Metabolic Dysfunction-Associated Steatohepatitis

Metabolic dysfunction-associated steatohepatitis is a serious liver disease that develops when too much fat builds up in the liver, causing inflammation and damage. Often called a “silent disease,” it can progress without obvious symptoms for years, potentially leading to severe scarring, liver failure, or liver cancer.

Table of contents

• What is metabolic dysfunction-associated steatohepatitis?
• Symptoms
• Causes and risk factors
• Complications
• Diagnosis
• Treatment
• Related conditions

MASH, nonalcoholic steatohepatitis, NASH, metabolic dysfunction associated steatohepatitis

What is metabolic dysfunction-associated steatohepatitis?

Metabolic dysfunction-associated steatohepatitis (MASH) is a serious liver disease that develops when fat buildup in your liver causes inflammation and cell damage^[1]. This condition was previously known as nonalcoholic steatohepatitis (NASH) before being renamed in 2023 to better reflect its connection to metabolic health problems^[1][5].

MASH is part of a broader group of liver diseases called MASLD, which stands for metabolic dysfunction-associated steatotic liver disease^[1]. Unlike simple fatty liver, where fat accumulates without causing much harm, MASH involves active inflammation and damage to liver cells^[4]. The word steatohepatitis combines “steato” (meaning fat) and “hepatitis” (meaning liver inflammation).

MASH develops in people who drink little or no alcohol, which is why it was originally called “nonalcoholic” steatohepatitis^[4]. It is most strongly linked to conditions like obesity, type 2 diabetes, and problems with how your body processes sugar and fat^[1].

About 20% of people who have fatty liver disease progress to develop MASH^[7]. While MASH can sometimes stay stable or even improve with lifestyle changes, it can also worsen over time^[4]. Without treatment, MASH can lead to serious complications including cirrhosis (severe scarring of the liver), liver cancer, or liver failure^[1].

Symptoms

You may not have symptoms of MASH until it severely damages your liver^[1]. The condition develops slowly over the years, which is why MASH is often called a “silent disease”^[1][19]. Many people only discover they have MASH during routine checkups or tests done for other reasons^[1].

When symptoms do appear, they may include^[1]:

• Fatigue
• Discomfort or pain in your upper right belly (where your liver is located)
• Unexplained weight loss
• Muscle weakness or muscle loss
• Swollen belly or legs
• Yellowish tint to your eyes and skin (jaundice) as the condition worsens

Because early MASH often has no obvious symptoms, it’s important to get regular checkups, especially if you have risk factors like obesity, diabetes, or high cholesterol^[1]. When present, symptoms of MASH are often non-specific and may be incorrectly attributed to other health conditions you might have^[19].

Causes and risk factors

MASH happens when too much fat builds up in the liver and causes inflammation^[1]. This is often linked to problems with how your body processes sugar and fat^[1]. The condition is strongly connected to a cluster of health problems called metabolic dysfunction^[2].

Common risk factors and causes include^[1]:

• Obesity or being overweight
• Type 2 diabetes
• High cholesterol
• High triglycerides (a type of fat in your blood)
• High blood pressure
• Insulin resistance (when your body’s cells don’t respond properly to insulin, a hormone that manages blood sugar)

You may develop MASH even if you don’t have overweight, but you have issues like high cholesterol or high blood pressure^[1]. Researchers have also found that certain genetic variations may increase your risk of developing MASLD and MASH^[2][7].

The condition is becoming more common, especially in Western and Middle Eastern nations, as the number of people with obesity rises^[5]. MASH can affect people of any age, including children, though it is more common in people aged 40 or older^[16].

Complications

Without treatment, MASH can cause serious and potentially life-threatening complications^[1]. The inflammation and cell damage in MASH can lead to progressive scarring of the liver over time.

Major complications include^[1]:

• Liver fibrosis: Scarring in your liver that gets worse over time and can lead to cirrhosis. Fibrosis happens when your liver tries to repair and replace damaged cells^[2].
• Cirrhosis: Severe scarring that affects how your liver works. This is often permanent^[1].
• Liver failure: When the liver can no longer function properly. Liver failure may happen suddenly and requires immediate medical treatment or a liver transplant^[1].
• Hepatocellular carcinoma: MASH increases your risk of this common type of liver cancer^[1][2].
• Heart disease: The condition increases your risk of heart attack, stroke, and other cardiovascular conditions. In fact, cardiovascular disease is the leading cause of death in people with MASH^[1][6].

MASH progression is often slow, but some people may experience rapid progression from no fibrosis to advanced fibrosis in approximately six years^[19]. MASLD and MASH may also increase your risk of other cancers, including breast cancer and colorectal cancer^[2].

Diagnosis

Diagnosing MASH involves several steps because it doesn’t cause symptoms right away^[1]. A healthcare provider will do a physical exam and ask if you have any conditions that increase your risk of developing MASH^[1].

Blood tests

Your provider will do blood tests to look for damage or inflammation in your liver^[1]. Tests may include^[1]:

• CBC (complete blood count)
• BMP (basic metabolic panel)
• Lipid panel (cholesterol and triglyceride levels)
• Hemoglobin A1C (to check blood sugar control)

Imaging tests

These tests provide images of your liver’s inside. Your provider will look for changes in your liver that could be signs of MASH^[1]. Imaging tests may include^[1]:

• CT scan (computed tomography scan)
• Ultrasound
• FibroScan®, a type of liver elastography
• Magnetic resonance elastography and proton density fat fraction (MRE-PDFF), which measures fat in your liver

Liver biopsy

Your provider may do a liver biopsy to get a small sample of your liver^[1]. A medical pathologist will examine the sample under a microscope to look for inflammation, fat accumulation, and scarring. While liver biopsy has traditionally been the standard way to diagnose MASH, there is greater acceptance of noninvasive tests to screen for and diagnose the condition^[19].

Treatment

The main treatment for MASH is lifestyle modification, including eating a well-balanced diet, being physically active, and losing weight if needed^[5][14]. Lifestyle changes are the cornerstone of MASH management and can help manage related metabolic conditions^[6][8].

Weight loss

For most people with MASH, weight loss is the main treatment^[14]. Losing 7% to 10% of total body weight can reduce liver fat and inflammation and may even reverse MASH^[14]. Research shows that weight loss can improve MASH and its symptoms, as well as overall quality of life^[14].

Diet

Dietary management emphasizes reducing calories and improving diet quality^[17]. The Mediterranean diet has the strongest evidence for helping people with MASH, although you may need to adapt it to meet your cultural preferences^[17]. Eating a well-balanced diet can treat and in some cases reverse fatty liver disease^[21].

Physical activity

Increasing physical activity and reducing sedentary behavior can help prevent MASLD^[17]. The strongest evidence supports regular structured moderate to vigorous aerobic exercise for 150 to 240 minutes per week^[17]. Resistance training (strength training) in addition to aerobic exercise should also be considered, especially for those losing body weight or those with muscle loss^[17].

Even without weight loss, liver and heart-related health benefits can be achieved with improved diet quality and exercise^[17].

Medications

In 2024, the U.S. Food and Drug Administration approved the first medication specifically for treating MASH with fibrosis^[12]. The medication, called resmetirom, has shown promise in treating the more severe type of MASLD^[12]. Other medications are being studied in clinical trials^[10][13].

Your healthcare provider may also prescribe medications to manage related conditions like diabetes, high cholesterol, or high blood pressure. It’s important to work closely with your healthcare team to develop a treatment plan that’s right for you.

Surgery

For people with severe obesity, bariatric surgery (weight loss surgery) may be considered^[8]. This type of surgery can lead to significant weight loss and may improve MASH.

Related conditions

MASH is closely linked with several other health conditions. There is significant overlap between MASH and other metabolic diseases^[19].

Related conditions include:

• Obesity
• Type 2 diabetes
• High cholesterol
• High blood pressure
• Insulin resistance
• Cardiovascular disease
• Liver cirrhosis
• Liver cancer
• Liver failure

MASH is now considered the liver manifestation of metabolic syndrome^[19]. Many people with MASH have multiple metabolic health problems that need to be managed together.