New research into fatty liver disease aims to help with early intervention

A new study brings researchers closer to a better understanding of the pathology of the fatty liver disease MASH, which stands for metabolic dysfunction-associated steatohepatitis.

MASH is a result of poor diet and obesity and results in serious damage to the liver. In MASH, the liver becomes filled with active and rapidly multiplying T cells, a type of immune cell.

In a study published in Hepatologyresearchers are investigating what these T cells look like and how they work in people with liver cirrhosis (a late stage of liver disease) and in an animal model of MASH.

“Our goal is to provide a more thorough understanding of the mechanisms that drive MASH. Better understanding could lead to people being diagnosed earlier or before the disease has reached such a late stage that a liver transplant may be the only treatment option ,” said the paper’s senior author Matthew Burchill, Ph.D., associate professor of medicine at the University of Colorado Anschutz Medical Campus.

MASH is a slow killer because the progression of the disease occurs over decades. Despite this, MASH is quickly becoming the most common liver disease worldwide.

It is estimated that approximately 40% of the adult population in the United States is obese, and approximately 14% of asymptomatic middle-aged individuals in the US have biopsy-proven MASH, according to a study in the United States. Journal of Hepatology.

Burchill and his team discovered at MASH that T cells proliferate and change function in response to harmful substances associated with a poor diet.

The study found that, like infections such as the Hepatitis C virus, CD8 is clonally expanded⁺ T cells accumulate in the livers of both humans and mice with MASH. This suggests a potential role for antigen-activated CD8⁺ T cells in the pathogenesis of MASH.

“Understanding this process could help identify the specific substances that cause T cell activation and growth in the liver during MASH. This insight could ultimately result in the development of a biomarker test that would allow physicians to monitor the progression of the disease and treat it before it reaches a late stage,” adds Burchill.

The study concludes that antigenic stimulation likely drives T cell accumulation and chronic exhaustion in MASH.

The authors report that further research is needed to understand the timing and persistence of antigen-driven T cell responses in the liver and their role in the progression and resolution of the disease.