Treatment of acute liver failure in pigs reduces hepatocyte function in a bioartificial liver support system.
Several different types of bioartificial liver (BAL) support systems have been developed to bridge patients suffering from acute liver failure (ALF) to transplantation or liver regeneration. In this study we assessed the effects of ALF plasma on hepatocyte function in the BAL system that has been developed in our center. Pigs (40-60 kg) were anaesthetised and a total hepatectomy was performed. Cells were isolated from the resected livers and were transferred to the bioreactor of the BAL system. Twenty hours after cell isolation, hepatocytes in the BAL were tested for cell viability and functional activity by using a recirculating test medium in which assessment of LDH leakage, ammonia clearance, urea synthesis, 7-ethoxycoumarin O-deethylase (ECOD) activity and pseudocholine esterase production was performed. Subsequently, two groups were studied. In one group (I, n=5), the cell-loaded bioreactor was used to treat the donor pig, rendered anhepatic, for 24 hours. In the second group (II, n=5) the bioreactor was cultured for 24 h and served as a control. After 24 hours treatment or culturing, the cell viability count and functional activity tests were repeated. The results show that hepatocytes in the BAL remained viable after 24 h treatment of anhepatic pigs, as shown by the LDH release and pseudocholine esterase production. However, metabolic functions such as ammonia clearance, ECOD and urea synthesis were reduced after 24 h exposure of hepatocytes to autologous ALF plasma, whereas these functions were unaltered after 24 h culturing of the cells in the bioreactor.
Abrahamse
S L
SL
Department of Surgery, Academic Medical Center, The University of Amsterdam, Amsterdam, The Netherlands.
van de Kerkhove
M P
MP
Sosef
M N
MN
Hartman
R
R
Chamuleau
R A F M
RA
van Gulik
T M
TM
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017114:Liver Failure, Acute / Q000378:metabolism / Q000628:therapy*; D019164:Liver, Artificial; D013552:Swine; D014508:Urea / Q000378:metabolism
D000641:Ammonia; D014508:Urea; D007770:L-Lactate Dehydrogenase; D015660:7-Alkoxycoumarin O-Dealkylase; D002091:Butyrylcholinesterase