Pathophysiology of liver regeneration

Liver mass is carefully regulated in animals and the ratio of body weight and liver mass is maintained constant under normal conditions. Nevertheless liver volume can vary enormously under different nutrition conditions. Infact liver mass decreases under fasting conditions and increases again when nutrition is restarted. In this case growth of liver mass is not due to cell proliferation. On the contrary it is known since the time of Prometeus that loss of liver tissue is replaced by hepatocyte proliferation. This is true not only when the tissue loss is due to an acute damage as it is the case after an acute viral hepatitis. During chronic damage because of persistence of the damaging noxae, replacement of tissue loss may not be successful and wound healing process may become prominent and lead to scar formation, to defective liver function and to liver cirrhosis and portal hypertension. Until recently it was thought that cirrhosis is not reversible. The possibility of liver transplantation has however offered the opportunity to concentrate on pathophysiology of liver cirrhosis and on pathophysiology of liver insufficiency (more in general acute as well as chronic). The experience of the last ten years has shown that liver function can normalize even when liver cirrhosis and portal hypertension were already established provided that the damaging noxae has been eliminated and the liver has been offered the chance to recover. Liver tissue loss may be replaced in several ways. It has however to be taken in consideration that damaged hepatocytes can not proliferate; this is the case for steatotic hepatocytes. In this case infact liver resection can lead to the clinical picture of liver failure. This can also happen when the remaining liver mass is to small or the burden of the damaging noxae is to high for the functioning liver mass left - as it may be the case in certain patients with fulminant hepatic failure. In some cases of alcoholic liver damage a functional liver failure may be the mayor clinical problem even when the liver mass is normal or increased. For all these cases bridging therapeutic measures can be life seaving and eather leed to functional recovery of the damaged hepatocytes or either allow hepatocyte proliferation or allow to reach liver transplantation when recovery is not possible. Besides the natural mechanisms of liver tissue replacement such as hepatocyte proliferation, oval cells development or possibly replacement of loss hepatocytes by bone marrow derived stem cells selective repopulation of damaged liver by administering isolated hepatocytes has been tried in different animal models. In human patients different bioactive systems using liver cells of different origins are beeing tested. Elimination of liver „toxins” by means of special dialysis devices may be helpful especially in those patients with preserved liver mass.