MASLD and MASH: Fatty Liver Disease and Cancer Risk

You might be surprised to find out that liver disease isn’t only caused by heavy drinking. In fact, an increasing number of people are being diagnosed with liver disease with a much more common cause, which is fat buildup in the liver. Fatty liver disease can lead to a condition called MASLD, or metabolic dysfunction-associated steatotic liver disease, and increase the risk of liver cancer.

What are MASLD and MASH?

Today, more than a third of adults in the United States have MASLD. Experts expect this number to rise sharply in the next 30 years. New research shows that MASLD and its more severe form MASH, or metabolic dysfunction-associated steatohepatitis, are now recognized as major risk factors for liver cancer.

“Every year, about 11,000 new cases of liver cancer related to MASLD and MASH are diagnosed. While other causes of liver cancer have gone down, MASLD is becoming more common,” said Bert O’Neil, MD, an American Society of Clinical Oncology (ASCO) expert and medical oncologist with Community Health Network.

What causes MASLD and MASH?

Fat can build up in the liver for several reasons. In people with MASLD, previously known as NAFLD, or nonalcoholic fatty liver disease, the reason is usually excess body weight.

Having extra weight affects your entire body. Extra weight makes your internal organs work harder than normal. For example, excess weight can make the liver store more fat than it should. Too much fat in the liver can lead to inflammation. This is when MASLD becomes MASH, previously known as NASH or nonalcoholic steatohepatitis.

Over time, inflammation damages the liver cells. When that happens, healthy liver cells are replaced with scar tissue, or fibrosis. Scar tissue can prevent your liver from working normally, a condition known as cirrhosis.

Who is at risk for MASLD and MASH?

You’re more likely to develop MASLD and MASH if you have a family history of fatty liver disease or if you have excess weight or are living with:

• Obesity
• Type 2 diabetes
• High blood pressure
• High cholesterol

“MASLD may be partly genetic and partly environmental. Most people who develop MASLD have at least one of these risk factors, but not everyone,” said Amol Rangnekar, MD, a transplant hepatologist with MedStar Georgetown Transplant Institute.

Besides having excess weight, heavy alcohol use is another leading cause of fatty liver disease. For this reason, even drinking moderate amounts of alcohol can make MASLD worse. In many people, liver damage results from a combination of MASLD and regular alcohol use. “But it’s important to know that you don’t have to drink alcohol to get liver cirrhosis,” Dr. O’Neil said.

Signs and symptoms of MASLD

Many people with fatty liver disease, and even MASLD, don’t notice symptoms at first. Some common signs and symptoms include:

• Feeling very tired even with plenty of sleep
• Having pain or a heavy feeling on the right side of the belly
• Yellowish color of the skin or eyes, known as jaundice
• Swelling in the belly or legs
• Bruising easier than usual

How MASLD and MASH can affect your health

People with advanced cirrhosis from MASLD/MASH are at higher risk for:

• Liver failure
• Liver cancer, most commonly hepatocellular carcinoma (HCC)
• Other gastrointestinal cancers such as esophageal, stomach, and colon cancers
• Type 2 diabetes, if not already diagnosed
• Needing a liver transplant
• Heart disease, including heart attack and stroke

Most cases of MASLD don’t progress to MASH. Even so, it’s important to understand the long-term risks of having MASLD, including serious liver and heart problems.

Talk to your doctor about liver health

If you have one or more known MASLD risk factors, talk with your doctor. They can gather more information to assess your liver health and order any needed tests.

Since most people with MASLD don’t have any symptoms, it may be suspected during a physical exam or a routine test. The presence of fat in the liver is usually detected through a routine blood test that measures your liver enzyme levels, or transaminases. “Elevated transaminases are a warning sign that someone may have fatty liver disease serious enough to cause cirrhosis or cancer,” said Dr. O’Neil.

If your liver enzyme levels are higher than normal, ask your doctor what this means for you. You can also ask for a referral to a gastroenterologist or a hepatologist, specialists who can help find out why your test results are abnormal. They can also recommend next steps. For example, you may need more blood tests or detailed liver testing with an ultrasound.

“Early diagnosis and treatment can prevent MASLD from becoming MASH. For a long time, MASLD was an underrecognized disease. But as it becomes more common, we’ve gotten better at finding and diagnosing it,” said Dr. Rangnekar.

Ways to lower risk for liver disease

Monitoring your liver health can help identify problems early. You can take measures to help decrease your risk for MASLD, which can progress to MASH and eventually liver cancer. However, not all cases of liver disease and liver cancer can be prevented.

These steps to reduce risk can also help those with fatty liver disease manage the condition. Management can include lifestyle changes, medication, or both.

Limiting or avoiding alcohol helps protect the liver. For people living with fatty liver disease, drinking alcohol can make their condition and symptoms worse.  Drinking fewer alcoholic beverages or none at all can give the liver a chance to heal. This can help lower the risk of more serious problems.

Eating healthy and staying physically active are key to preventing many health problems, including liver disease. Getting to and staying at a healthy weight can improve overall health and liver function, and can help lower risk for liver cancer.

If you have excess body weight, talk to your doctor about a weight-loss plan that’s right for you. In addition to a healthy diet and physical activity, your doctor may recommend other approaches, such as surgery or medication like GLP-1 drugs. Weight loss can also help with related conditions, such as type 2 diabetes, high cholesterol, and high blood pressure.

“If you have or are at risk for MASLD, the most important thing you can do is lose weight. Weight loss can help reduce liver fat, decrease inflammation, and potentially reverse liver scarring. Even losing between 7% and 10% of your body weight can make a difference,” said Dr. Rangnekar.

Dr. Bert O’Neil is an ASCO member.