The immunometabolic nature of MASH: framing immune cells within metabolic dysfunction

Metabolic dysfunction-associated steatohepatitis (MASH) is a major challenge in hepatology. Despite considerable progress in our understanding of MASH, the particular mechanisms underlying disease development and the variable progression among patients with similar clinical risk factors remain inadequately explained. The liver contains one of the most varied populations of resident immune cells in the body. Accumulating evidence indicates that immune activity substantially influences the clinical trajectory of hepatic diseases. Myeloid and lymphoid cell subsets respond differently to local signals, either sustaining inflammation or facilitating tissue repair and disease remission. In MASH, metabolic and immunological pathways reinforce each other, creating a self-perpetuating pathogenic circuit. The hepatic microenvironment reprograms the metabolism and function of immune cells, while aberrant immune responses intensify hepatic metabolic stress. Consequently, MASH should be recognized as an immunometabolic disorder. Immune dysregulation is not simply a secondary effect of metabolic dysfunction but a principal driver of disease progression. Therefore, immune modulation is a central therapeutic approach. Addressing the complexity of MASH requires a thorough comprehension of hepatic immune dynamics. This review examines recent findings that place immune cells at the core of MASH pathogenesis and contends that effective management should integrate metabolic and immunological perspectives.