Development and perspectives of bioartificial liver support.

Bioartificial liver support systems containing adsorbent devices, xenogeneic whole liver perfusion, and hybrid bioartificial liver are anticipated to be effective for the treatment of severe hepatic failure. At present, whole liver perfusion and the hybrid bioartificial liver are two mainstreams in the field of the bioartificial liver, but it is still unclear whether either of them has significant beneficial effects in hepatic failure patients. We developed a new system of xenogeneic direct hemoperfusion consisting of a leukocyte adsorbent, an immunoglobulin adsorbent, and a substitute unit for hepatic function, that is, whole liver or bioreactor. Using this system, the perfusion efficiency rate and oxygen supply of the substitute unit for hepatic function were significantly increased. A further improvement of our system by incorporating a leukocytapheresis device to return the leukocyte-rich portion of the perfused blood back to the patient's body directly was undergone. Moreover, our system can be applied not only as a bioartificial liver, but also as a bioartificial kidney. To solve the problem of xenogeneic protein influx into the human body associated with extracorporeal bioartificial liver support, it is important to develop transgenic cattle in which human protein genes are transduced. Influx of porcine endogenous retrovirus into the human body has been a controversial subject. In relation to this issue, the cross-hemoperfusion method is promising in that the patient's circuit and the bioartificial liver circuit are separated by a semipermeable membrane, which can prevent any kind of virus from flowing into the patient's circuit.