Metabolic dysfunction-associated steatotic liver disease

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition that is characterized by a buildup of fat in the liver, which can lead to liver damage. The liver is part of the digestive system, and it helps break down food, store energy, and remove waste products. If more than 5 percent of the liver contains fat, the liver is considered to be fatty (steatotic).

MASLD is most common among middle-aged or older people, although younger people, including children, may also be affected. People with MASLD have liver steatosis along with at least one of the following features: higher body weight, type 2 diabetes, or one of several metabolic abnormalities. The abnormalities that are included in the diagnosis of MASLD are pre-diabetes (insulin resistance), high levels of fats (lipids) such as cholesterol and triglycerides in the blood, or high blood pressure (hypertension). MASLD is estimated to occur in up to 75 percent of adults with obesity or high levels of lipids in the blood and in up to 65 percent of adults with type 2 diabetes.

In people with MASLD, the fat deposits in the liver can cause increased levels of liver enzymes that can be detected during routine blood tests. Some affected individuals have abdominal pain or fatigue. During a physical examination, the liver may be found to be slightly enlarged. In people with MASLD, the liver problems are not caused by alcohol use disorder.

MASLD is slow to worsen, or it may not worsen at all. In many affected individuals, the buildup of fat in the liver can be reduced by adopting healthy habits. However, up to 30 percent of people with MASLD develop inflammation of the liver (metabolic dysfunction-associated steatohepatitis, also known as MASH), which can damage the liver. In people with long-term liver damage, normal liver tissue may be replaced with scar tissue (fibrosis), resulting in permanent liver disease (cirrhosis) and, eventually, liver failure. People with MASLD, MASH, and cirrhosis have a higher risk of developing liver cancer (hepatocellular cancer). People with MASLD are also at increased risk of developing additional health problems such as heart (cardiovascular) disease.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

The specific causes of MASLD are unclear, although this condition is likely a result of both environmental factors and changes in several genes. Genetic changes that increase the risk of disease are called pathogenic variants.

When the amount of fat in a person's diet exceeds the amount the body can use, some of the fat is stored in the liver. Researchers suggest that a diet that is high in cholesterol, the refined sugars used in processed foods, and certain other nutrients may increase the likelihood of developing MASLD.

It is unclear what causes MASH and cirrhosis to develop in some people with MASLD. Researchers are studying several possible mechanisms. These include inflammation caused by an immune system reaction to the buildup of fat in the liver, toxic inflammatory chemicals (cytokines) released by the liver cells or fat cells, the self-destruction (apoptosis) of liver cells, and the effect of unstable molecules called free radicals (oxidative stress). The different populations of microorganisms in the intestines (gut microbiota) may also play a role in the development of MASLD and its progression to MASH.

Studies have identified many genetic changes that may be associated with the development of MASLD and MASH. Among these is a particular variant in the PNPLA3 gene. This gene provides instructions for making an enzyme that is found in fat and liver cells. The PNPLA3 enzyme likely helps process and store fats from the diet. The PNPLA3 gene variant that is associated with MASLD is thought to cause cells to produce an altered version of the enzyme that increases fat retention and decreases breakdown of fats in the liver. Genetic variants seem to only play a small role in the development of MASLD. Ongoing research will show how additional genetic changes contribute to the development of MASLD and its complications.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

An increased risk of developing MASLD can be passed down through generations in families, but the inheritance pattern is unknown.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

MASLD occurs in about 25 percent adults and 7 to 14 percent of children worldwide. It is the most common chronic liver disorder in Western countries, including the United States, and its prevalence is increasing along with the rising prevalence of obesity. It is estimated that MASLD will affect over half of individuals by 2040.

Which doctor should you see?

The suggested department for discussing Metabolic dysfunction-associated steatotic liver disease is Hepatology, with a hepatologist / gastroenterologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What is known about the cause and extent of liver involvement?
• Which medicines, supplements or exposures should be reviewed?
• What follow-up is appropriate for the specific diagnosis and stage?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Metabolic dysfunction-associated steatotic liver disease. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.