Significantly improved survival time in pigs with complete liver ischemia treated with a novel bioartificial liver

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 complet e liver ischemia (LIS). Thirty-one pigs underwent total devascularization of the liver (LIS) by ter mino-lateral porta-caval shunts and sutures around the bile duct, the commo n hepatic and gastroduodenal arteries and their accessory branches. The hep ato-duodenal ligament was completely transected Four experimental groups we re studied: the first control group (LIS Control, n = 10) received glucose infusion only, the second control group (LIS Plasmapheresis, n = 8) was con nected to a centrifugal plasma-separator with a bottle representing the bio reactor volume, the third control group (LIS Empty-DAL, n = 5) received BAL treatment without cells, and the treated group (LIS Cell-DAL, n = 8) was c onnected 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 (similar to 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 ac tivity 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 i mportant adverse effectes were observed.