Fatty liver: the most common disease you may not know you have

Fatty liver disease is estimated to affect around a third of adults worldwide. It is closely tied to obesity and type 2 diabetes, and it usually has no symptoms until it is advanced.

The liver normally holds some fat. The problem starts when fat builds up inside liver cells beyond what they can handle. In many people this stays stable for years. In others, the fat triggers inflammation and cell damage, which can lead to scarring, called fibrosis, and eventually cirrhosis. Because the liver rarely hurts, many people find out only through a routine blood test or an imaging scan done for another reason.

A new name

In 2023, the field renamed it. What was called NAFLD became MASLD, metabolic dysfunction-associated steatotic liver disease, to reflect that it is driven by metabolism, not just the absence of alcohol. Its inflammatory form, once called NASH, is now MASH.

I think the change is more than cosmetic. The old name defined the disease by what it was not. The new one points to the cause. It also moves away from language that some patients found stigmatizing, and it puts the condition where it belongs, alongside diabetes and heart disease as part of the same metabolic picture.

The first approved drug

For years there was no approved medication. In 2024, the US approved the first drug for MASH with liver scarring, resmetirom, which acts on a thyroid hormone receptor in the liver. It is a nuclear receptor, the same family of proteins at the center of the FBXW7 study I co-authored.

The liver’s fat balance is run by a small set of molecular switches, and those switches are drug targets.

Nuclear receptors are proteins that sense signals such as hormones and nutrients, then switch sets of genes on or off. In the liver, they help decide whether fat is stored or burned. A drug that nudges the right receptor in the right tissue can shift that balance. That is what makes this family such a natural place to look for treatments.

What controls the switch

Our work showed that FBXW7 controls nutrient-sensing nuclear receptors in liver cells, and that losing it lets fat build up. FBXW7 is part of the system that tags proteins for removal. When it is gone, the receptors it normally keeps in check stay active longer than they should, and the liver’s handling of fat goes off balance. The broader point: the liver’s fat balance is run by a small set of molecular switches, and those switches are drug targets.

What you can do now

For most people, the first line of management is still lifestyle: weight loss, physical activity and attention to blood sugar. These are not glamorous, but they act on the same metabolic drivers that cause the disease. Anyone with diabetes or obesity should consider asking their doctor whether their liver has been checked.

My perspective

I find this an encouraging moment. For a long time fatty liver disease was common, serious and largely untreatable with drugs. Now there is a first approved option, and it came from understanding a specific molecular switch. I expect more to follow as we learn which receptors, and which regulators of those receptors, matter most. Basic research on how liver cells control fat is not abstract. It is how treatments get found.