PITTSBURGH, Dec. 21 -- Researchers at the University of Pittsburgh Medical Center (UPMC) have begun testing a new bioartificial liver assist system designed by Excorp Medical, Inc., that uses healthy liver cells from pigs as a means to improve the liver function of critically ill patients with liver failure. The trial is intended to assess the safety of the system, but researchers also will be paying close attention to whether it can improve a patient's condition until transplantation is feasible or if it can obviate the need for transplantation altogether if the failing liver recovers.
"One patient has already undergone treatment without any harmful effects. This patient had multiple serious medical complications associated with liver failure as well as her underlying disease. She tolerated the treatment well, and by clinical measures, her neurological status initially improved.
Unfortunately, as is often the case with these patients, she suffered a serious setback a week later and died from an overwhelming infection," said George Mazariegos, M.D., assistant professor of surgery at the Thomas E. Starzl Transplantation Institute and co-director of the liver transplant intensive care (ICU) service at UPMC Presbyterian. Dr. Mazariegos is also co-principal investigator of the study.
"Because this is a Phase I clinical trial, we are most concerned about the safety of the system. But we'll be looking at efficacy as well. The system may benefit patients if their condition improves and they can be considered eligible for transplantation or if their liver regenerates and resumes normal function," said David J. Kramer, M.D., co-principal investigator, associate professor of anesthesiology and critical care medicine and co-director of the liver transplant ICUs with Dr. Mazariegos.
Researchers intend to study 15 patients with encephalopathy, a life-threatening complication of both chronic and acute liver failure. Because the liver is unable to function properly, toxins normally cleansed by the liver circulate in the bloodstream and to the brain. In its severest form, patients become unresponsive or comatose. Encephalopathy is one of the most common reasons liver disease patients are admitted to the intensive care unit.
Chronic liver failure occurs in patients who develop cirrhosis after many years with liver disease. Acute liver failure, also known as fulminant hepatic failure, is a more sudden assault on the liver, occurring in patients with no prior history of liver disease. These may be patients who have been poisoned by mushrooms or toxic levels of acetaminophen, or who suddenly contract a virus that attacks their liver.
For most patients with liver failure, the only treatment is liver transplantation. But not all patients are medically stable enough to be considered as candidates. And a shortage of organs means that many who are listed die without the opportunity to be transplanted. In a small percentage of cases, patients with acute liver failure can recover and do not need transplants.
Researchers will compare the outcomes of patients who receive treatments with the Excorp Medical bioartificial liver system, which takes 12 hours and may be repeated, with similar patients who receive standard intensive care treatment.
A catheter connects a patient to the system, which remains outside the body, and treats blood that passes through a cylinder filled with hollow polymer fibers and a suspension containing billions of pig liver cells. The fibers act as a barrier to prevent proteins and cell byproducts of the pig cells from coming in direct contact with the patient's blood but allow the necessary contact between the cells so that the toxins in the blood can be removed.
"There are, as yet, no proven bioartificial therapies to treat patients with encephalopathy and liver failure. We are hopeful that careful and measured research using this system will offer some hope to the 10,000 patients waiting for liver transplants," said Daniel G. Miller, Ph.D., president and CEO of Excorp Medical.
Review by the U.S. Food and Drug Administration was necessary to assure the study uses the proper mechanisms to screen and monitor for potential animal viruses. Like all studies involving humans, the study was also reviewed and approved by the university's Institutional Review Board.
The UPMC and Minnesota-based Excorp Medical have been collaborating on the basic and animal research of the system for nearly three years. The UPMC houses one of the world's largest liver transplant programs and performs more types of transplants than any other center. It has served as a clinical testing ground for a number of artificial organ devices and is a leader in artificial organ development research. Excorp Medical, Inc., is an emerging company focused on the therapeutic application of cell-culture and bioengineering technology.
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