title: Preclinical trial of a bioartificial liver support system in a porcine fulminant hepatic failure model.
abstract: BACKGROUND
  This study describes the pre-clinical trials of an extracorporeal bioartificial liver support system (BALSS). It includes the biochemical changes which occur in the plasma and blood of pigs with devascularized livers when the plasma is treated in a BALSS, and the testing of the system for presence or absence of infective agents, pyrogens and for toxicity.
  
  
  METHODS
  Hepatic cells were prepared from littermate 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 determine 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 those present in half a pig's liver. The system was tested in a controlled 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 cells were included in the circuit compared with those in control experiments when they were excluded. Similar changes occurred in procine blood. There were few infections diagnosed and an absence of pyrogens, endotoxins and toxicity in the bioreactor contents or in the terminating reservoir or animal blood samples.
  
  
  CONCLUSIONS
  We believe that the results, demonstrating function of the porcine hepatic cells in the circuit, together with low risks, justify a clinical trial of use of the BALSS in Australia.
authors.affiliation: Australian National Liver Transplantation Unit, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
authors.forename: A G
authors.initials: AG
authors.lastname: Sheil
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: D C
authors.initials: DC
authors.lastname: Mears
authors.forename: M
authors.initials: M
authors.lastname: Waring
authors.forename: K
authors.initials: K
authors.lastname: Woodman
authors.forename: B
authors.initials: B
authors.lastname: Johnston
authors.forename: M
authors.initials: M
authors.lastname: Horvat
authors.forename: K J
authors.initials: KJ
authors.lastname: Watson
authors.forename: N
authors.initials: N
authors.lastname: Koutalistras
authors.forename: L S
authors.initials: LS
authors.lastname: Wang
mesh_terms: D000596:Amino Acids / Q000032:analysis; D000641:Ammonia / Q000032:analysis; D000818:Animals; D001187:Artificial Organs; D005112:Extracorporeal Circulation; D005340:Fibrinogen / Q000032:analysis; D006501:Hepatic Encephalopathy / Q000628:therapy*; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D008099:Liver / Q000166:cytology*; D013552:Swine
chemical_list: D000596:Amino Acids; D007773:Lactates; D019344:Lactic Acid; D000641:Ammonia; D005340:Fibrinogen