Development and testing of a bioartificial liver

Management of patients with acute severe liver failure is a major clinical challenge. We need to understand better normal and abnormal liver physiology, develop methods of assessing the degree of liver dysfunction, standardize methods of intervention and develop rational procedures to support the acutely failing liver until it either recovers or is replaced. Investigators have attempted to support animals and patients with liver insufficiency, utilizing various extracorporeal support systems including cross-circulation, whole liver blood perfusion, hemadsorption, hemodialysis, plasma exchange, total body wash-out, use of microsomal enzymes bound to artificial carriers and other. None of these therapeutic modalities succeeded in gaining wide clinical acceptance. Charcoal hemoperfusion has been used to treat severe acute liver failure with mixed results. Although there is clear experimental evidence that the technique has some beneficial effects, a controlled prospective clinical study failed to demonstrate significant clinical advantages. Other methods which relied primarily upon blood detoxification, showed limited success as well. Thus it appears that, at least for now, whole organ transplantation remains the only method with clinically-proven efficacy for treating severe acute liver failure. In attempting to develop systems for temporarily supporting patients until an organ becomes available for transplantation and because of the complexity and vast number of metabolic and other physiologic functions provided by the liver, it was felt that to provide effective ex vivo liver support, either utilization of whole organ perfusion or construction of a liver support system utilizing intact, viable, functioning isolated liver cells will be needed.