The heterogeneity of monocyte-derived macrophages in MASH pathogenesis

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the leading global cause of chronic liver disease. Its more severe inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), often progresses to cirrhosis and hepatocellular carcinoma. However, the pathogenic mechanisms underlying MASH remain insufficiently defined. Hepatic macrophages, particularly monocyte-derived macrophages (MDMs), have recently been identified as key mediators in disease progression. This review summarizes the current evidence on the heterogeneity of MDMs in MASH pathogenesis, focusing on distinct subsets and their roles in either promoting or resolving hepatic inflammation. Additionally, the review provides an in-depth exploration of the mechanisms driving MDM differentiation, which contribute to their functional diversity. A more comprehensive understanding of MASH pathogenesis is essential for the identification of novel and effective therapeutic targets.