MASLD and Liver Cancer: What’s the Link?
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition where too much fat builds up in your liver. Unlike fatty liver caused by heavy drinking, MASLD develops because of other health reasons and used to be called non-alcoholic fatty liver disease (NAFLD).
A more advanced form of MASLD, called metabolic dysfunction-associated steatohepatitis (MASH), happens when fat in your liver leads to inflammation and sometimes liver scarring (fibrosis).
What is hepatocellular carcinoma (HCC)?
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, making up about 90% of cases. Unlike secondary liver cancer – which spreads to your liver from other parts of the body – HCC starts in the liver.
Other less common types of liver cancer include:
- Intrahepatic cholangiocarcinoma: Cancer of the bile ducts inside the liver.
- Hepatoblastoma: A rare liver cancer that mostly affects children younger than 3.
Can fatty liver cause liver cancer?
Yes, it can. While most people with fatty liver don’t get liver cancer, MASLD is now seen as one of the fastest-growing causes of HCC.
Here’s how it happens:
- When fat builds up in your liver, it can lead to chronic inflammation.
- Inflammation that doesn’t go away can damage liver cells and their DNA.
- Over time, you may get scarring that doesn’t heal (cirrhosis).
- Cirrhosis creates an ideal setting for liver cancer to develop.
Though cirrhosis greatly increases the risk of HCC, liver cancer can also happen in people with MASLD who don’t have cirrhosis.
How common is liver cancer with fatty liver disease?
The risk of liver cancer mostly depends on how advanced your liver disease is. Here’s what research shows:
- Up to 2.6% of people with MASH develop HCC each year.
- If you have MASLD with cirrhosis, you’re 10-30 times more likely to develop HCC than people without cirrhosis.
- Around 0.11% of people with MASLD without cirrhosis may get HCC each year.
A growing number of people with MASLD without cirrhosis are getting liver cancer. Experts aren’t sure why. Researchers are working to find what specific factors increase the risk in these cases.
How Does MASLD Progress to Liver Cancer?
MASLD usually doesn’t cause much liver damage unless it progresses to MASH, the more severe form of the condition. Studies show about 20% of people with MASLD develop MASH, and of those, 10-25% may develop cirrhosis over 10-20 years.
Inflammation caused by conditions like MASH make the liver more vulnerable to cancer. Here’s how MASLD can lead to hepatocellular carcinoma (HCC):
- Excess fat cells damage or kill liver cells, a process called lipotoxicity.
- Damaged cells trigger inflammation, leading to MASH.
- MASH-related inflammation causes scar tissue to replace healthy tissue (fibrosis).
- The liver responds by creating new cells to repair itself.
- Constant cell turnover raises the risk of DNA damage, which can lead to cancer.
Who’s most at risk for MASLD-related liver cancer?
While cirrhosis is the main predictor of HCC, it doesn’t account for all cases. Research suggests that around 30% of people with MASLD-HCC don’t have cirrhosis, meaning liver cancer can develop before you get advanced scarring.
Other Factors That Can Increase Liver Cancer Risk
Obesity and type 2 diabetes raise the chances you’ll get HCC. These conditions can cause harmful inflammation and cell damage. A genetic predisposition, such as mutations in the PNPLA3 gene, can also affect how the liver processes and stores fat.
Other factors that increase your liver cancer risk include:
- Age over 50
- Being male
- Family history of liver cancer
- Hepatitis B or C infection
- Heavy alcohol consumption
- Smoking
Certain rare metabolic conditions can also raise liver cancer risk, such as:
- Untreated hereditary hemochromatosis (too much iron in the liver)
- Alpha-1 antitrypsin deficiency (a protein deficiency that affects the liver)
- Glycogen storage disease (an inherited disorder that affects sugar storage)
- Porphyria cutanea tarda (a condition that causes excess iron in the liver)
- Wilson disease (causes excess copper in the liver)
If you have MASLD, talk to your doctor about other risk factors.
Fatty Liver vs. Liver Cancer Symptoms
You may not have any symptoms. But general signs of fatty liver may include:
- Tiredness even with enough rest
- Weight loss without trying
- Not feeling hungry
- Pain or fullness in the upper right side of your belly
Symptoms of liver cancer may include:
- A hard lump right below your right rib cage
- A swollen belly
- Pain near your right shoulder blade or in your back
- Getting full when you eat small amounts of food
- No appetite
- Pale, white bowel movements
- Fever
- Yellowing of skin and whites of eyes (jaundice)
Your liver can do its job for a long time even when it’s damaged, so symptoms of fatty liver disease or liver cancer may not show up early on. When they do become noticeable, they often seem like symptoms of other health conditions, which can make it hard to know what’s wrong.
Screening
Health guidelines suggest liver cancer screenings only for people who are most at risk for getting the disease. Your chances of liver cancer are higher if you have:
- Chronic hepatitis B or C infections
- Liver cirrhosis, regardless of the underlying cause
- Inherited metabolic diseases (see previous section on risk factors)
- Autoimmune hepatitis
If you have cirrhosis, your doctor may suggest you get a liver ultrasound every six months to check for early signs of liver cancer. They might also run liver-specific blood tests at the same time.
Who might benefit from screening without cirrhosis?
Early detection and management can improve your chances of a good outcome if you do get liver cancer. But medical experts don’t agree on whether screenings are worth it for people without advanced liver scarring.
Some research suggests people with type 2 diabetes and MASLD should be considered for regular liver screenings, even without cirrhosis, since liver cancer can develop earlier in these settings. But there aren’t clear screening guidelines for this group.
How will I know if I develop liver cancer?
Your liver is located in the upper right side of your belly, just beneath your ribs. You may not be able to see or feel signs of liver cancer until you get a big mass in it. But there are things you can do to find liver cancer before that.
To diagnose liver cancer, you may get one more of the following:
- Blood tests. Alpha-fetoprotein (AFP) is a protein your liver makes before you're born. High levels of AFP can be a sign of liver cancer because levels should be low in adults.
- Imaging. Ultrasound, CT scans, MRI, or angiography can reveal swelling, masses or other abnormal changes in the liver.
- Liver biopsy. Your doctor may take out a small piece of liver tissue to test it for cancer cells. This usually isn’t necessary, but you might need a biopsy if other tests can't confirm a cancer diagnosis.
What Happens If I Get Liver Cancer?
Treatment for liver cancer depends on how far your cancer has spread, your age, and your overall health. To find the best treatment plan, your doctor will consider the following:
- The size of your tumor
- If you have cirrhosis
- How healthy you are
- Your cancer stage
Common treatments for liver cancer or its symptoms include:
- Surgery to take out the tumor
- Liver transplant
- Radiation
- Heat that destroys the the tumor (ablation therapy)
- Stopping the blood flow to the tumor (transarterial chemoembolization or radioembolization)
- Targeted drug therapy
- Immunotherapy
- Chemotherapy
At any point after your diagnosis you can get palliative care. That’s a type of supportive treatment that aims to improve your quality of life or help you manage side effects from cancer or its treatment.
If other treatments don’t work for you or aren’t an option, ask about clinical trials. These are studies that provide top-notch medical care but test new or experimental treatments that haven’t been approved for the general public.
How to Prevent MASH and MASLD From Progressing to Liver Cancer
You can start by managing the underlying causes of liver damage. For MASLD-related liver cancer, here are steps you can take to reduce your risk:
Manage your weight. If you are overweight or have obesity, losing weight is one of the best ways to reduce liver fat and inflammation. Even modest weight loss can make a big impact:
- Losing 3%-5% of your body weight can reduce fat buildup in your liver.
- A 7%-10% loss can improve inflammation linked to MASH.
- Losing at least 10% can decrease or reverse mild scarring (fibrosis).
Eat a liver-friendly diet. While there’s no specific “liver cancer diet,” a Mediterranean-style diet is widely recommended for liver and overall health. This eating plan includes a lot of plant-based foods, which can lower your risk of liver damage.
Dietary factors that may protect against liver cancer include:
- Eat more fruits, vegetables, whole grains, nuts, and legumes.
- Limit added sugars in foods and drinks.
- Avoid red and processed meat, which are high in saturated fats.
- Use unsaturated fats like olive oil instead of butter or margarine.
- Eat fish and seafood a couple times a week.
- Drink two to three cups of coffee a day.
Studies show regular coffee drinkers are less likely to get MASLD, advanced liver scarring, and liver cancer. Caffeine, in particular, may help lower the risk of HCC. But more research is needed to know exactly why coffee helps with liver health.
And if you have MASLD, alcohol is a no-go – it can speed up liver damage.
Get moving. Even if you don’t lose weight, regular physical activity can improve liver health. Aim for at least 30 minutes of exercise five days a week.
Some examples of aerobic or resistance exercises include:
- Brisk walking
- Jogging
- Cycling
- Lifting weights
- High-intensity interval-training (HIIT)
Consider medications. There’s no drug treatment for simple fatty liver. But a drug called resmetirom (Rezdiffra) has been approved to treat adults with MASH who have moderate to advanced liver scarring (but not cirrhosis).
Drugs can also help to manage other MASLD-related health conditions, such as:
- Type 2 diabetes
- High cholesterol
- Obesity
- High blood pressure
Ask your doctor if newer weight loss drugs, like GLP-1 agonists, might be right for you.
What Other Cancers Can Happen With Fatty Liver Disease?
MASLD boosts your odds of several cancers outside of the liver. This includes gastrointestinal cancers such as:
- Colon
- Stomach
- Pancreas
- Esophagus
- Biliary duct
Fatty liver disease and its related health problems (like obesity and type 2 diabetes) also raise your risk of:
- Lung cancer
- Breast cancer
- Endometrial cancer
- Bladder or other urinary system cancers
- Thyroid cancer
Recap
MASLD is a fastest-growing cause of liver cancer, especially in people who have obesity and type 2 diabetes.
Maintaining a healthy weight, eating a balanced diet, and staying active can help lessen the chances you’ll get MASLD-related liver damage or that it’ll progress to liver cancer.
If you have MASLD, talk to your doctor about the risk factors for liver cancer and what screenings might be right for you. Successful treatment is more likely if you catch liver cancer early.
What is the leading cause of liver cancer?
Globally, the most common cause of hepatocellular carcinoma (HCC) is a chronic hepatitis B or hepatitis C infection. But as rates of obesity and type 2 diabetes go up, so do cases of MASLD-HCC.
Does MASH always lead to liver cancer?
No. While it’s hard to predict who’ll get liver cancer, around 2%-3% of people with MASH are diagnosed with it each year.
What happens if your fatty liver gets worse?
Fat buildup in your liver can cause inflammation and cell damage. Over time, scar tissue can replace healthy tissue. If you have a lot of liver scarring (fibrosis), you can get permanent damage (cirrhosis) that leads to liver failure. About 3% of people with fatty liver may get liver cancer.
Show Sources
Photo Credit: SciePro/Science Source
SOURCES:
Bubu A. Banini, MD, PhD, assistant professor of medicine and translational research director, Metabolic Health and Weight Loss Program, Yale School of Medicine; associate director, clinical and translational core, Yale Liver Center.
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