Experimental Research Of G-CSF Therapeutic Effect On Acute Hepatic Failure

Background: Acute liver failure (ALF) is a severe clinical syndrome, which is induced by massive hepatocellular necrosis that are caused by virus, drugs, autoimmune reactions and metabolic dysfunction etc. Hepatitis virus infection is the leading cause of ALF which induces severe hepatitis in our country. Although most patients were diagnosed as chronic severe hepatitis in clinical practice, the clinical courses were actually patients fall into ALF on the background of chronic hepatitis. ALF carries a very high mortality of 50-80% because of the lack of effective medical therapeutic measures. The key problems of ALF were the extensive hepatocyte necrosis and the compensation capacity of regeneration of the residue hepatocytes. The prevention of hepatocyte necrosis and the enhancement of liver regeneration are effective basis in exploration of new therapeutic options of ALF. Recently, new properties of granulocyte colony-stimulating factor (G-CSF) as a modulator of immune response was discovered. G-CSF affects the balance in the production of pro- versus anti-inflammatory cytokines induced by lipopolysaccharide (LPS). Since intestinal endotoxemia can stimulate monocyte-macrophage system to produce and release a lot of cytokines and mediators of inflammation which further aggravate liver injury and play an important role in the pathogenesis of ALF, we presume that G-CSF can block the development of ALF by changing the balance of pro- versus anti-inflammatory cytokines release. On the other hand, the potential of hemopoietic stem cells (HSCs) to give rise to hepatocyte were recognized with the penetrating stem cell observation. HSC can migrate into liver and reconstitute liver after massive hepatocyte necrosis and inhibition of hepatocytes proliferation simultaneously. We presume that G-CSF can promote liver regeneration by mobilizing HSCs to home to liver after liver injury as G-CSF has the ability to mobilize HSCs from...