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. DESIGN: Prospective animal study. SETTING: University and INSERM laboratory. SUBJECTS: Fifteen Large White/Pietrin female pigs weighing 20-30 kg. INTERVENTIONS: 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). MEASUREMENTS AND MAIN 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.