Nonalcoholic Steatohepatitis/Metabolic Dysfunction-Associated Steatohepatitis (NASH/MASH)

What is nonalcoholic steatohepatitis/metabolic dysfunction-associated steatohepatitis (NASH/MASH)?

NASH/MASH is a severe form of nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), a condition where fat accumulates in the liver. People with NASH/MASH experience liver fibrosis and inflammation, and are more likely to develop liver cancer, cardiovascular disease and type 2 diabetes. In tandem with the obesity epidemic, NAFLD/MASLD prevalence worldwide has doubled in the past 30 years, driving a significant increase in NASH/MASH – and there are currently no FDA-approved treatments.

Why has the disease name changed?

In 2023, a group of more than 200 physicians, public health experts, industry representatives, regulatory officials, and patient advocates voted to change NASH to MASH – changing “non-alcoholic” to “metabolic” in an effort to destigmatize and better represent the current understanding of the disease.

How does cortisol activity affect this disease?

Cortisol activity dysregulation has detrimental effects on the processes that contribute to liver fat buildup, which underlies NASH/MASH pathology. Cortisol is a glucocorticoid hormone (GC) secreted during stress, mainly to support recruitment of energy reserves. Endogenous GCs regulate metabolic pathways in the liver, including the stimulation of both hepatic influx and efflux of lipids.

How might cortisol modulation help?

Corcept leads the field in the research and development of selective glucocorticoid receptor modulators (SGRMs), which selectively modulate the effects of cortisol by reversibly binding to the glucocorticoid receptor (GR). We’re exploring how cortisol modulation may impact the fat deposits and other factors associated with MASH.