver function tests (LFTs)

    Liver enzymes are proteins that help the liver perform its functions. LFTs measure liver enzyme levels through routine blood work. When liver damage occurs, it can cause these liver enzymes to leak out into the blood stream, which can lead to elevated levels that show up in blood work. Common LFTs are ALT (alanine aminotransferase) and AST (aspartate aminotransferase).

  • Fibrosis tests

    Fibrosis assessment tests are blood tests that help estimate the amount of scarring in the liver. Common fibrosis tests are AST-to-Platelet Ratio Index (APRI) score and Fibrosis-4 (Fib-4) score.

  • Imaging

    Ultrasound, CT scans and/or MRIs are noninvasive ways to determine the size of the liver in addition to the stiffness of the liver. Stiffness in the liver is another sign of scarring or fibrosis.

  • Liver biopsy

    MASH can be conclusively diagnosed by examining liver tissue with a microscope after getting a liver biopsy. After imaging studies and ruling out other potential causes, a liver biopsy may be done.

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Medications

The following specialty medications are available at Accredo, a specialty pharmacy, for MASH

NON-PHARMACOLOGIC MANAGEMENT

Lifestyle modifications are a primary prevention and treatment method for MASH. Diet, exercise and weight loss should be achieved alone and in addition to medication therapy with Rezdiffra. Lifestyle modifications consist of the following:1

  • Maintain a healthy weight
    • Losing at least 3% to 5% of total body weight can decrease fat deposits in the liver, while loss of 7% to 10% can reduce liver inflammation and scar tissue
  • Eat healthy fats and low sugar foods
    • The Mediterranean diet, which consists of vegetables, fruits, herbs, nuts and whole grains, is often recommended
  • Avoid fructose (found in sodas, juice, and processed foods)
  • Minimize alcohol intake
  • Increase exercise
    • Increasing physical activity by more than 60 minutes a week or maintaining more than 150 minutes a week of physical activity can provide a benefit.

2

  • 1

    Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2017;67(1):328-357. journals.lww.com

  • 2

    What is NASH? Fatty Liver Foundation. Accessed April 17, 2024. fattyliverfoundation.org

Medication Manufacturer
Rezdiffra™ (resmetirom) Madrigal Pharmaceuticals, Inc.

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Metabolic Dysfunction-Associated Steatohepatitis (MASH) Organizations

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