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Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Overview
- What is MASLD and how common is it?
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition where there is a buildup of fat in the liver in people with diabetes, obesity, high blood pressure, or high cholesterol and drink little to no alcohol. Up to 30 out of 100 people or over 100 million of American adults have MASLD. Obesity is thought to be the most common cause of fatty infiltration of the liver. Some experts estimate that about two thirds of obese adults and half of obese children may have fatty liver. About 2 to 5 percent of adult Americans and up to 20 percent of those who are obese may suffer from the more severe condition metabolic dysfunction-associated steatohepatitis (MASH- the advanced stage of MASLD). The number of children who have MASH is not known.
Symptoms
- What are the symptoms of MASLD/MASH?
Many people with MASLD and MASH have no symptoms or findings on a doctor’s exam. Some patients may have abdominal discomfort and fatigue. Liver tests can be normal. We often find MASLD when a person is having abdominal imaging tests (ultrasound or CT scan) done for other reasons. Once cirrhosis occurs, patients may present with symptoms of liver failure, such as fluid buildup in legs or abdomen, liver confusion, or bleeding. Children may exhibit symptoms such as abdominal pain, which may be in the center or the right upper part of the abdomen, and sometimes fatigue. However, other causes of abdominal pain and fatigue should be considered. On physical examination the liver might be slightly enlarged, and some children may have patchy, dark discoloration of the skin present (acanthosis nigricans) most commonly over the neck and the under arm area.
Causes of MASLD/MASH
- What are the causes of MASLD/MASH?
MASLD is part of the metabolic syndrome characterized by diabetes, or pre-diabetes (insulin resistance), being overweight or obese, elevated blood lipids such as cholesterol and triglycerides, as well as high blood pressure. Not all patients have all the manifestations of metabolic syndrome. Less is known about what causes MASH to develop. Researchers are focusing on several factors that may contribute to the development of MASH. These include:
- Oxidative stress (imbalance between pro-oxidant and anti-oxidant chemicals that lead to liver cell damage)
- Production and release of toxic inflammatory proteins (cytokines) by the patient’s own inflammatory cells, liver cells, or fat cells
- Liver cell necrosis or death, called apoptosis
- Adipose tissue (fat tissue) inflammation and infiltration by white blood cells
- Gut microbiota (intestinal bacteria) which may play a role in liver inflammation.
Screening/Diagnosis
- Who should be screened for MASLD/MASH and how is it diagnosed?
People with risk factors for fatty liver are often overweight or obese, and can have diabetes, or high levels of triglycerides/cholesterol in their blood. People with these risk factors should have their liver tests checked at least once per year. Those who are found to have elevated liver tests or possible fat in their liver on an abdominal ultrasound, or other imaging study, should be evaluated for possible fatty liver in addition to other causes of elevated liver tests. Once fat is identified in the liver, other causes of liver fat such as drinking too much alcohol, certain medications, and other liver diseases must be checked for before making a diagnosis of fatty liver.
The next step is to determine whether the patient with fatty liver has only fat within their liver (also called steatosis), where scarring of the liver is rare or metabolic dysfunction-associated steatohepatitis (MASH) with both fat and inflammation in the liver that over time can cause scarring in the liver. The most accurate way to figure this out is to perform a liver biopsy, a procedure where a small needle is inserted through the skin after numbing medicine is given to obtain a small piece of the liver for examination under a microscope. A pathologist then interprets the biopsy sample and determines whether MASH is present and, if so, whether any liver damage or scarring has taken place. There are a growing number of alternatives to liver biopsy that can also provide much of the same information without requiring needle insertion into the liver. These include measuring liver stiffness and fat content of the liver with elastography testing through the use of a specialized ultrasound (Fibroscan®) or MRI scan. Special blood tests or a combination of routine blood tests can also be used to evaluate for possible liver scarring in patients with MASLD. Because none of these tests are perfect, patients with fatty liver are advised to discuss the risks and benefits of these tests with their doctor to decide which tests are best in their situation. In general, it is most beneficial to do a combination of tests to see if they all point to the same degree of fat in the liver and liver scarring. If the tests point to more significant scarring in the liver, your doctor may recommend a liver biopsy.
- Why should I be concerned about MASLD?
People with MASLD are at risk for heart disease and diabetes. In fact, heart disease is the number one cause of death among people with MASLD. About 20% of people with MASLD have liver inflammation called metabolic dysfunction-associated steatohepatitis (MASH), a more severe form of MASLD. About 20% of people with MASH may develop scar tissue called cirrhosis or end-stage liver disease. Cirrhosis occurs when the liver sustains substantial damage, and the liver cells are gradually replaced by scar tissue (see figure), which results in the inability of the liver to work properly. Some patients who develop cirrhosis may eventually require a liver transplant (surgery to remove the damaged liver and replace it with a “new” liver).
- How serious is my liver condition?
People with MASH or liver inflammation may have scar tissue, which causes liver tissue to stiffen up (rather than soft). Liver biopsy is not always necessary and non-invasive tests are now available to check for liver fat content and stiffness level. If the stiffness level is high, it can be either inflammation or scars or both and a liver biopsy can help to confirm how serious the condition is. If inflammation from MASH continues for years, an extensive amount of liver scar tissue can form which eventually leads to liver cirrhosis (severe scarring of the liver that can be permanent). Patients who develop cirrhosis related to MASH are at risk for two major developments: hepatocellular carcinoma (liver cancer) and/or end-stage liver disease. Developing either complication of cirrhosis significantly impacts life expectancy, but certain patients can be cured by undergoing a liver transplant if they are evaluated and found to be a good candidate. For this reason, patients with MASH cirrhosis should see a GI or liver specialist regularly who will monitor their liver function and screen them for liver cancer with periodic liver ultrasounds or other scans, in addition to monitoring for other complications.
Treatment of MASLD/MASH
- How is MASLD and MASH treated?
- Make lifestyle changes, including eating a healthy diet and exercise.
- Losing a total of 10% of your body weight may reduce fat and inflammation, and potentially regress scar tissue in your liver.
- Keep up the hard work because it is “REVERSIBLE!”
- Aim for small goals (lose 1-3 lbs per week) to make changes in habits over time and you will see a big difference in your health in the long term.
- There are currently no U.S. Food and Drug Administration (FDA) approved medications that can cure MASLD/MASH, but several promising medications are being studied.
- People with MASH may take vitamin E (particularly alpha-tocopherol) which may help reduce liver inflammation, but it is less helpful or less safe for people with diabetes or significant heart disease. Do not start this medication without talking with your liver doctor first.
- People with MASLD/MASH should limit alcohol and avoid it entirely if possible.
- It is very important to have diabetes, high blood pressure, and high cholesterol or lipids under control or within recommended guidelines.
- How should I change my diet?
- Various diets can lead to a reduction in liver fat, as long as there is a decrease in calories eaten in a day compared to a person’s daily required calories to maintain their current weight, with a goal of 500 fewer calories daily.
- Water is best. Avoid juice or sugary drinks.
- Avoid foods with added sugar including candy, desserts, and soda pop, especially high fructose corn syrup.
- Avoid highly processed snacks, fried foods, and fatty foods.
- Watch your portion size (how much food you choose to eat at one time). Use measuring cups to help control your portion.
- In a meal, fill half of your plate with fruits and vegetables, one quarter with a grain (like brown rice or whole wheat pasta), and one quarter with protein.
- Limit 1-2 healthy snacks during the day. Keep fruits and vegetables around for snacks.
- Try to eat at least 2.5 cups of fruit and vegetables every day.
- Try keeping a food log or diary, which may help to see how many calories you are eating.
- Meeting with a nutritionist or dietitian may be helpful for more information and to get personalized recommendations for healthy eating.
- How should I plan my exercise?
- No single program is best.
- Try to walk 10,000 steps a day.
- Aim for between 150 and 300 minutes of exercise per week.
- Find an activity that you enjoy and stick with it. Change it up and try new things, so you do not get bored over time.
- Find a partner to exercise with.
- Use activity trackers or app on your phone to track your activity.
Author(s) and Publication Date(s)
Ariel E. Feldstein, MD, and Marsha H. Kay, MD, FACG, Cleveland Clinic Foundation, Cleveland, OH – Published January 2006.
Naim Alkhouri, MD, and Marsha H. Kay, MD, FACG, The Cleveland Clinic, Cleveland, OH – Updated December 2012.
Neha Jakhete, MD, University of Maryland Medical System, Baltimore, MD, Arun Jesudian, MD, FACG, Weill Cornell Medicine, New York, NY, Paul Kwo, MD, FACG, Stanford Health Care, Stanford, CA – Updated 2020.
Alisa Likhitsup, MD, University of Michigan, Ann Arbor, MI – Updated March 2024.