Metabolic Dysfunction-Associated Steatohepatitis: Is there evidence for fractured CD4+ T cell tolerance in the immunopathogenesis of MASH?

Metabolic dysfunction-associated liver disease (MASLD) is defined by hepatic steatosis with concomitant metabolic risk factors and is the leading cause of chronic liver disease. In approximately one-third of individuals, the disease progresses to metabolic dysfunction-associated steatohepatitis (MASH), a more severe form encompassing steatosis with inflammation and hepatocellular injury predisposing to liver failure, cirrhosis, and hepatocellular carcinoma. The mechanism(s) responsible for this aberrant inflammation are unknown. In this review, we explore the breakdown of the hepatic tolerogenic environment in MASH with discussion on fractured CD4+ T cell tolerance as an integral driver of the progression of MASLD to MASH.