Targeting macrophages in liver fibrosis.

Fibrosis results from excessive deposition of extracellular matrix (ECM) components following tissue injury. While initially protective, chronic injury drives pathological ECM accumulation, tissue remodeling, and organ dysfunction. In the liver, fibrosis represents a common endpoint of chronic diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD). Macrophages are central players of the fibrotic hepatic niche, modulating inflammatory signals, immune regulation, and tissue repair. Recent advances demonstrate that hepatic macrophages form a heterogeneous and highly dynamic compartment, adopting diverse activation states that extend far beyond the classical M1/M2 paradigm. Importantly, liver fibrosis is now recognized as a potentially reversible process, with resolution being closely linked to the reprogramming of macrophages towards restorative phenotypes characterized by enhanced efferocytosis, reduced pro-inflammatory signaling, and increased matrix degradation capacity. As a result, efforts to design macrophage-based therapeutic strategies are shifting from non-specific approaches such as inhibition of monocyte recruitment towards approaches that actively promote pro-resolution programs, including targeted