Extracorporeal liver support: Waiting for the deciding vote

Because acute liver cell failure is associated with an exceedingly high mortality, liver support has been proposed since the 1950s to improve patient outcome. Early devices, including hemodialysis, hemofiltration, exchange transfusion, plasmapheresis, hemoperfusion, plasma and cross-hemodialysis or cross-circulation, appeared inefficient. Meanwhile, documented results of extracorporeal liver perfusion (ECLP) suggested its superiority over conventional treatment. These devices were abandoned with the development of liver transplantation (LT), which allowed a better outcome and longer survival rate. In the present day, the fact that patients die while waiting for LT because of organ shortage led to a renewed interest in liver support as bridge to LT or regeneration. These devices can be classified according to the presence or lack of hepatocytes, whereas biologic devices refers to the presence of cells or other organic and biochemical component. The absence of individual success of early models led to the development of combined hepatocyte free devices, or artificial liver, which are based upon the hemodiabsorption principle (Biologic-DT) or on the albumin bound toxin hypothesis (Molecular Adsorbents Recirculating System) with encouraging results. Meanwhile, hepatocyte based bioartificial liver devices (BLD) were conceived for a global metabolic support. BLD were developed with the use of human hepatoma cell line (C3A) or primary or cryopreserved porcine hepatocytes. Preliminary experience gave promising results bridging patients to LT. Based upon the same principle of global hepatocyte metabolic support, ECLP regained interest, particularly with the development of transgenic pigs. Several concerns were raised about these devices. Artificial livers lacked any metabolic synthetic activity, the use of human liver for ECLP seems hardly acceptable because of organ shortage, and the accepted use of borderline livers for transplantation is pending trials for the use of xenogenic livers. For BLD, the concerns were the low hepatocyte mass, the absence of accessory liver cells, and the potential risk of seeding tumor cells into patient with the use of human hepatoma cell line. The use of porcine hepatocytes (BLD or ECLP) raised physiologic and immunologic concerns and particularly the fear of a possible transfer of porcine viral material. Although recent studies clearly demonstrate clinical improvement of patients with the use of recently developed liver support devices, most of reported prospective, controlled, or randomized trials had a small number of patients. To give the deciding vote and avoid previous pitfalls, trials need to be developed with a larger number of patients based upon statistically significant models with the following characteristics: 1) comprehensive understanding of the acute liver cell failure mechanisms, 2) world wide classification of conditions that require liver support, and 3) a clear definition of treatment success pending patients to LT or recovery without transplantation. There has not yet been conclusive evidence to support the benefits of extracorporeal liver support. We are still waiting for the deciding vote.