Reversibility of Liver Fibrosis and Inactivation of Fibrogenic Myofibroblasts

Abstract

Many studies have demonstrated that hepatic fibrosis is reversible. Regression of liver fibrosis is associated with resorption of fibrous scar and the disappearance of collagen-producing myofibroblasts. The fate of these myofibroblasts has been recently revealed: some myofibroblasts undergo senescence and apoptosis during reversal of fibrosis, whereas other myofibroblasts revert to a quiescent-like phenotype. Inactivation of myofibroblasts is a newly described phenomenon (Kisseleva et al. in Proc. Natl.Acad. Sci. USA 109:9448–9453, 2012) which now requires mechanistic investigation. Understanding the mechanism of inactivation of hepatic stellate cells on cessation of fibrogenic stimuli may identify new approaches to cause already existing activated hepatic stellate cells/myofibroblasts to revert to a quiescent-like state. This review summarizes the research on the inactivation of hepatic myofibroblasts.