Liver fibrosis: mechanisms of immune-mediated liver injury

Abstract

Liver fibrosis and its end-stage consequence, cirrhosis, represent the final common pathway of virtually all chronic liver diseases. Research into hepatic stellate cell activation, imbalance of the extracellular matrix synthesis and degradation and the contribution of cytokines and chemokines has further elucidated the mechanisms underlying fibrosis. Furthermore, clarification of changes in host adaptive and innate immune systems has accelerated our understanding of the association between liver inflammation and fibrosis. Continued elucidation of the mechanisms of hepatic fibrosis has provided a comprehensive model of fibrosis progression and regression. This review summarizes the current concepts of improvements that have been made in the field of fibrosis.

Figure 1

Initiation and maintenance of fibrogenesis. Activated hepatic stellate cells, bone marrow derived cells, portal fibroblasts, epithelial-to-mesenchymal transition (EMT) are source of myofibroblasts. The pathways of HSC activation include those that provoke initiation and those that maintain perpetuation. Initiation is stimulated by soluble stimuli such as toxins, HBV or HCV infection and oxidant stress signals. Following activation, these myofibroblasts are characterized by increased proliferation, migration and a relative resistance to apoptosis. Imbalances in collagen synthesis and degradation result in cirrhosis and liver failure. HBV, hepatitis B virus; HCV, hepatitis C virus; HSC, hepatic stellate cell; ROS, reactive oxygen species; TIMP, tissue inhibitor of metalloproteinase.