Evaluation of a Non-Cell Based Extracorporeal Liver Support Device in an Animal Model of Hepatic Failure

Background: Clearance of toxins, that have been implicated as a cause of hepatic encephalopathy and cerebral edema, has been proven effective in vitro, using a non-cell based extracorporeal liver support device (ECHS), which utilizes hemodiafiltration with an albumin dialysate.

Objective: To evaluate the safety and efficacy of ECHS in an animal model of hepatic failure prior to clinical trials. Our hypothesis was that continuous veno-venous hemodiafiltration with albumin dialysis would: 1) decrease elevated levels of total bilirubin and ammonia, 2) reverse the ratio of branched chain to aromatic amino acids (Fischer ratio), and 3) maintain stable blood pressure and heart rate.

Methods: Seventeen mongrel dogs underwent common bile duct ligation and an end-to-side portocaval shunt. On postoperative day 7, with continuous monitoring of blood pressure and heart rate, 9 of 17 dogs (Group A) underwent continuous hemodiafiltration (Blood Flow rate = 11.8 cc/kg/min) for six hours using a 10 % albumin solution as the recirculated dialysate which passes through an activated charcoal sorbent column (Dialysate Flow rate = 11.8 cc/kg/min). Blood samples were collected before and after treatment and evaluated for total bilirubin, ammonia, aromatic and branched chain amino acids. The remaining 8 untreated dogs served as non-treatment controls (Group B). Comparisons were made using ANOVA and paired Student’s t test.

Results: All nine animals in group A survived ECHS treatment with stable hemodynamics. The total bilirubin, and ammonia concentrations significantly decreased from 4.7 ± 2.3 to 3.1 ± 1.6 mg/dl (p = 0.001), and 204 ± 105 to 142 ± 89 mg/dl (p = 0.001) respectively, while the Fischer ratio significantly increased by 25 % from 1.72 ± 0.38 to 2.15 ± 0.36 (p = 0.002). The eight untreated dogs continued to have significantly elevated bilirubin and ammonia concentrations and a significantly decreased Fischer ratio as compared to baseline.

Conclusion: An extracorporeal liver assist device which utilizes selective hemodiafiltration with albumin dialysis is effective in clearing ammonia, aromatic amino acids, and bilirubin in an animal model of hepatic failure, without any adverse hemodynamic effects.