A new study brings researchers closer to a better understanding of the pathology of fatty liver disease (MASH), which stands for metabolic dysfunction-associated steatohepatitis.
MASH is a result of poor nutrition and obesity and causes severe damage to the liver. In MASH, the liver becomes filled with active and rapidly multiplying T cells, which are a type of immune cell.
In today’s study, published in HepatologyResearchers are examining what these T cells look like and how they function in people with cirrhosis of the liver (an advanced stage of liver disease) and in an animal model of MASH.
“Our goal is to provide a more complete understanding of the mechanisms that drive MASH. Better understanding may lead to people being diagnosed earlier or before the disease is at such an advanced stage that a liver transplant may be the only treatment option,” said the paper’s senior author, Matthew Burchill, PhD, associate professor of medicine at the University of Colorado Anschutz Medical Campus.
MASH is a slow-killing disease, with progression occurring over decades. Despite this, MASH is rapidly becoming the most prevalent liver disease worldwide. It is estimated that approximately 40 percent of the adult population in the United States is obese and approximately 14 percent of asymptomatic middle-aged people in the United States have biopsy-proven MASH, according to a recent study published in the journal Journal of Hepatology.
Burchill and his team discovered that during MASH, T cells multiply and change their function in response to harmful substances associated with poor diet.
The study showed that, similar to infections such as hepatitis C virus, clonally expanded CD8+ T cells accumulate in the livers of humans and mice with MASH. This suggests a possible role for antigen-activated CD8+ T cells in the pathogenesis of MASH.
“Understanding this process may help identify the specific substances that trigger T cell activation and growth in the liver during MASH. This understanding could lead to the development of a biomarker test that will allow doctors to track and treat the progression of the disease before it reaches an advanced stage,” Burchill adds.
The study concludes that antigenic stimulation likely drives T cell accumulation and chronic exhaustion in MASH.
The authors mention that further studies are needed to understand the timing and persistence of antigen-driven T cell responses in the liver and their role in disease progression and resolution.