Dx Dialogues: Treating MASH

MASH is also known as metabolic dysfunction associated steatohepatitis and is the advanced form

of nonalcoholic fatty liver disease.

Hello. I'm Dr. Aja McCutchen, a physician partner at Atlanta Gastroenterology.

MASH, formerly known as NASH, or Nonalcoholic Steatohepatitis, is the advanced form of Nonalcoholic Fatty Liver

Disease, also known as NAFLD. It affects about 15 million people in the United States.

MASH is characterized by more than 5% liver fat without any other explanation, liver inflammation

and injury, and sometimes scarring, known as fibrosis.

Those living with MASH are at an increased risk of liver complications, with about 50% developing cirrhosis within 10

years, and the risk of hepatocellular carcinoma and liver-related deaths are increased by 10-fold.

In the United States, routine screening for NAFLD and MASH is not recommended as liver enzyme levels tend to be normal even in patients living with NAFLD.

Imaging doesn't distinguish well between NAFLD and MASH. However, transient elastography and magnetic resonance

elastography have been shown to reliably detect fibrosis.

Losing 10% of their weight can resolve MASH in up to 90% of patients, with 45% experiencing

fibrosis regression.

In March of 2024, resmetirom became the first therapy approved by the FDA to treat adult patients with MASH

with moderate to severe fibrosis. In a phase III trial with approximately 1,000 participants, 80- and 100-milligram doses

of resmetirom were tested against placebo. MASH was resolved in up to 30% without worsening fibrosis

versus 10% in the placebo group. Fibrosis was improved in up to 26% of participants,

with no worsening of NAFLD activity, versus 14% with the placebo. At both doses, cholesterol levels also decline.

Adverse events in the trial were reported at similar rates across all three groups, ranging from 10.9% to 12.7%.

In addition to resmetirom, other therapies are emerging as potential options for the treatment of MASH, including

some off-label treatments. Pioglitazone, for example, has been shown to improve MASH

but does not significantly reduce fibrosis. Injectable GLP-1s are also very effective in resolving MASH.

In a phase II trial, tirzepatide showed improvement in fibrosis in more than half of patients without worsening MASH

versus 30% in the placebo group. Injectable pegozafermin and lanifibranor