Macrophages: Central regulators of hepatic fibrogenesis and fibrosis resolution

Hepatic fibrosis is the common end point to chronic injury of varied aetiology. There is now excellent evidence in both human studies and animal models that liver fibrosis is a bidirectional process with a significant reversible component. The hepatic stellate cell (HSC), following activation to a myofibroblast phenotype, is the principal cell producing extracellular matrix (ECM) during fibrogenesis and is the main source of TIMP-1, which inhibits the endogenous matrix-degrading activity of matrix metalloproteinases (MMPs), thus promoting scar deposition. Furthermore, apoptosis of activated HSCs is a critical feature of scar resolution. However, emerging evidence indicates that it is the hepatic macrophage that is the master regulator of this dynamic fibrogenesis–fibrosis resolution paradigm.