[Development of a hybrid bio-artificial liver].

Despite recent advances in medical management, fulminant hepatic failure (FHF) is still associated with high mortality. Liver transplantation is currently the only effective therapy for patients with FHF in many countries, but not yet in Japan. Thus, it is needed to introduce a bioartificial liver (BAL) support system using hepatocytes that substitutes for insufficient metabolism until the liver can recover. To function as a surrogate liver, BAL must meet two metabolic criteria: the first criterion requires highly differentiated liver cells; the second requires a mass sufficient to support the needs of the patients. Cell-extracellular matrix interaction is biologically relevant to regulating gene expression and maintaining cell differentiation of hepatocyte through activating liver-enriched transcriptional factors, including hepatocyte nuclear factor-1 (HNF-1) and HNF-4. With the advance of biotechnology, clinical trials of BAL using porcine primary hepatocytes or human hepatoblastoma cell lines have been successfully performed in the United States. In the near future, a hybrid liver support system is expected to be widely used for treating patients with FHF.