New insights into therapeutic strategies for targeting hepatic macrophages to alleviate liver fibrosis

Abstract

Liver fibrosis is a wound-healing response induced by persistent liver damage, resulting from complex multicellular interactions and multifactorial networks. Without intervention, it can progress to cirrhosis and even liver cancer. Current understanding suggests that liver fibrosis is reversible, making it crucial to explore effective therapeutic strategies for its alleviation. Chronic inflammation serves as the primary driver of liver fibrosis, with hepatic macrophages playing a dual role depending on their polarization state. This review summarizes various prevention and therapeutic strategies targeting hepatic macrophages in the context of liver fibrosis. These strategies include inhibition of macrophage recruitment, modulation of macrophage activation and polarization, regulation of macrophage metabolism, and induction of phagocytosis and autophagy in hepatic macrophages. Additionally, we discuss the communication between hepatic macrophages, hepatocytes, and hepatic stellate cells (HSCs), as well as the current clinical application of anti-fibrotic drugs targeting macrophages. The goal is to identify effective therapeutic targets at each stage of macrophage participation in liver fibrosis development, with the aim of using hepatic macrophages as a target for liver fibrosis treatment.

Keywords: Cell therapy; Macrophages polarization; Macrophages recruitment; Phagocytosis and autophagy; Programmed metabolism.