A recent study sheds light on the complexities surrounding the fatty liver disease known as MASH, or metabolic dysfunction-associated steatohepatitis. MASH is typically caused by an unhealthy diet and obesity, leading to serious liver damage. In this condition, the liver is inundated with active and rapidly proliferating T cells, which are a form of immune cell. The current study explores the characteristics and functions of these T cells in individuals with liver cirrhosis (a severe form of liver disease) and in a model involving animals with MASH.
A recent study sheds light on the complexities surrounding the fatty liver disease known as MASH, or metabolic dysfunction-associated steatohepatitis.
MASH results from an unhealthy diet and obesity, leading to significant liver damage. During MASH, T cells, an immune cell type, multiply and fill the liver.
The findings, published in Hepatology, investigate the nature of these T cells and their behavior in patients with liver cirrhosis and a corresponding animal model of MASH.
“Our objective is to deepen the understanding of the processes that drive MASH. Greater insights could lead to earlier diagnosis, preventing situations where a liver transplant becomes the only viable treatment option,” stated the study’s lead author, Matthew Burchill, PhD, an associate professor of medicine at the University of Colorado Anschutz Medical Campus.
MASH progresses slowly, often over decades. Nonetheless, it is increasingly recognized as the most common liver disease globally. Current estimates suggest that about 40 percent of adults in the United States are classified as obese, and around 14 percent of symptom-free middle-aged individuals in the US have been confirmed to have MASH via biopsy, according to a recent article in the Journal of Hepatology.
Burchill’s research team discovered that during MASH, T cells not only proliferate but also alter their function in response to harmful dietary factors.
The investigation revealed that, similar to infections like the Hepatitis C virus, expanded populations of CD8+ T cells infiltrate the livers of both humans and mice suffering from MASH. This indicates a potential function for antigen-activated CD8+ T cells in the development of MASH.
“Gaining insight into this process may help pinpoint the specific substances that trigger T cell activation and proliferation within the liver during MASH. Such knowledge could ultimately pave the way for a biomarker test that enables healthcare providers to monitor and address disease progression before it reaches a critical stage,” Burchill adds.
The research suggests that the accumulation of T cells and their chronic exhaustion in MASH are likely driven by antigenic stimulation.
The authors note that additional research is necessary to clarify the timing and duration of antigen-driven T cell responses in the liver and their implications for disease progression and potential recovery.
