Results of a phase I trial evaluating a liver support device utilizing albumin dialysis

Abstract

Background: We have previously reported the clearance of protein-bound and water-soluble hepatic toxins, in vitro and in an animal model, using albumin dialysis as an extracorporeal hepatic support (ECHS) device.

Objective: The objective of this study was to evaluate albumin dialysis through a phase I clinical trial. We hypothesized that albumin dialysis would (1) decrease elevated levels of hepatic toxins, (2) increase the Fischer ratio, and (3) decrease hepatic encephalopathy (HES) and intracranial pressure (ICP), while (4) maintaining stable hemodynamics.

Methods: Patients with acute liver failure were treated with an ECHS device utilizing continuous hemodiafiltration with continuous albumin dialysis. Mean arterial blood pressure (MAP), heart rate (HR), systemic venous oxygen saturation (Svo(2)), ICP, and HES were recorded. Blood samples were evaluated for hepatic toxins and factor VII levels.

Results: Nine patients were enrolled (status I, n = 5; status IIA, n = 4). There was no significant change in MAP, HR, or Svo(2) (MAP: Pre = 81 +/- 5.6 mm Hg, Post = 79 +/- 5.9 mm Hg, P =.70; HR: Pre = 104 +/- 5.2 bpm, Post = 107 +/- 6.2 bpm, P =.62; Svo(2): Pre = 72 +/- 3.5, Post = 71 +/- 1.7, P =.77). There was a decrease in the ammonia and total bilirubin levels (NH(3): Pre = 129.8 +/- 23.8 mg/dL, Post = 63.9 +/- 16.1 mg/dL, P =.01; total bilirubin: Pre = 20.3 +/- 2.5 mg/dL, Post = 17.6 +/- 2.7 mg/dL, P =.4). There was a significant increase of the Fischer ratio and factor VII levels (Fischer ratio: Pre = 0.98 +/- 0.2, Post = 2.17 +/- 0.5, P =.038; factor VII: Pre = 13.9 +/- 4.9, Post = 23.2 +/- 4.8, P =.015). There was a significant decrease in the HES and ICP (HES: Pre = 3.8 +/- 0.1, Post = 2 +/- 0.7, P =.02; ICP: Pre = 37 +/- 3.9, Post = 13.3 +/- 2.8, P =.048). Of 5 status I patients, 1 recovered native hepatic function and 3 were bridged to transplantation.

Conclusions: This phase I study suggests that albumin dialysis as a liver support device is safe and effective in clearing hepatic toxins, with an associated decrease in the HES and ICP. This encouraging efficacy data warrant further investigation with a phase II/III trial.