Reduced encephalopathy in pigs with ischemia-induced acute hepatic failure treated with a bioartificial liver containing alginate-entrapped hepatocytes.
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.
Desille
Mireille
M
Institut National de la Santé et de La Recherche Mèdicale Unit 456, Détoxication et Réparation Tissulaire, Hôpital Pontchaillou, Rennes, France.
Mahler
Stephan
S
Seguin
Philippe
P
Mallédant
Yannick
Y
Frémond
Benjamin
B
Sébille
Véronique
V
Bouix
Anne
A
Desjardins
Jean-François
JF
Joly
Agnès
A
Desbois
Jeanne
J
Lebreton
Yves
Y
Campion
Jean-Pierre
JP
Clément
Bruno
B
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
D000464:Alginates; D000641:Ammonia