Liver Disease

What Is Metabolic Dysfunction–Associated Steatohepatitis?

Ashley Welch
By
Ira Daniel Breite, MD
by
Published on April 19, 2024

Metabolic dysfunction–associated steatohepatitis (MASH) is a progressive form of liver disease that occurs when there’s an accumulation of fat in the liver.

MASH is the most severe stage of metabolic dysfunction–associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease.

Doctors don’t fully understand why some people with MASLD develop MASH and some don’t. However, MASLD and MASH are more common in people who have certain conditions associated with high blood lipid (fat) levels, such those with type 2 diabetes and obesity.

While it’s normal for the liver to store some fat, if more than 5 to 10 percent of the organ’s weight is fat, it’s called steatosis, or fatty liver.

 For most people, steatosis does not cause any issues, but for others the fat can cause inflammation and damage to the liver.
An estimated 24 percent of adults in the United States have MASLD, while 1.5 to 6.5 percent have MASH. In other words, abnormal liver enzymes and MASLD are very common but don’t often lead to MASH.

Risk Factors for MASLD and MASH

While chronic alcohol use or viruses like hepatitis B and hepatitis C commonly cause liver disease, people with MASLD or MASH have neither virus nor do they drink excessively. It’s not fully understood why MASLD and MASH occur, but high levels of fat in the blood appear to be a big culprit. However, not everyone with MASLD or MASH fits this profile.

Still, there are risk factors that make a person more likely to have these conditions:

  • Obesity Studies have found that having a body mass index (BMI) of 30 to 32.5 (obese) was associated with a five- to ninefold higher risk of MASLD and MASH, while a BMI of 37.5 to 40 (severely obese) was associated with a ten- to fourteenfold higher risk compared with normal weight individuals.

  • Type 2 Diabetes Research estimates that up to 75 percent of people with type 2 diabetes have MASLD. When a person has both of these conditions, they are more likely to advance to MASH at an accelerated rate.

  • Abnormal Levels of Fat in the Blood High levels of triglycerides, high levels of LDL (“bad”) cholesterol, and low levels of HDL (“good”) cholesterol are associated with MASH.

  • Metabolic Syndrome Conditions linked to obesity, including high blood pressure, high triglycerides, high blood sugar, and a large waist size, are risk factors for MASH.

Other risk factors associated with MASH include being over 40 years old and being postmenopausal.

What Are the Symptoms of MASH?

Many people don’t experience symptoms of MASH, particularly in the early stages. If symptoms do appear, it may be during the moderate stage and include the following:

  • Ache in the upper right area of the abdomen (where the liver is)
  • Fatigue and weakness
  • Loss of appetite
  • Unexplained weight loss
As MASH progresses, cirrhosis, or scarring of the liver, can develop. Symptoms include the following:

  • Jaundice, or yellowing of the skin and whites of the eyes
  • Bruising and bleeding easily
  • Swelling of the abdomen
  • Swelling of the legs and feet
  • Enlarged liver or spleen
  • Enlarged veins in your esophagus, which can bleed
  • Portal hypertension, which can cause intestinal bleeding
  • Shortness of breath
  • Persistent itchy skin
  • Confusion, drowsiness, and slurred speech (hepatic encephalopathy)
  • Spiderlike blood vessels beneath the surface of the skin

Metabolic Dysfunction–Associated Steatohepatitis Diagnosis

If your doctor suspects that you have liver disease, they’ll run a series of tests that can identify liver damage. To diagnose MASLD or MASH, tests can include the following:

  • Blood Tests Taking a blood sample can help detect evidence of liver inflammation, including elevated liver enzymes. A lipid panel will tell your doctor if you have elevated levels of fat in your blood, while a fibrosis assessment test can help identify fibrosis, or scarring. Additional blood tests may rule out other conditions. Most people find out that they have liver disease when routine blood tests detect an issue, and more tests are ordered.
  • Imaging Tests An abdominal ultrasound, CT scan, or MRI will allow your doctor to look at your liver and check for signs of inflammation, swelling, and scarring.
  • Liver Stiffness Tests These modified imaging tests measure stiffness and fibrosis levels in your liver. They include FibroScan and magnetic resonance elastography, which combines ultrasound and MRI imaging.
  • Liver Biopsy The gold standard test to confirm a MASH diagnosis is a liver biopsy, although it’s usually not needed if your doctor is able to find evidence of MASH through other testing measures. To perform a biopsy, your doctor will insert a small needle through your abdomen to collect a tissue sample from your liver. This sample can then be analyzed to identify the amount of fat in the liver and determine if there is scarring.

Metabolic Dysfunction–Associated Steatohepatitis Treatment

In March 2024, the U.S. Food and Drug Administration (FDA) approved resmetirom (Rezdiffra) for the treatment of MASH. This is the first and only medication approved to treat this disease.

A clinical trial published in February 2024 in The New England Journal of Medicine followed nearly a thousand participants with MASH over the course of a year. The researchers found that those who were treated with resmetirom experienced less disease progression and more improvement in liver fibrosis compared with those receiving a placebo.

Though not approved by the FDA as a treatment for MASH, semaglutide (Ozempic, Rybelsus), a weight loss and diabetes drug, has shown some evidence of helping to manage the liver condition.

Most people will not need to take medication for MASH. However, a healthy lifestyle, especially managing your weight, can be very beneficial. Studies have shown that losing 7 to 10 percent of your body weight was associated with significant reductions in liver fat.

 However, even losing 3 to 5 percent can start to make a difference.

Other important lifestyle changes to help protect your liver include these recommendations:

  • Eat a balanced, heart-healthy diet like the Mediterranean diet.
  • Get regular exercise.
  • Manage your blood sugar.
  • Reduce cholesterol in your diet.
  • Avoid carcinogens such as tobacco smoke.
  • Drinking more than two cups of coffee a day can help prevent liver fibrosis due to MASH, according to some studies.

If MASH has progressed to cirrhosis of the liver, a liver transplant may be needed.

Metabolic Dysfunction–Associated Steatohepatitis Life Expectancy

Research has found that MASLD reduces life expectancy by four years.

If MASLD progresses to MASH and ultimately advances to cirrhosis of the liver, life expectancy can vary widely, depending on how advanced the cirrhosis is, complications, treatment, and your overall health. In the early stages of cirrhosis, life expectancy may still be more than 15 years, but those with decompensated cirrhosis (when liver function decreases to the point of liver failure) have an average life expectancy of seven years. In severe cases, some people have less than two years.

Metabolic Dysfunction–Associated Steatohepatitis Complications

The main complication of MASH is fibrosis. Over time, this scarring can lead to cirrhosis, or the replacement of healthy liver tissue with scar tissue.

Cirrhosis of the liver is associated with an increased risk of the following:

  • Liver cancer
  • Cardiovascular disease
  • Type 2 diabetes
  • End-stage liver failure

Editorial Sources and Fact-Checking

Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.

Sources

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  2. Nonalcoholic Fatty Liver Disease (NAFLD). American Liver Foundation. March 7, 2024.
  3. Definition & Facts of NAFLD & NASH. National Institute of Diabetes and Digestive and Kidney Diseases. April 2021.
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  5. Ciardullo S et al. Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes: Screening, Diagnosis, and Treatment. Journal of Clinical Medicine. September 2023.
  6. NASH Causes & Risk Factors. American Liver Foundation. January 18, 2024.
  7. Nonalcoholic Fatty Liver Disease. Mayo Clinic. April 4, 2024.
  8. FDA Approves First Treatment for Patients With Liver Scarring Due to Fatty Liver Disease. U.S. Food and Drug Administration. March 14, 2024.
  9. Harrison S et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH With Liver Fibrosis. The New England Journal of Medicine. February 2024.
  10. Newsome P et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. The New England Journal of Medicine. November 2020.
  11. Alam S et al. Effect of Weight Reduction on Histological Activity and Fibrosis of Lean Nonalcoholic Steatohepatitis Patient. Journal of Translational Internal Medicine. September 2019.
  12. Wadhawan M et al. Coffee and Liver Disease. Journal of Clinical and Experimental Hepatology. March 2016.
  13. Battistella S et al. Liver Transplantation for Non-Alcoholic Fatty Liver Disease: Indications and Post-Transplant Management. Clinical and Molecular Hepatology. February 2023.
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