Hepatic Steatosis

Hepatic Steatosis

Hepatic steatosis, now classed under metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), means fat in >5% of liver cells without significant alcohol use. It is the most common chronic liver condition worldwide, affecting an estimated 25–30% of adults, and is far more common in people with obesity, type 2 diabetes and metabolic syndrome. It ranges from simple fatty liver, which is usually harmless, to metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH), where liver cell injury and inflammation can progress to scarring (fibrosis) and cirrhosis.

Fatty liver develops from insulin resistance in the liver, more fat made in the liver, less fat burned and runaway fat breakdown in fat tissue that floods the liver with free fatty acids. Glucagon plays a central role in liver fat metabolism by promoting fat burning and ketone production, and weaker glucagon action in the liver has been linked to fatty liver. That link makes activating the glucagon receptor an especially attractive way to treat MASLD/MASH.

Retatrutide has cut liver fat dramatically in clinical studies. In the Phase 2 obesity trial, people on the highest dose saw an average liver fat reduction of about 80–90%, and many returned to normal levels. The results come both from glucagon’s direct effects on the liver (more fat burning and less fat production) and from the indirect benefit of large weight loss. Eli Lilly has started a dedicated Phase 3 trial of retatrutide specifically for MASH resolution, a sign of its potential in this condition.