Advances in bioartificial liver devices

In light of the increasing incidence of liver disease and continuing shortage of donor organs, cell-based therapies are gaining attention as promising treatments for liver failure. Currently, several extracorporeal bioartificial liver devices are undergoing clinical evaluation. Their future use will depend on the choice and stabilization of the cellular component. Although cell lines offer a limitless cell source, primary hepatocytes may be preferred because of their broad expression of liver-specific functions. Xenogenic primary cells are available in large quantities, but immunologic and infectious concerns may necessitate the use of human cells or human-derived cells. To improve and maintain functional primary hepatocytes, bioreactor designs must provide architecture that supports cell attachment, cell-cell interaction, cell-matrix interaction, and potential for scale-up. While the safety of BAL devices has been established, there are no uniform standards of efficacy, which may vary with the etiology of the liver failure. Consensus is needed in clinical trial design, including choice of end points, use of controls, and indications for enrollment. Also, a better understanding of the interplay between liver regeneration and BAL therapy will be critical to optimizing the implementation of this modality.