Physicians at the University of Chicago Hospitals are beginning clinical testing of the first artificial liver device that uses cells from humans rather than from pigs. The ELAD (Extracorporeal Liver Assist Device), produced by VitaGen Incorporated of La Jolla, California, is designed to serve as a temporary liver for patients with acute liver failure, keeping them alive until their own organ can recover or until a suitable organ becomes available for transplantation.
As the pilot center for the first controlled trial of the device, the University of Chicago is the only hospital in the world currently able to offer this treatment. This study will determine the safety and efficacy of the device.
"Several previous devices containing liver cells from pigs have produced encouraging results," said Michael Millis, M.D., associate professor of surgery and director of the liver transplant program at the University of Chicago Hospitals, "but there has been a good deal of concern about exposing patients to animal cells, which may function slightly differently and could harbor infectious agents. This trial should determine whether a device that incorporates human rather than pig-liver cells can reduce those risks and perhaps function more like a normal human organ."
A second advantage is that this device can be used continuously by changing the cartridges every few hours. The artifical liver devices containing pig cells can be used for no more than six to eight hours each day.
The study will involve patients with fulminant hepatic failure (FHF), a rapidly worsening liver dysfunction that primarily occurs in young, healthy people. Although the cause is often unknown, FHF can result from viral liver infections, exposure to particular toxins, or to certain drugs, such as an overdose of acetaminophen. FHF can cause multi-organ failure, brain damage and death. The natural history of this disease -- from normal health, to early symptoms such as jaundice and fatigue, to coma and death -- is often measured in days, at most a few weeks.
The primary goal of the artificial liver is to support the patient through a brief period of liver failure, protecting the brain and other organs for up to ten days, and giving the damaged liver time to recover without transplantation. In some studies, nearly two thirds of acetaminophen-damaged livers have recovered without transplantation.
The secondary goal is to extend the patient's ability to wait for a suitable organ for transplant. Patients in complete liver failure have only a few days to wait before irreversible damage begins. With more than 12,000 people currently waiting for a liver transplant and fewer than 4,500 viable livers donated each year, there is no guarantee that a suitable organ will become available in time. In 1997, 1,131 patients died while waiting for a liver transplant.
The artificial liver may also be used to support a patient after transplantation until the grafted liver begins functioning adequately and can fully sustain the patient.
"This device has the potential to reduce the need for liver transplants by giving acutely ill patients with limited liver damage time to recover," said Millis. "It could also open the window of opportunity a little wider for those who absolutely need a new organ to survive."
The portable device uses a two-chambered, hollow-fiber cartridge filled with immortalized liver cells. The cell-filled cartridges, which can be installed in a standard kidney-dialysis machine, are stored at the Vitagen laboratory in San Diego. They will be flown to Chicago -- chilled to four degrees centigrade (about 40° Fahrenheit) like a regular organ -- within hours of the request.
When attached to blood vessels in the groin, the device separates the plasma from the cellular components of the blood and pumps the patient's plasma through the filter cartridges. These cartridges bring the plasma in contact with millions of metabolically active liver cells which should function much like a normal liver. The treated plasma is then filtered, re-mixed with the cellular components of the blood, and returned to the patient.
Used cartridges will be returned to Vitagen for analysis.
Two previous uncontrolled trials, one in the United States and one in the United Kingdom, demonstrated the safety of an earlier version of this approach. The newer device has been enhanced to increase the liver cell mass and improve cell viability.
The trial will involve 24 patients. The first six to enter the study will receive standard therapy plus treatment with the ELAD. The next 18 patients will be divided randomly, nine to receive the treatment and nine to receive standard therapy.
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