Biomedical Engineering Reference
In-Depth Information
It is unlikely that the complex mechanism, by which the liver ensures
homeostasis, can be replaced by means of nonbiologic detoxification alone. A
bioartificial liver, which incorporates hepatocytes from various sources, has the
theoretical advantage of not only providing blood purification through dialysis, but
also providing the hepatocyte-specific functions which are lost with ALF. The first
biologically based liver assist device to be tested in FDA-approved phase II/III
trial was HepatAssist
TM
by Arbios (formerly Circe, Waltham, MA). The device
employed a hollow fiber extracorporeal bioreactor loaded with cryopreserved
primary porcine hepatocytes. A randomized, controlled, multicenter phase II/III
clinical trial was conducted in patients with fulminant/subfulminant liver failure
and primary graft nonfunction [
69
]. The study demonstrated favorable safety, but
failed to demonstrate improved 30-day survival in the overall study population.
Although subgroups of the study population showed significant survival benefits,
HepatAssist is not yet approved by the FDA. The extracorporeal liver assist device
(ELAD
TM
) developed by Vital Therapies (San Diego, CA) utilizes hollow fiber
cartridges loaded with cells from the C3A human hepatoblastoma cell line. The
most current model also contains a conventional hemodialysis unit. An early
randomized controlled trial of 24 patients with acute alcoholic hepatitis demon-
strated that therapy with ELAD produced reduced levels of ammonia and bilirubin
along with improvement in hepatic encephalopathy when compared to controls
[
70
]. However, a statistically significant survival advantage was not demonstrated.
The modular extracorporeal liver support system (MELS
TM
; Charité, Berlin,
Germany) is a hepatocyte based liver support therapy composed of four inde-
pendently functioning hollow fiber capillary cell compartments. A phase I study in
2003 including eight patients with ALF demonstrated safety, with all eight patients
being successfully bridged to transplantation [
71
]. Clinical experience with MELS
has been limited by the infrequent and unpredictable supply of human hepatocytes
and concerns of xenozoonosis involving pig hepatocytes which are prevalent in
Europe. The bioartificial liver support system (BLSS
TM
) by Excorp medical
(Minneapolis, MN,U.S.A) is a system that utilizes *100 g of primary porcine
hepatocytes in a single hollow fiber cartridge. Venovenous bypass is used to
circulate the patient's blood through the system. A phase I trial, in which four
patients were treated with BLSS, demonstrated safety [
72
]. Currently, a phase II/
III study is underway, and results will further define the role of this device. The
Amsterdam medical Center bioartificial liver (AMC-BALTM; AMC, Amsterdam,
The Netherlands) uses 100 g of primary porcine hepatocytes bound to a spiral-
shaped polyester fabric with integrated hollow fibers. During treatment, the bio-
reactor is perfused with the patient's plasma. A phase I study of the system
examined seven patients with ALF who underwent multiple treatments with AMC-
BAL [
73
]. Six were successfully bridged to transplantation, and one patient
recovered liver function without transplantation. Improvements were observed in
both clinical and biochemical parameters including a decrease in both bilirubin
and ammonia. No adverse events were associated with treatment. While pre-
liminary results were encouraging, larger randomized, controlled trials are needed
to determine the role of AMC-BAL.
