Metabolic Dysfunction-associated Steatohepatitis (MASH) Overview

Metabolic dysfunction-associated steatohepatitis (MASH, formerly known as nonalcoholic steatohepatitis or NASH) is a type of fatty liver disease. It often develops due to a metabolic disorder, such as obesity or diabetes, resulting in a toxic buildup of fat in the liver. It is the most severe form of metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as nonalcoholic fatty liver disease or NAFLD).

MASH symptoms are often silent or nonspecific, making it difficult to diagnose. As a result, MASH patients can remain unaware of their condition until the late stages of the disease.

For most people, a buildup of fat in the liver, while not ideal, causes no problems. But in some people, the fat can become toxic to liver cells, causing inflammation and cell damage.

This article will discuss the symptoms, causes, diagnosis, and treatment of MASH.

Types of Fatty Liver Disease

The liver, the largest solid internal organ of the body, is responsible for making and storing energy, detoxifying drugs, and making bile, which helps carry away waste and aids in the digestion of fat in the small intestines. If the liver is injured, damaged, or stops functioning properly, fat may build up in the liver, causing fatty liver disease.

There are two main types:

• Metabolic dysfunction-associated steatotic liver disease (MASLD)
• Alcoholic fatty liver disease, also called alcoholic steatohepatitis (ASH)

MASH vs. MASLD vs. ASH

MASLD is a mostly benign condition characterized by fat accumulation in the liver. MASLD is sometimes called fatty liver disease because the presence of fat in the liver cells is the only characteristic of the condition.

MASLD has no symptoms of liver disease. It is quite common with up to 25% of people in the world having this condition.

MASH is a type of nonalcoholic fatty liver disease. About 20% of people with MASLD have MASH. MASH is commonly associated with obesity, type 2 diabetes, and high fat levels in the blood (hyperlipidemia).

Alcoholic steatohepatitis is associated with alcohol use disorder. If left untreated, both MASH and ASH patients can develop cirrhosis (hardening of the liver) and hepatocellular carcinoma (a type of liver cancer). But the likelihood of both is much higher in those with ASH—0.5% compared to 3% to 10%, respectively.

Symptoms

Oftentimes MASH presents with no symptoms, so you don’t even know you have it. If your MASH worsens, you may begin to experience symptoms that are indicative of the inflammation and damage done to your liver cells.

Common MASH symptoms include:

• Fatigue 
• Unexplained weight loss
• General weakness
• Discomfort in the upper right side of your belly

Causes

How non-fatty liver disease develops is still being studied. The first step involves insulin resistance and obesity, which results in high levels of fat infiltration into liver cells, called steatohepatitis.

Next is an inflammatory response that causes MASH. The mechanisms that set this off are still being researched. Inflammation can damage liver cells, causing fibrosis (scarring) of the liver.

Experts aren’t sure why some people get MASH and experience symptoms and others don’t. Researchers conclude that genetics, family history, and your environment all play a role.

People with the following conditions are at greater risk of developing liver disease and MASH symptoms:

• Obesity
• Insulin resistance and type 2 diabetes
• High cholesterol and high triglycerides
• Metabolic syndrome

MASH is typically seen in those who are 40 to 50 years old and have one or more of the problems listed above, although MASH can happen in people who have none of these risk factors.

Diagnosis

MASH may present with no symptoms, or the symptoms may go unnoticed, which makes this a hard condition to diagnose. Further still, there is no single test that can diagnose MASH.

To make a diagnosis, a healthcare professional will ask you about your medical history. This includes medications that you are taking, your symptoms, and the health problems you’ve had.

They will then perform a physical exam, looking specifically for signs of an enlarged liver or cirrhosis, like jaundice. 

If your medical history and physical exam point toward MASH, your doctor may suggest tests or imaging to see if fat is building up in your liver and to rule out other diseases. Blood tests include liver function tests and blood count tests.

Measuring liver function enzyme levels is especially important because they can help to diagnose MASH and differentiate MASH from alcoholic hepatitis. Levels of two liver enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are elevated in about 90% of people with MASH.

Imaging tests may include:

• Abdominal ultrasound
• Computed tomography (CT) scan
• Magnetic resonance imaging (MRI) scan

Your doctor may also do a liver biopsy to confirm MASH or rule out other causes of liver disease. In a liver biopsy, your doctor takes a sample of tissue from your liver and checks it for signs of MASH. A liver biopsy can also provide information on the extent of your MASH disease.

Treatment

In 2024, the Food and Drug Administration (FDA) approved Rezdiffra (resmetirom) for the treatment of adults with MASH with moderate to advanced liver scarring (fibrosis). Rezdiffra is the first and only FDA-approved treatment for MASH and should be used along with diet and exercise.

Ways to manage your underlying health conditions and leade a healthy lifestyle include:

• Reduce your total cholesterol level.
• Lose weight. If you are overweight or obese, losing 3% to 10% of your total body weight can reverse type 2 diabetes or insulin resistance in some people, although weight loss has positive health benefits in all people.
• Control diabetes. Maintaining a healthy blood sugar level via diet and medication decreases the likelihood of developing MASH symptoms.
• Avoid alcohol. Alcohol use is prohibited if you have MASH. Even a little alcohol can worsen damage to the liver, so stopping alcohol use altogether will give you the greatest health benefit. 
• Check your meds. Make sure that none of your medications, herbs, and supplements are toxic to the liver.
• Exercise regularly.
• Get vaccinated. Getting vaccinated for hepatitis A and B, the flu, and pneumococcal disease is essential. Not only are those with MASH more likely to get infections, but they are more likely to progress to cirrhosis or complete liver failure if they get hepatitis A or B.
• Supplement with vitamin E. If you do not have diabetes or heart disease, there is some evidence that taking vitamin E may slow down your rate of liver damage, but evidence is weak.

While these medications do not treat MASH directly, taking metformin and statins to treat associated metabolic conditions like insulin resistance and high cholesterol can help these associated conditions. If combined with weight loss and an improved diet, you can reverse fatty liver disease.

Two other drug options affirmed by the American Association for the Study of Liver Diseases for biopsy-proven MASH are vitamin E and pioglitazone (used to treat diabetes), but safety, efficacy, and side effect concerns linger. Never start one of these medications without a doctor’s supervision.

Prognosis 

Most people with MASH will not go on to develop serious liver problems. In fact, one study found that most people with MASH have a similar life expectancy to those without it, especially if their liver function tests are stable over time.

Life expectancy greatly decreases if MASH progresses to cirrhosis—complete scarring of the liver. It is the most serious complication of MASH.

The average life expectancy for those with decompensated liver failure is about two years. Estimates of progression to cirrhosis in MASH patients vary from 10% developing decompensated liver disease over 13 years to 25% developing cirrhosis over nine years.

Underlying conditions such as hypertension and type 2 diabetes may increase your risk of liver-related complications. But the worst outcomes for heart and liver disease are in those with metabolic syndrome—a combination of insulin resistance, obesity, and hyperlipidemia. Weight loss can decrease the risk of cirrhosis.

The prevalence of MASH has risen along with U.S. obesity rates. MASH is now a leading reason for liver transplants. For someone with cirrhosis, a liver transplant can add years to their life expectancy.

MASH patients without fibrosis are at a significantly lower risk of liver-related mortality compared to those with advanced fibrosis. Unlike alcoholic fatty liver disease, which is associated with liver-related causes of death, cardiovascular disease is often implicated as the cause of death in MASH cases without fibrosis.

Coping

Getting a diagnosis of MASH can be jarring, especially if you have underlying health conditions. It is natural for you to think that the last thing you need is another health complication, but MASH doesn’t always mean that you are in imminent danger.

Making the necessary lifestyle changes or continuing the changes you have already made often slows down the progression of the disease. Treating your underlying conditions will also help your MASH symptoms.

If you have been diagnosed with MASH, here are some important things you should do to avoid further liver damage:

• Limit or stop alcohol. There is no number of safe alcoholic drinks, so it’s probably best to avoid alcohol completely.
• Check your medications. Even generic drugs like acetaminophen, the generic ingredient in Tylenol and some cold medicines, may be harmful if you take too much for too long, especially if you have liver disease or drink alcohol heavily.
• Get vaccinated to protect against the liver viruses hepatitis A and B.
• Keep other health conditions under control.
• Get regular screening tests for liver cancer if you already have cirrhosis.

Summary

Metabolic dysfunction-associated steatohepatitis (MASH) is a form of fatty liver disease in which there is inflammation and destruction of liver cells. It may have no symptoms unless damage progresses. It is more often seen in people with obesity, metabolic syndrome, insulin resistance, or type 2 diabetes.

MASH can be diagnosed with blood tests and imaging. Treatment is with lifestyle measures and treating underlying conditions. The medication Rezdiffra can treat MASH when combined with diet and exercise. Prognosis is good unless it progresses to cirrhosis or liver cancer develops.

A Word From Verywell

MASH doesn’t have to dominate your life. Health complications are largely preventable if you work with a healthcare professional on a plan that is rooted in healthy behaviors. Remember to stop alcohol use and follow your vaccination regimen to avoid medical complications like cirrhosis or secondary infections.

Frequently Asked Questions

What’s the difference between MASH and MASLD?

MASLD is a condition when fat builds up in the liver. MASH is a subtype of MASLD that is characterized not only by fat infiltration in the liver, but also inflammation and liver cell damage. The two main types of MASLD are nonalcoholic fatty liver (NAFL) and metabolic dysfunction-associated steatohepatitis (MASH).

When does a fatty liver turn into cirrhosis?

Cirrhosis can take months or years to develop. While there are no definite estimates on the progression of fatty liver to cirrhosis, studies have shown that lifestyle changes and avoiding alcohol can decrease the likelihood of developing cirrhosis and long-term liver complications.

What can you do to reverse nonalcoholic cirrhosis of the liver?

There are no FDA-approved medications to reverse cirrhosis of the liver, but lifestyle changes such as healthy eating, regular exercise, and avoiding alcohol can decrease symptoms and the likelihood of developing portal hypertension and other liver-related complications.