Preclinical evaluation of the Excorp Medical, Inc, Bioartificial Liver Support System.

BACKGROUND

Acute liver failure has no medically recognized effective therapy other than orthotopic liver transplantation. Development of bioartificial livers for support of patients with acute liver failure requires meaningful preclinical evaluation before clinical trials.

STUDY DESIGN

Complete results from preclinical safety and efficacy evaluation of the Excorp Medical Bioartificial Liver Support System (BLSS) using a D-galactosamine (D-gal) canine liver failure model are presented. From a total cohort of 23 purpose-bred male hounds, 18 animals were administered a lethal dose (1.5 g/kg) of D-gal. The 18 animals were divided into four treatment groups: no BLSS treatment (n = 6), BLSS treatment starting at 24 to 26 hours post D-gal (n = 5), BLSS treatment starting at 16 to 18 hours post D-gal (n = 4), and "mock support" treatment with a BLSS system containing no hepatocytes (n = 3). The animals were treated until death or death equivalent, or euthanized at 60 hours. Physiologic parameters were continuously monitored. Blood chemistries were obtained every 8 hours.

RESULTS

Although survival times for BLSS-supported animals were significantly greater than for the unsupported group, the greatest impact on delaying progression of liver disease was time of intervention. Intervention at 16 to 18 hours post D-gal administration showed significant delay in increasing blood ammonia, lactate, and prothrombin time as compared with untreated animals. Elevated intracranial pressure was found in two of six untreated animals, but in none of the treated animals (zero of nine). Healthy animals supported by the BLSS system evidenced no significant safety problems.

CONCLUSIONS

Results suggest the BLSS impacts the course of liver failure in the animal model. Phase I clinical safety evaluation is underway.