Patient education: Metabolic dysfunction-associated steatotic liver disease (Beyond the Basics)

INTRODUCTION — Metabolic dysfunction-associated steatotic liver disease, or "MASLD," is a condition in which fat builds up in the liver due to metabolic stress from excess weight, high blood sugar, high cholesterol, or high blood pressure (figure 1). MASLD used to be called "nonalcoholic fatty liver disease" (NAFLD).

When the liver is steatotic (has fat buildup) and is inflamed, the condition is called "metabolic dysfunction-associated steatohepatitis" or "MASH." MASH used to be called "nonalcoholic steatohepatitis" (NASH). The information in this article is mostly about MASH, as this is the condition that can lead to the most problems.

Alcohol use disorder and other conditions can also lead to liver problems. A person can have liver injury from more than one cause. When a person has steatotic liver from both metabolic stress and alcohol, it is called MetALD.

CAUSES OF MASH — The cause of MASH is metabolic dysfunction seen in people with certain medical conditions such as insulin resistance (prediabetes or diabetes), high blood pressure, high cholesterol, and/or obesity. This combination of disorders is often called "metabolic syndrome."

●Overweight or obesity – Most people with MASH have excess body weight or obesity.

●Hyperlipidemia – Some people with MASH have hyperlipidemia (high blood triglyceride levels and/or high blood cholesterol levels). (See "Patient education: High cholesterol and lipids (Beyond the Basics)".)

●Insulin resistance – Insulin resistance refers to a state in which the body does not respond adequately to insulin. People with insulin resistance have prediabetes or type 2 diabetes. Normally, sugar gets into the cells with the help of a hormone called insulin, which is made in the pancreas. In people with insulin resistance (prediabetes or type 2 diabetes), the body stops responding to normal or high levels of insulin, which causes sugar to build up in the blood; eventually, the pancreas becomes unable to produce enough insulin (see "Patient education: Type 2 diabetes: Overview (Beyond the Basics)"). This often occurs in people with hyperlipidemia who have obesity. This group of symptoms is known as the metabolic syndrome, and it is frequently seen in people with MASH. (See "Patient education: Type 2 diabetes: Overview (Beyond the Basics)".)

SYMPTOMS — Most people with MASH have no symptoms. Sometimes, people have vague symptoms like fatigue, a general feeling of being unwell, and discomfort in their upper right abdomen.

DIAGNOSIS — MASH may be discovered following routine blood tests. Additional tests help confirm the presence of MASH and rule out other types of liver disease. Imaging tests (such as ultrasound or magnetic resonance imaging [MRI]) may reveal fat accumulation in the liver but cannot differentiate MASH from other causes of liver disease that have a similar appearance. A liver biopsy may be required to confirm MASH if other causes of liver disease cannot be excluded.

Liver function tests — Blood tests for liver function measure levels of substances produced or metabolized by the liver. These levels can help to diagnose MASH. Levels of two liver enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are elevated in most people with MASH. In some people, another liver enzyme, alkaline phosphatase, can be elevated.

Other blood tests — Additional blood tests are useful for ruling out other causes of liver disease. These usually include tests for viral hepatitis (hepatitis B or C) and may include tests for less common causes of liver disease. (See "Patient education: Hepatitis B (Beyond the Basics)" and "Patient education: Hepatitis C (Beyond the Basics)".)

Liver biopsy and transient elastography — Although other tests may suggest a diagnosis of MASH, sometimes a liver biopsy is required to confirm it. A liver biopsy may be needed if other causes of liver disease cannot be ruled out with standard blood and imaging tests. A liver biopsy can also help determine the severity of inflammation, detect liver scarring (called "fibrosis" or, in severe cases, "cirrhosis"), and may provide clues about the future course of the condition. The procedure involves collecting a small sample of liver tissue, which is sent to a laboratory for microscopic examination and biochemical testing. More detailed information about liver biopsies is available in a separate topic review. (See "Patient education: Liver biopsy (Beyond the Basics)".)

Transient elastography is a noninvasive test that can use ultrasound to determine how "stiff" the liver is. This stiffness can then be used to estimate how much scarring there is in the liver and to determine if cirrhosis has developed.

TREATMENT — Treatment of MASH focuses on weight loss, controlling some of the medical conditions associated with MASH (such as diabetes and obesity), and monitoring for progression.

General measures — General treatment measures include:

●Vaccines – Your doctor might recommend getting vaccines to protect against hepatitis A and B. These are infections that can harm your liver. Depending on which vaccines you have had in the past, you may need others, too.

●Lipid-lowering therapy – If you have high lipids or cholesterol, it's important to get treatment. (See "Patient education: High cholesterol and lipid treatment options (Beyond the Basics)".)

●Avoiding alcohol – Alcohol can make liver problems worse.

Weight loss — Losing weight can help to reverse MASH and improve the metabolic dysfunction. Weight loss should be gradual (for example, 1 to 2 lbs per week) since rapid weight loss has been associated with worsening of liver disease. A health care provider or nutritionist can provide an individualized weight loss plan. (See "Patient education: Losing weight (Beyond the Basics)".)

People with MASH and obesity who undergo bariatric (weight loss) surgery often have improvement of their liver disorder. (See "Patient education: Weight loss surgery and procedures (Beyond the Basics)".)

Treatment of insulin resistance — Several drugs are available for people with insulin resistance, and they are being studied in people with MASH.

More information about treatments for insulin resistance is available separately. (See "Patient education: Type 2 diabetes: Treatment (Beyond the Basics)", section on 'Thiazolidinediones'.)

Vitamin E — For people with severe forms of MASH who do not have diabetes, health care providers sometimes recommend supplements of vitamin E. There is some evidence that vitamin E might reduce some of the liver damage that occurs as part of MASH, but the evidence is weak, and there is also evidence that high-doses of vitamin E supplements increase the risk of death. Do not take vitamin E unless your health care provider recommends it.

Other drug therapies — For people with MASH and liver fibrosis who do not lose weight, another treatment option is a medication called resmetirom. Studies on the effects of resmetirom are ongoing.

PROGNOSIS — MASH is typically a chronic, life-long condition. It is difficult to predict the progression of MASH in an individual, but weight loss can significantly improve or reverse MASH. Other factors have been useful in predicting the course of this condition such as features in the liver biopsy.

The good news is many people with metabolic dysfunction-associated steatotic liver disease, (MASLD) will not develop serious liver problems. One study showed that most people with MASLD live as long as those without it.

However, in some people, MASH gets worse over time. The most serious complication of MASH is cirrhosis, which is when the liver becomes severely scarred. Cirrhosis does not always cause symptoms, but when symptoms do occur, they can include swelling in the legs, trouble breathing, or fatigue. Older people with diabetes may be at increased risk for developing cirrhosis. (See "Patient education: Cirrhosis (Beyond the Basics)".)

People with MASH often have metabolic syndrome (insulin resistance, obesity, and hyperlipidemia) (see 'Causes of MASH' above). Metabolic syndrome puts you at increased risk for heart disease. The good news is that the treatments for MASH (particularly weight loss) also help treat the other problems that are part of the metabolic syndrome.

WHERE TO GET MORE INFORMATION — Your health care provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for health care professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Metabolic dysfunction-associated steatotic liver disease (The Basics)
Patient education: Cirrhosis (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Type 2 diabetes: Overview (Beyond the Basics)
Patient education: High cholesterol and lipids (Beyond the Basics)
Patient education: Hepatitis A (Beyond the Basics)
Patient education: Hepatitis B (Beyond the Basics)
Patient education: Hepatitis C (Beyond the Basics)
Patient education: Liver biopsy (Beyond the Basics)
Patient education: Losing weight (Beyond the Basics)
Patient education: Type 2 diabetes: Treatment (Beyond the Basics)
Patient education: Cirrhosis (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Immunizations for adults with chronic liver disease
Management of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults
Pathogenesis of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease)
Clinical features and diagnosis of metabolic dysfunction-associated steatotic liver disease (nonalcoholic fatty liver disease) in adults
Noninvasive assessment of hepatic fibrosis: Overview of serologic tests and imaging examinations

The following organizations also provide reliable health information.

●National Library of Medicine

     (www.nlm.nih.gov/medlineplus/healthtopics.html)

●National Institute of Diabetes and Digestive and Kidney Diseases

     (www.niddk.nih.gov)

●The American Association for the Study of Liver Diseases

     (www.aasld.org)

●The American Liver Foundation

     (www.liverfoundation.org)