Nonalcoholic Fatty Liver Disease and NASH

What happens in fatty liver disease

When the body takes in more energy than it uses, and especially when cells become resistant to insulin, fat accumulates inside liver cells. More than 5% fat in the liver is defined as fatty liver (steatosis).

Fibrosis stage is the best predictor of future liver problems. Most people with fatty liver never develop cirrhosis, but because so many people have it, MASLD is becoming a leading cause of cirrhosis, liver cancer and liver transplantation.

The name change

In 2023, international liver societies renamed NAFLD to MASLD and NASH to MASH, emphasizing the role of metabolic risk factors and avoiding stigmatizing terms. Nearly everyone with NAFLD meets the new definition. People with MASLD who also drink moderate amounts of alcohol are classed as MetALD.

Risk factors

• obesity, especially fat around the waist
• type 2 diabetes and prediabetes
• high blood pressure
• high triglycerides and low HDL cholesterol
• metabolic syndrome
• sleep apnea, polycystic ovary syndrome, underactive thyroid
• certain genetic variants (such as PNPLA3)
• Hispanic ancestry is associated with higher rates in the US

Lean people can also develop fatty liver, especially with insulin resistance.

Symptoms

Most people have no symptoms. Possible symptoms include:

• tiredness
• dull ache or fullness in the upper right belly
• an enlarged liver found on examination

Advanced fibrosis or cirrhosis can cause jaundice, belly swelling (ascites), leg swelling, easy bruising, confusion and vomiting blood.

Diagnosis

1. Blood tests: liver enzymes (ALT, AST) may be raised or normal; also blood sugar, cholesterol and tests to rule out other liver diseases (hepatitis B and C, iron overload, autoimmune).
2. Imaging: ultrasound commonly shows fatty liver.
3. FIB-4 score: a calculation using age, liver enzymes and platelet count to estimate fibrosis risk; recommended for people with risk factors.
4. Elastography: FibroScan (vibration-controlled transient elastography) or MR elastography measures liver stiffness and fat.
5. Liver biopsy: only when the diagnosis or stage is uncertain.

Treatment

Lifestyle (the foundation)

• Weight loss: losing 5% of body weight reduces liver fat; 7% to 10% can resolve NASH; 10% or more can improve fibrosis.
• Diet: a Mediterranean-style diet, fewer sugary drinks and refined carbohydrates, less ultra-processed food.
• Exercise: at least 150 minutes of moderate activity a week; resistance training helps even without weight loss.
• Alcohol: limit or avoid, especially with fibrosis.
• Coffee: regular coffee consumption is associated with lower fibrosis risk.

Medicines

• Resmetirom: the first medicine approved by the FDA (2024) specifically for MASH with moderate to advanced fibrosis, used with diet and exercise.
• GLP-1 receptor agonists such as semaglutide: help weight loss and improve MASH; semaglutide has also been approved for MASH with fibrosis.
• Pioglitazone: improves NASH in people with or without diabetes; may cause weight gain.
• Vitamin E: may help some people without diabetes with biopsy-proven NASH; long-term risks are debated.
• Statins: safe and recommended to reduce heart disease risk, the leading cause of death in people with fatty liver.

Bariatric surgery

For people with severe obesity, weight-loss surgery often resolves NASH and can improve fibrosis.

Cirrhosis care

People with cirrhosis need ultrasound screening for liver cancer every 6 months, monitoring for varices, and evaluation for transplant if the liver fails.

Complications

• cirrhosis and liver failure
• liver cancer, sometimes even before cirrhosis
• heart disease and stroke, which are the most common causes of death
• type 2 diabetes and chronic kidney disease

Frequently asked questions

What is the difference between NAFLD and NASH?

NAFLD is the overall condition of excess fat in the liver. NASH is a more serious form where the fat causes inflammation and liver cell damage, which can lead to scarring and cirrhosis. They have been renamed MASLD and MASH.

Can fatty liver disease be reversed?

Yes, often. Losing 7% to 10% of body weight through diet and exercise can reduce liver fat, resolve inflammation and even improve early scarring. Cirrhosis is much harder to reverse, so early action matters.

What are the symptoms of fatty liver?

Most people have no symptoms. Some notice tiredness or a dull ache in the upper right belly. Symptoms of advanced disease, such as yellow skin, swelling of the belly or legs, and confusion, appear only when significant scarring has developed.

What is the best diet for fatty liver?

A Mediterranean-style diet rich in vegetables, fruit, whole grains, legumes, fish, olive oil and nuts, with fewer sugary drinks, refined carbohydrates and processed foods, is recommended. Reducing calories to achieve weight loss is the key goal.

Is fatty liver disease dangerous?

Simple fatty liver usually is not, but it signals metabolic problems that raise heart disease risk. In a minority, it progresses to NASH, fibrosis, cirrhosis and liver cancer. Testing for fibrosis helps identify who needs closer monitoring.