Author: John C. Martin
Author Date: 3/17/2003
People diagnosed with acute liver failure have only a slim chance of
recovery or survival. But a technology in the form of an artificial
liver may be the answer for end-stage patients who face no other
option but a liver transplant, and who must wait months or even
years for a compatible donor organ.

This novel bio-artificial technology is known simply as ELAD, which
stands for extracorporeal liver device, developed by VitaGen of La
Jolla, California. It is the first such technology to contain
functioning human hepatocytes-liver cells-which help sustain and
support the intensive work of the patients damaged and failed organ.
This is the first liver assist system, ELADs designers contend, that
uses liver cells from humans rather than pigs.

"This device could serve as a bridge to successful transplantation,
helping to sustain patients awaiting a donor organ," said Roshan
Shrestha, M.D., an associate professor of medicine at the University
of North Carolina, one of a handful of medical institutions around
the country where the device is about to face a battery of clinical
tests.

Acute Liver Failure
Acute liver failure is a potentially deadly condition that affects
about 2000 Americans each year. In most cases, liver failure
develops over a period of years as the culmination of a series of
insults to the liver, such as hepatitis virus infection or alcohol
abuse. Conversely, acute liver failure can progress in only a matter
of days or weeks.(1)

The new ELAD device is a closed system that tethers patients by way
of a catheter inserted into a vein in the neck. After the blood is
initially filtered, the remaining plasma is funneled through
cartridges in the device where human liver cells help fulfill much
of the livers 100 or so crucial functions, such as energy storage
and regulation, bile production, blood detoxification, and the
production of clotting factors and many essential proteins.

The filtered blood and ELAD-treated plasma are then returned to the
patient.

"A remarkable feature of the liver is its capacity to regenerate,"
Shrestha explained. "If we can sustain acute liver failure patients
early on, right from the beginning, they may not need
transplantation and may recover without any significant liver
problems, including chronic liver disease."

ELAD Passes Muster
While ELAD still awaits FDA approval, Shrestha said an initial phase
clinical trial conducted in the United States and Great Britain
several years ago showed promising results. In that baseline trial,
nearly 92 percent of patients who had been selected at random to
receive treatment with the ELAD achieved either a successful bridge
to transplantation or full recovery, the authors reported.

In a comparative control group of patients receiving standard care,
the researchers reported that only 42 percent achieved the same
benefits.

In an analysis of overall results in 25 patients, including those
not listed for transplantation, 81 percent improved on the device,
compared to only about half of those patients in the control group.

More Trials Planned
Shrestha pointed out that the FDA was sufficiently pleased with the
results of the early-stage trial to prompt a subsequent clinical
trial to test ELADs safety and effectiveness.

"The primary objective is to evaluate the safety, efficacy and
tolerability of the ELAD system in patients with acute hepatic
failure," he said. "Our secondary objective is to evaluate the study
protocol with respect to patient inclusion and exclusion criteria,
and to study the systems performance with regard to endpoints."

Currently, 30 to 40 patients are scheduled to be enrolled. If
successful, a third phase clinical trial may be launched involving
larger numbers of patients.

Shrestha commented: "Currently, we dont have very good therapies for
patients with acute liver failure. Thats why were hoping that the
new technology will make a big difference. The bottom line is to
save lives."

1. American College of Physicians. American Society of Internal
Medicine. Acute Liver Failure in the United States. 2002.

John Martin is a long-time health journalist and an editor for
Priority Healthcare. His credits include coverage of health news for
the website of Fox Television's The Health Network, and articles for
the New York Post and other consumer and trade publications.