PRECLINICAL TRIAL OF A BIOARTIFICIAL LIVER SUPPORT SYSTEM IN A PORCINE FULMINANT HEPATIC-FAILURE MODEL

Background: This study describes: the pre-clinical trials of an extrac orporeal bioartificial liver support system (BALSS). It includes the b iochemical changes which occur in the plasma and blood of pigs with de vascularized livers when the plasma is treated in a BALSS, and the tes ting of the system for presence or absence of infective agents, pyroge ns and for toxicity. Methods: Hepatic cells were prepared from litterm ate juvenile white landrace pigs with a double-step collagenase digest technique. The cell preparations were incubated with collagen-coated dextran microspheres (CDM) for 3 h and the medium was tested to determ ine cellular metabolic activity. Incubation continued for a further 20 h during which the hepatic cells attach to the CDM. The CDM-attached cells were inoculated into a hollow fibre bioreactor which was part of an extracorporeal liver support system. Results: Hepatic cell content of the bioreactor was 6 x 10(9) +/- 3 x 10(8) cells, equivalent to th ose present in half a pig's liver. The system was tested in a controll ed trial with the plasma of pigs with fulminant hepatic failure (FHF) due to devascularized livers. When plasma from FHF pigs was circulated through the device there was significantly less of an increase in the accumulation of ammonia, lactate and most amino acids when hepatic ce lls were included in the circuit compared with those in control experi ments when they were excluded. Similar changes occurred in porcine blo od. There were few infections diagnosed and an absence of pyrogens, en dotoxins and toxicity in the bioreactor contents or in the terminating reservoir or animal blood samples. Conclusions: We believe that the r esults, demonstrating function of the porcine hepatic cells in the cir cuit, together with low risks, justify a clinical trial of use of the BALSS in Australia.