Metabolic dysfunction–associated steatotic liver disease

Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is a type of chronic liver disease. This condition is diagnosed when there is excessive fat build-up in the liver (hepatic steatosis), and at least one metabolic risk factor. When there is also increased alcohol intake, the term MetALD, or metabolic dysfunction and alcohol associated/related liver disease is used, and differentiated from alcohol-related liver disease (ALD) where alcohol is the predominant cause of the steatotic liver disease. The terms non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH, now MASH) have been used to describe different severities, the latter indicating the presence of further liver inflammation. NAFL is less dangerous than NASH and usually does not progress to it, but this progression may eventually lead to complications, such as cirrhosis, liver cancer, liver failure, and cardiovascular disease.

Obesity and type 2 diabetes are strong risk factors for MASLD. Other risks include being overweight, metabolic syndrome (defined as at least three of the five following medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum HDL cholesterol), a diet high in fructose, and older age. Obtaining a sample of the liver after excluding other potential causes of fatty liver can confirm the diagnosis.

Treatment for MASLD is weight loss by dietary changes and exercise; bariatric surgery can improve or resolve severe cases. There is some evidence for SGLT-2 inhibitors, GLP-1 agonists, pioglitazone, vitamin E and milk thistle in the treatment of MASLD. In March 2024, resmetirom was the first drug approved by the FDA for MASH. Those with MASH have a 2.6% increased risk of dying per year.

MASLD is the most common liver disorder in the world; about 25% of people have it. It is very common in developed nations, such as the United States, and affected about 75 to 100 million Americans in 2017. Over 90% of obese, 60% of diabetic, and up to 20% of normal-weight people develop MASLD. MASLD was the leading cause of chronic liver disease and the second most common reason for liver transplantation in the United States and Europe in 2017. MASLD affects about 20 to 25% of people in Europe. In the United States, estimates suggest that 30% to 40% of adults have MASLD, and about 3% to 12% of adults have MASH. The annual economic burden was about US$103 billion in the United States in 2016.