title: Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver.
abstract: Aim of the study was to evaluate treatment efficacy and safety of a scaled-up version of our porcine hepatocytes based BAL system in pigs with complete liver ischemia (LIS). Thirty-one pigs underwent total devascularization of the liver (LIS) by termino-lateral porta-caval shunts and sutures around the bile duct, the common hepatic and gastroduodenal arteries and their accessory branches. The hepato-duodenal ligament was completely transected. Four experimental groups were studied: the first control group (LIS Control, n = 10) received glucose infusion only, the second control group (LIS Plasmapheresis, n = 8) was connected to a centrifugal plasma-separator with a bottle representing the bioreactor volume, the third control group (LIS Empty-BAL, n = 5) received BAL treatment without cells, and the treated group (LIS Cell-BAL, n = 8) was connected for a maximum period of 24 hours to our scaled-up BAL seeded with around 14 billion viable primary porcine hepatocytes. BAL treatment significantly prolonged life in large animals (approximately 35 kg) with complete LIS (Controls, mean +/- SEM: 33.1 +/- 3 h, Cell-BAL: 51.1 +/- 3.4 h; p = 0.001; longest survivor 63 h). In addition, blood ammonia and total bilirubin levels decreased significantly, indicating metabolic activity of porcine hepatocytes in the bioreactor. No significant differences were noticed among the three control groups, indicating that there was no device effect and that the plasmapheresis procedure was well tolerated. No important adverse effects were observed.
authors.affiliation: Department of Experimental Internal Medicine, University of Amsterdam, Academic Medical Center, The Netherlands.
authors.forename: L M
authors.initials: LM
authors.lastname: Flendrig
authors.forename: F
authors.initials: F
authors.lastname: Calise
authors.forename: E
authors.initials: E
authors.lastname: Di Florio
authors.forename: A
authors.initials: A
authors.lastname: Mancini
authors.forename: A
authors.initials: A
authors.lastname: Ceriello
authors.forename: W
authors.initials: W
authors.lastname: Santaniello
authors.forename: E
authors.initials: E
authors.lastname: Mezza
authors.forename: F
authors.initials: F
authors.lastname: Sicoli
authors.forename: G
authors.initials: G
authors.lastname: Belleza
authors.forename: A
authors.initials: A
authors.lastname: Bracco
authors.forename: S
authors.initials: S
authors.lastname: Cozzolino
authors.forename: D
authors.initials: D
authors.lastname: Scala
authors.forename: M
authors.initials: M
authors.lastname: Mazzone
authors.forename: M
authors.initials: M
authors.lastname: Fattore
authors.forename: E
authors.initials: E
authors.lastname: Gonzales
authors.forename: R A
authors.initials: RA
authors.lastname: Chamuleau
mesh_terms: D000818:Animals; D001711:Biotransformation; D004195:Disease Models, Animal; D008099:Liver / Q000166:cytology*; D017114:Liver Failure, Acute / Q000628:therapy*; D008111:Liver Function Tests; D019164:Liver, Artificial; D008297:Male; D010956:Plasmapheresis / Q000379:methods; D012016:Reference Values; D015996:Survival Rate; D013552:Swine; D016896:Treatment Outcome