For many years, doctors believed that a common liver disease known as metabolic dysfunction-associated steatotic liver disease, or MASLD, was mostly caused by lifestyle choices such as diet and exercise, combined with some genetic influence.
MASLD was previously called nonalcoholic fatty liver disease. But a new study from Mayo Clinic’s Center for Individualized Medicine has changed that belief.
In a surprising discovery, scientists have found that a rare mutation in one single gene can directly cause MASLD in some people. This means that for certain patients, the disease is not just about lifestyle—it may be passed down in their family through their genes. The research was published in the journal Hepatology.
The mutation is in a gene called MET. This gene helps the liver heal and controls how the body handles fat. When the MET gene doesn’t work properly because of this mutation, fat builds up in the liver. This buildup can cause swelling and irritation.
Over time, it can lead to scarring of the liver, which is called fibrosis. In severe cases, the damage becomes worse and turns into cirrhosis. Cirrhosis is a serious condition that can lead to liver failure or even cancer.
MASLD is very common. About one in three adults around the world have it. A more serious version of the disease, called metabolic dysfunction-associated steatohepatitis or MASH, is becoming one of the top reasons people need liver transplants.
Dr. Filippo Pinto e Vairo, the main author of the study, said this discovery gives us new insight into how this liver disease starts and how we might treat it in the future. He explained that rare inherited changes in genes can sometimes be the main cause of common illnesses.
The research began with one woman and her father. They both had MASH, but they didn’t have any of the usual risk factors like diabetes or high cholesterol. Scientists studied their DNA closely, looking at over 20,000 genes. They found a tiny change—just one letter different—in the MET gene. This change stopped their livers from handling fat the right way.
To make sure the finding was real, Mayo Clinic worked with researchers from the Medical College of Wisconsin. Dr. Raul Urrutia and his team showed how this small change in the MET gene messed up the gene’s instructions.
This caused the liver to stop processing fat normally. What makes this discovery more important is that the specific mutation had never been seen before in any genetic databases.
Dr. Urrutia explained that rare diseases like this can hide inside common ones. This study shows how powerful genetic testing and personalized medicine can be.
To find out how common this gene mutation is, researchers looked at data from Mayo Clinic’s Tapestry study.
This project has analyzed DNA from over 100,000 people across the U.S. Out of nearly 4,000 people in the study who had MASLD, about 1% had rare changes in the MET gene. Among those, 18% had mutations in the same region of the gene as the family from the original case.
Dr. Konstantinos Lazaridis, one of the study’s lead authors, said this could affect hundreds of thousands, or even millions, of people. He also said this is one of the first big findings from the Tapestry study and shows how useful large DNA studies can be in uncovering hidden causes of diseases.
Mayo Clinic has been a leader in using genetic research to solve medical mysteries. Since 2019, its Program for Rare and Undiagnosed Diseases has helped more than 3,200 patients.
It works with almost 300 doctors from many different areas of medicine. The goal is to find better diagnoses for people with rare or hard-to-explain conditions, including liver problems.
The next step is to learn more about how this mutation affects the liver and whether it can help create new treatments. If doctors can find people with these gene changes early, they may be able to give them care that fits their needs and possibly stop the disease before it gets worse.
This discovery is not just about one family. It offers a new way to understand and treat MASLD, and it shows the power of modern genetic science. One day, this might help prevent liver disease in many people through personalized care based on their DNA.
If you care about liver health, please read studies that refined fiber is link to liver cancer, and the best and worst foods for liver health.
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