Fatty Liver Disease Affects 1 in 4 People — A New Treatment Shows Promising Results

It may not grab headlines like heart disease or diabetes, but fatty liver disease—now known as MASLD (metabolic dysfunction-associated steatotic liver disease)—affects about one in four people worldwide. When left untreated, it can progress into MASH (metabolic dysfunction-associated steatohepatitis), a more severe form that causes liver inflammation, scarring, and potentially liver failure.

While lifestyle factors like poor diet, obesity, and lack of physical activity contribute to MASLD and MASH, scientists are now uncovering deeper, cellular-level causes—and one molecule is emerging as a key player: NAD+.

What Is NAD+ and Why Does It Matter?

NAD+ (nicotinamide adenine dinucleotide) is a crucial molecule your body needs to generate energy, repair cellular damage, and support healthy liver function. But in people with fatty liver disease, NAD+ levels tend to drop, making it harder for liver cells to recover from stress and injury.

Now, a groundbreaking study led by Johan Auwerx and his research team at the École Polytechnique Fédérale de Lausanne in Switzerland has found a way to boost NAD+ levels by targeting a key liver enzyme—ACMSD.

The Breakthrough: Blocking ACMSD to Restore Liver Health

The enzyme ACMSD (alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase) acts like a gatekeeper in NAD+ production. If this enzyme is overactive, your body can’t produce enough NAD+—especially in the liver.

To fix this, the Swiss team developed a new drug, TLC-065, which works by blocking ACMSD activity. The result? Higher NAD+ levels, healthier liver cells, and reduced liver inflammation and scarring.

How the Treatment Works: Results in Mice and Lab-Grown Human Livers

In their study, mice fed a high-fat diet developed symptoms of MASLD and MASH. But after being treated with TLC-065, their livers showed:

• Less inflammation

• Reduced fibrosis (scarring)

• Better mitochondrial function

• Improved DNA repair mechanisms

Even more exciting, the researchers tested TLC-065 on lab-grown human liver tissue, and the treatment worked just as well—showing a potential pathway to human clinical trials.

One of the study’s most important insights is the link between DNA damage and liver disease progression. As NAD+ levels increased, cells were better able to repair damaged DNA, helping the liver to recover and function more normally.

Why This Matters: A New Approach to Treating Fatty Liver Disease

Until now, most approaches to MASLD and MASH have focused on lifestyle changes—like diet, exercise, and weight loss. While these remain essential, this new research opens the door to a medication-based therapy that works on a molecular level.

By boosting the body’s natural ability to heal through NAD+ restoration, scientists may be able to halt or even reverse liver damage caused by fatty liver disease. And because NAD+ is involved in so many aspects of cellular health, this research could have implications for other conditions too—including metabolic disorders, inflammation, and aging-related diseases.

What’s Next for TLC-065?

While the early results are promising, TLC-065 still needs to undergo human clinical trials before it can be approved for use. But researchers are optimistic. The success seen in both animal models and human liver organoids suggests that this treatment could become a game-changer in the fight against fatty liver disease.

If approved, it could offer hope to the millions living with MASLD and MASH—many of whom may not even realize they have the disease until it’s advanced.