MASH: The Silent Liver Epidemic

What is MASH?

MASH (metabolic dysfunction-associated steatohepatitis) is a progressive liver disease characterized by fat accumulation, inflammation, and liver cell damage in people who drink little to no alcohol. It was previously called NASH (non-alcoholic steatohepatitis), but the name was changed in 2023 to better reflect its metabolic origins and reduce stigma.[1]

MASH exists on a spectrum:

The Silent Epidemic

MASH is called "silent" because it typically causes no symptoms until advanced stages. Most people are diagnosed incidentally: abnormal liver tests on routine bloodwork, or fatty liver seen on imaging for something else.

The numbers are staggering:

• 1 in 4 adults worldwide has fatty liver disease (MASLD)[2]
• About 20-30% of those with MASLD have MASH
• MASH is the fastest-growing indication for liver transplant
• By 2030, MASH is projected to become the #1 cause of liver transplant in the US

This tracks perfectly with the obesity and diabetes epidemics. MASH shares the same metabolic roots: insulin resistance, obesity, and metabolic syndrome.

How MASH Damages the Liver

The liver normally stores small amounts of fat. In MASLD/MASH, excess calories (particularly from sugar and refined carbohydrates) overwhelm the liver's capacity. The fat triggers:

1. Oxidative stress: Toxic reactive oxygen species damage liver cells
2. Inflammation: Immune cells infiltrate, trying to repair damage
3. Cell death: Hepatocytes balloon and die (ballooning degeneration)
4. Fibrosis: Repeated injury activates stellate cells, which produce scar tissue

Over years or decades, accumulated scar tissue can progress to cirrhosis, irreversible scarring that impairs liver function. Cirrhosis also dramatically increases the risk of hepatocellular carcinoma (liver cancer).[5]

Risk Factors

Diagnosis

Diagnosing MASH is challenging because:

• Blood tests (ALT, AST) can be normal even with significant disease
• Ultrasound can detect fat but not inflammation or fibrosis
• Liver biopsy remains the gold standard but is invasive

Newer non-invasive tools are improving diagnosis:

• FibroScan: Uses ultrasound elastography to measure liver stiffness (fibrosis)
• MRI-PDFF: Precisely quantifies liver fat
• Blood biomarkers: FIB-4, ELF test, and others estimate fibrosis stage

Treatment: Finally, a Breakthrough

For years, the only treatments were lifestyle modification: weight loss through diet and exercise. Losing 7-10% of body weight can resolve MASH in many patients. But sustaining weight loss is notoriously difficult.

In March 2024, the FDA approved resmetirom (Rezdiffra), the first drug specifically approved for MASH with moderate to advanced fibrosis.[3] It's a thyroid hormone receptor agonist that:

• Increases liver fat metabolism
• Reduces inflammation
• May slow or reverse fibrosis

GLP-1 agonists like semaglutide (Ozempic/Wegovy) also show significant promise. By causing weight loss and improving metabolic parameters, they can resolve MASH in many patients, though they're not yet FDA-approved for this indication specifically.

Prevention

MASH is largely preventable through the same strategies that prevent obesity and diabetes:

• Maintain healthy weight
• Limit added sugars and refined carbohydrates
• Regular physical activity
• Avoid excessive alcohol (even "moderate" drinking may worsen fatty liver)
• Control diabetes and metabolic syndrome

"The liver is remarkably resilient. If caught early, fatty liver disease is completely reversible. The key is awareness and action before cirrhosis develops."