Innate Immunity and MASLD

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and the degree of fibrosis are key determinants of the prognosis. The pathophysiology of liver inflammation is incompletely understood and involves diverse factors and specifically innate and adaptive immune responses. More specifically, diverse mediators of innate immunity such as proinflammatory cytokines, adipokines, inflammasomes and various cell types like mononuclear cells, macrophages and natural killer cells are involved in directing the inflammatory process in MASLD. The activation of innate immunity is driven by various factors including excess lipids and lipotoxicity, insulin resistance and molecular patterns derived from gut commensals. Targeting pathways of innate immunity might therefore appear as an attractive therapeutic strategy in the future management of MASLD and possibly its complications.

Causal relationship between depression and metabolic dysfunction-associated steatotic liver disease: a bidirectional Mendelian randomized study

“…Although liver enzymes are correlated with inflammation, they are not linked to the metabolic dysregulation typically found in MASLD patients. Nevertheless, in up to 20–25% of MASLD cases, hepatic inflammation emerges, denoted as metabolic associated steatohepatitis (MASH) ( 47 ). This may lead to further hepatic complications, such as advanced fibrosis, cirrhosis, ultimately culminating in hepatocellular carcinoma (HCC) ( 48 ).…”