Assessment of the AMC-bioartificial liver in the anhepatic pig

Abstract

Background: The anhepatic pig model was used to evaluate a bioartificial liver developed in our institution (AMC-BAL). The bioartificial liver is based on oxygenated plasma perfusion of porcine hepatocytes attached to a polyester matrix.

Methods: Pigs (n=15) underwent total hepatectomy with restoration of caval continuity using a polyethylene, three-way prosthesis. In group I, pigs received limited intensive care under continuation of general anesthesia (n=5). Group II pigs (n=5) underwent, in addition, extracorporeal plasma perfusion of an AMC-BAL without hepatocytes (device control group). In group III (n=5), plasma perfusion occurred with an AMC-BAL loaded with autologous hepatocytes. Groups II and III were connected to the extracorporeal system 24 hr after hepatectomy, for a period of 24 hr. The main outcome parameters were as follows: survival time, liver enzymes (aspartate aminotransferase, alanine aminotransferase), blood ammonia, and total/direct bilirubin.

Results: Survival (mean +/- SD) of the anhepatic pigs was significantly increased in the BAL-treated group (group III: 65+/-15 hr), as compared with the control groups (group I: 46+/-6 hr and group II: 43+/-14 hr). Mean blood ammonia levels during BAL treatment were significantly lower in the BAL-treated group in comparison with both control groups (P=0.02). Total and direct bilirubin levels gradually increased after hepatectomy and reached maximum values of 1.98 mg/dl and 1.50 mg/dl, respectively, showing no differences between the three groups.

Conclusions: (1) Treatment of anhepatic pigs with the AMC-BAL containing autologous hepatocytes significantly increases survival time, which is associated with a significant decrease in blood ammonia. 2) Anhepatic pigs demonstrate increasing direct bilirubin levels as a result of extrahepatic bilirubin conjugation.