The rationale for artificial liver support is based on the hypothesis that if essential liver functions can be restored during the critical phase of liver failure, it should be possible to improve the survival of patients with severe liver disease. In the case of bridge-to-transplantation, it should provide the patient sufficient metabolic support until a donor liver can be found and transplanted. Since the management of acute liver failure requires the replacement of the liver's myriad metabolic functions, the idea of a hybrid bioartificial liver (BAL) support system has been proposed. BAL systems incorporate a biological (hepatocytes) and a synthetic housing component (plastic housing shell and semipermeable membrane) coupled in such a way as to facilitate the delivery of essential liver functions. Of the several BAL designs that have been proposed, only the capillary hollow-fiber based systems have been rapidly developed for clinical trials. Capillary hollow-fiber based BAL devices are basically off-the-shelf artificial kidney membranes that have been modified for use as an artificial liver. However, most capillary hollow-fiber based BAL designs have inherent physical limitations of total diffusion surface area and capacity for hepatocyte mass. We have proposed a novel BAL design using microencapsulated hepatocytes to overcome these physical limitations. This new BAL design (UCLA-BAL) involves the direct hemoperfusion of a packed-bed column of microencapsulated porcine hepatocytes within an extracorporeal chamber. In extensive animal studies using a well-characterized animal model fulminant hepatic failure (FHF), we demonstrated that the UCLA-BAL system had superior diffusion surface area and a higher capacity for hepatocytes compared to conventional capillary hollow-fiber based BAL devices. UCLA-BAL treatment significantly (P<0.001), improved the survival rate of FHF animals and significantly (P<0.01) prolonged the survival time of similar animals with very severe liver injury. BAL treatment was convenient, easy to operate and well tolerated, and did not adversely affect the animal's hemodynamics during treatment. We therefore suggest that the UCLA-BAL is a significant improvement over conventional, first-generation, capillary hollow-fiber BAL systems.