title: Reduced encephalopathy in pigs with ischemia-induced acute hepatic failure treated with a bioartificial liver containing alginate-entrapped hepatocytes.
abstract: OBJECTIVE
  To analyze the effects of an extracorporeal bioartificial liver containing alginate bead-entrapped hepatocytes on pigs with ischemia-induced acute hepatic failure.
  
  
  METHODS
  Prospective animal study.
  
  
  METHODS
  University and INSERM laboratory.
  
  
  METHODS
  Fifteen Large White/Pietrin female pigs weighing 20-30 kg.
  
  
  METHODS
  Acute hepatic failure was induced by end-to-side portocaval shunt and ligature of the whole porta hepatitis. The bioartificial liver was in a thermostabilized column, containing a fluidized bed of alginate beads that embedded porcine hepatocytes, connected to a plasmapheresis system. Intracranial pressure; survival; ammonia, total bilirubin, aminotransferases, alkaline phosphatase, and lactate concentrations; and clotting factors were studied. The groups were pigs with acute hepatic failure (group 1, n = 4), pigs with acute hepatic failure treated with bioartificial liver containing empty beads (group 2, n = 4), or porcine hepatocytes (group 3, n = 5).
  
  
  RESULTS
  In group 1, survival of pigs averaged 10.9 +/- 1.0 hrs; intracranial pressure reached 32.3 +/- 3.8 mm Hg and was associated with coma and cerebral edema. After connection to the bioartificial liver, the survival of acute hepatic failure pigs was 12.1 +/- 1.4 hrs in group 2 and 14.8 +/- 2.5 hrs in group 3. In group 3, intracranial pressure and bilirubin concentrations were reduced significantly compared with both group 1 and group 2. Neither signs of encephalopathy nor cerebral edema was observed in any animal of group 3. In all animals, plasma ammonium, aminotransferases, alkaline phosphatase, and lactate concentrations increased and clotting factors decreased with no significant differences between the three groups. Autopsy revealed a total necrosis of the liver, which was histologically confirmed.
  
  
  CONCLUSIONS
  The ischemia-induced model of acute hepatic failure in pigs is reproducible and provides measurable clinical and biological features. A bioartificial liver containing alginate bead-entrapped hepatocytes improves the signs of encephalopathy in pigs with ischemia-induced acute hepatic failure, suggesting that the bioartificial liver can clear out toxic compounds that are released from necrotic livers.
authors: Institut National de la Santé et de La Recherche Mèdicale Unit 456, Détoxication et Réparation Tissulaire, Hôpital Pontchaillou, Rennes, France.
authors: Mireille
authors: M
authors: Desille
authors: Stephan
authors: S
authors: Mahler
authors: Philippe
authors: P
authors: Seguin
authors: Yannick
authors: Y
authors: Mallédant
authors: Benjamin
authors: B
authors: Frémond
authors: Véronique
authors: V
authors: Sébille
authors: Anne
authors: A
authors: Bouix
authors: Jean-François
authors: JF
authors: Desjardins
authors: Agnès
authors: A
authors: Joly
authors: Jeanne
authors: J
authors: Desbois
authors: Yves
authors: Y
authors: Lebreton
authors: Jean-Pierre
authors: JP
authors: Campion
authors: Bruno
authors: B
authors: Clément
mesh_terms: D000464:Alginates; D000641:Ammonia / Q000097:blood; D000818:Animals; D005260:Female; D006501:Hepatic Encephalopathy / Q000517:prevention & control; D022781:Hepatocytes / Q000502:physiology*; D007427:Intracranial Pressure; D017093:Liver Failure / Q000628:therapy*; D019164:Liver, Artificial; D013552:Swine
chemical_list: D000464:Alginates; D000641:Ammonia