Developments in bioartificial liver research: concepts, performance, and applications

As an alternative to liver transplantation, numerous researchers have been working toward the goal of development of a fully functional artificial liver. In recent years, artificial liver support systems have been advocated as interim treatments for patients awaiting hepatocyte replacement therapy or liver transplantation; so-called "bridging" treatments. It is recognized that an effective artificial liver system requires: (1) a viable and highly functional hepatocyte cell line, (2) a suitable bioreactor environment and peripheral control systems, and (3) an effective extracorporeal circulatory system to incorporate an artificial liver system. Conventional systems have, however, suffered from various drawbacks, including incompatibility of cell cultures derived from non-human cells, insufficient cell proliferation, rapid deterioration of cellular function due to an impoverished cellular environment, and lack of system scalability. A newly established artificial liver system overcomes many of these problems and demonstrates a long-term capacity to maintain multiple liver-specific functions, such as protein synthesis, enzyme activity, and drug metabolism, both quantitatively and qualitatively. The present review provides an overview of the concepts underpinning artificial liver systems, the performance of presently available systems and the practical applications of available systems and those in development.