Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic dysfunction-associated steatotic liver disease is when too much fat builds up in your liver, affecting more than 30% of people worldwide. It is closely linked to conditions like obesity and type 2 diabetes, but with changes to diet and exercise, the damage can often be slowed or even reversed.

Table of contents

• What is metabolic dysfunction-associated steatotic liver disease?
• Other names for this condition
• What causes this disease and who is at risk?
• What are the symptoms?
• Possible complications
• How is the condition diagnosed?
• Treatment and management
• Outlook and prevention

What is metabolic dysfunction-associated steatotic liver disease?

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a group of liver diseases that happen when your body stores too much fat in your liver. Over time, this fat can cause inflammation (swelling and irritation) in your liver^[1].

It is one of the most common forms of chronic (long-term) liver disease. Experts estimate that it affects more than 30% of people worldwide and about 25 to 30% of the U.S. population^[1][10]. In fact, around one in three Australian adults has some form of fatty liver disease^[19].

MASLD develops when fat builds up in liver cells because of common conditions such as obesity (having a body mass index of 30 or higher), type 2 diabetes, high cholesterol, and high blood pressure^[5]. It is not caused by drinking alcohol^[4].

MASLD is more than just fat in the liver. It can progress to a more serious form of liver disease called metabolic dysfunction-associated steatohepatitis (MASH). About 13% of people with MASLD develop MASH, which involves fat deposits, swelling, and liver damage^[10][17].

• Liver

Other names for this condition

nonalcoholic fatty liver disease (NAFLD), fatty liver disease, steatotic liver disease

Until recently, MASLD was known as nonalcoholic fatty liver disease (NAFLD). The name changed because this form of liver disease has no link to alcohol, and after more study has been linked to metabolic dysfunction^[7]. The new term better reflects that the underlying cause of these disorders is linked to the presence of metabolic syndrome and metabolic risk factors, not just obesity^[4].

Similarly, the more serious form that was called nonalcoholic steatohepatitis (NASH) is now called metabolic dysfunction-associated steatohepatitis (MASH)^[3]. Patients seeking information about these conditions may see both the old and the new terms used. Even though the names have changed, the diseases are the same^[10].

What causes this disease and who is at risk?

You may develop MASLD if you have metabolic dysfunction, which is a group of conditions that affect your metabolism. Your metabolism is how your body changes food into energy^[1].

Conditions that may lead to MASLD include^[1]:

• Dyslipidemia: High levels of lipids, which are fatty or waxy substances that your body makes. Cholesterol is an example of a lipid in your blood.
• Obesity: When your body mass index is 30 or higher. People who carry extra weight in their belly have an increased risk of MASLD.
• Insulin resistance: When cells in your muscles, fat, and liver don’t respond to insulin as they should. Insulin is a hormone that manages blood glucose (sugar) levels.
• Type 2 diabetes: A chronic condition that happens when you have high blood sugar.

People with overweight or obesity are more likely to get MASLD and MASH. The risk is even higher in people with type 2 diabetes. Other risk factors include being 40 or older, smoking, high blood pressure, not moving around much, and a diet high in sugar and saturated fat^[17].

Researchers have also found several genetic variations that increase MASLD risk^[1]. Some people get MASLD and MASH despite having none of the above risk factors. Scientists are looking at whether genes may play a role^[17].

MASLD is the most common cause of chronic liver disease in children, affecting at least 10% of children in the United States^[7]. Lifestyle plays a prominent role in the development of MASLD. Epidemiological evidence suggests a close relationship with unhealthy lifestyles, including poor diet and physical inactivity^[11].

What are the symptoms?

MASLD develops over several years. You can have it without having symptoms. Many people with MASLD or MASH don’t feel sick at first^[1][17]. You may not notice changes in your body unless you develop MASH or complications like cirrhosis (severe scarring) or severe liver fibrosis (bands of scar tissue in your liver)^[1].

Eventually, MASLD may cause symptoms such as^[17]:

• Fatigue and extreme weakness
• An ache in your upper right abdomen, where your liver is
• General weakness
• Loss of appetite

MASLD that progresses to MASH may cause symptoms such as^[17]:

• Swollen belly, legs, or feet
• Unexpected weight loss
• Yellowing of your skin and eyes (called scleral icterus or jaundice)
• Itchy skin
• Trouble breathing
• Easy bruising and bleeding
• Enlarged spleen
• Spider-like blood vessels beneath the skin

Possible complications

Some people with MASLD may develop MASH. The condition can lead to more serious forms of disease, including^[1]:

• MASH with liver fibrosis: Fibrosis is bands of scar tissue in your liver. Fibrosis happens when your liver tries to repair and replace damaged cells.
• MASH-related cirrhosis: This is scarring that damages your liver.
• Hepatocellular carcinoma: This is a type of liver cancer that can be caused by MASH.

Cirrhosis, with its extensive scarring and damage, is much more difficult to reverse. Having cirrhosis increases the risk of liver failure or liver cancer, which may result in the need for a life-saving liver transplant^[10].

MASLD may also increase your risk of developing serious conditions like^[1]:

• Cancer, including breast cancer and colorectal (colon) cancer
• Cardiovascular disease
• Diabetes in people who don’t already have diabetes

The leading causes of death in people with fatty liver disease are cardiovascular disease and cancers^[19].

How is the condition diagnosed?

Since MASLD and MASH don’t always cause symptoms, screening (checking for a disease despite the absence of symptoms) is critical. Catching either condition early makes treatment more effective and can prevent further damage to your liver^[17].

Getting a diagnosis of fatty liver disease can come as a shock. You may have had no symptoms and perhaps received your diagnosis after an ultrasound for a completely different matter^[19].

If you are at high risk for MASLD or MASH, your healthcare professional may recommend screening. This may include^[17]:

• Blood tests to look for increased levels of liver enzymes or signs of liver damage
• Imaging studies to look for increased fat in the liver or signs of swelling, inflammation, or scarring

To diagnose MASLD or MASH, your healthcare professional will review your medical history and perform a physical exam. They may also order blood tests and imaging studies. Although noninvasive diagnostic tests are usually sufficient, liver biopsy (removing a small piece of tissue for testing) remains the gold standard. Differentiating MASLD from MASH is difficult without a liver biopsy, and elevated liver enzymes are not a sensitive predictor for identifying MASH^[4].

Treatment and management

Lifestyle modification is the cornerstone of MASLD management. The main treatment is eating a well-balanced diet, being physically active, and (if needed) losing weight. Research shows these can reduce liver fat and in some cases reverse MASLD^[3].

The good news about MASLD is that it can get better and even be completely reversible through changes in eating habits and exercise, and the weight loss resulting from these changes^[10]. Early diagnosis and treatment can keep MASLD from getting worse^[1].

Weight loss and lifestyle changes

For most people, weight loss is the main treatment for MASLD. For people with obesity or those who are overweight, weight loss has been shown to improve MASLD and its symptoms, as well as overall quality of life. Research shows that losing 7% to 10% of total body weight can reduce liver inflammation and in some cases reverse MASLD^[13].

Weight loss of 7–10% is central to lifestyle management; however, liver and cardiometabolic benefits are attainable with improved diet quality and exercise even without weight loss^[18].

Diet

A healthy, balanced diet that is low in processed foods and sugar including fructose (fruit sugar) can help reduce fat in the liver. An example is the Mediterranean Diet, which consists of lots of vegetables, fruit, unprocessed cereals, legumes, olive oil, and nuts and seeds; moderate quantities of fish, seafood, eggs, cheese, yoghurt, and poultry; and minimal amounts of red meat, processed meats (like salami and ham), and sweets^[19].

Dietary management emphasises energy deficit and improved diet quality, especially the Mediterranean diet, although sociocultural adaptations to meet preferences should be considered^[18].

Physical activity

Increasing physical activity and reducing sedentary behavior can prevent MASLD, with strongest evidence supporting regular structured moderate–vigorous aerobic exercise for 150–240 minutes per week. Resistance training (strength training) in addition to aerobic exercise should be considered and prioritised for those who are losing body mass via diet and pharmacological approaches and those with sarcopenia (muscle loss), to minimise bone and lean mass loss^[18].

Other lifestyle factors

Lifestyle intervention for MASLD should consider an integrated 24-hour approach that is cognisant of diet, physical activity and exercise, sedentary behavior, smoking, alcohol intake, and sleep. Limited evidence suggests that sleep is important for MASLD prevention^[18].

Medication

In Europe, there is no approved drug for MASLD to date and there is a substantial unmet medical need for effective treatments for patients with MASLD^[11]. However, the U.S. Food and Drug Administration recently approved a medication called resmetirom for patients with MASH and moderate to severe fibrosis. This is the first medication to specifically treat MASH and fibrosis^[10]. In selected patients with stage F2 to F3 (moderate to severe) fibrosis, resmetirom can be used^[4].

There are more than 50 active clinical trials targeting metabolic factors and inflammatory and fibrogenic pathways at the time of research. Until new drugs are approved, all the efforts in clinical practice must focus on lifestyle correction^[11].

Surgery

Timely consideration of bariatric surgeries should be given to patients with MASLD who meet the criteria for such interventions^[8].

Outlook and prevention

Life expectancy varies depending on whether you have MASLD or MASH. Factors such as scarring and other health conditions also affect how long you can live with MASLD or MASH^[5].

Without treatment, MASLD can cause more serious liver diseases. Once MASLD progresses to end-stage liver disease, treatment efficacy becomes limited and may require liver transplantation^[1][8]. Today, fatty liver disease is the number one reason Australians need a liver transplant^[19].

Having fatty liver is like a canary in the coal mine. It’s an early warning sign that a person is at risk of future health problems like diabetes or heart disease^[19].

MASLD is considered the hepatic (liver-related) manifestation of the metabolic syndrome, with lifestyle playing a fundamental role in its development. Diet change and physical activity are the cornerstones of treatment, encompassing weight loss and healthier behaviours and a holistic approach^[11].

Losing weight and becoming more active may slow down or reverse liver damage from MASLD^[1]. A healthy lifestyle can effectively promote the reduction of fatty liver grade in patients with MASLD, demonstrating positive effects in improving lipid metabolism and inflammatory responses^[16].