Analysis: Injected Cells Zap Liver Failure

By ED SUSMAN

For many patients who go into acute liver failure — often due to ingestion of toxic substances — doctors can do little but hope the remarkable regenerative powers of the organ snap back to work before the patient dies.

In 30 percent to 70 percent of the cases, the patients die, said Vincent Arroyo Perez, head of the the digestive diseases clinic at the University of Barcelona. That’s why we are so excited about this new therapy.

Perez said he is working with researchers at Cytonet, a biotechnology company based in Weinheim, Germany, that is developing the use of human liver cells to provide a bridge to recovery for patients who develop acute liver failure.

Acute liver failure is a frustrating disease, Antonio Mas-Ordeig, head of the intensive care unit at the Barcelona clinic, told United Press International. We know that if we can just get the patient through this crisis, the liver will recover and they can have a normal life. Right now, the best chance a person in acute liver failure has is a liver transplant — and that entails a lifetime of medical treatment.

In a press briefing conducted in conjunction with the 42nd annual meeting of the European Association for the Study of the Liver, researchers described Cytonet’s plans to begin a randomized clinical trial of its human cell product.

We collect discarded liver organs, organs that have too much fat or are damaged or, for some reason, the surgeon doesn’t like the way the liver looks and won’t use it in organ transplantation, Wolfgang Rudinger, managing director of Cytonet, told UPI. We isolate viable cells and then grow them in the laboratory. The cells are frozen so we can ship them where they are needed when a patient goes into acute liver failure.

Arroyo said acute liver failure occurs infrequently, but often enough that most liver specialists have to deal with cases several times during a year. Why people go into liver failure often has to deal with drug overdose, but the cases vary widely geographically.

In the United Kingdom, about 70 percent of acute liver failure is due to acetaminophen — including Tylenol — overdoses. It’s about 20 percent of the cases in the United States, but only 2 percent of the cases in Spain, he said. Mushroom poisoning can cause acute liver failure, and it can also strike newborns with genetic defects, as well as older individuals with chronic liver disease who suddenly go into liver failure. In many cases, these patients are ineligible for organ transplant.

When we give these patients human liver cells, we also give them immunosuppressive drugs such as cyclosporine, said Michael Manns, director of gastroenterology, hepatology and endocrinology at the Center for Internal Medicine in Hannover, Germany.

When the implanted cells are in the failing liver, they take over the function of the liver and give the organ time to recover. Once the liver resumes working on its own, we can withdraw the immunosuppressants. That’s a major difference between this system and transplantation where patients are on life-long medication, Manns told UPI.

Cytonet’s Rudinger said 30 patients will be injected with the cells in the clinical trial to be conducted in 22 centers around Europe. Rudinger said the patients in acute liver failure will be treated with the human liver cells developed in facilities in Germany and at a plant in Durham, N.C., run by Vesta Therapeutics, another biotech company working with Cytonet.

The outcomes of those 30 patients will be compared with another 30 patients who will receive standard of care without the cells. The primary outcome is survival at 2 months, Rudinger said. We expect to start the trial this summer and we think we can complete it within one to two years.

The patients in the trial will not be eligible for transplantation. These trials will use the cells as a bridge to recovery, said Arroyo. "If they prove successful, we may be able to expand their use as a bridge to transplant in patients whose livers are dying.

The product has already been used in two infants and a few adults in acute liver failure, Rudinger said. But these anecdotal cases are not sufficient evidence of whether the patients who did survive would have survived without the cells.

Manns said that, in one case, a 65-year-old woman was treated with the cells after experiencing acute liver failure due to ingesting mushroom toxin. She was treated with one dose of cells, six infusions into the blood vessels that lead to the liver in an 8-hour period.

A few days later, she was able to walk out of the hospital where she had been at death’s door the previous week.

But again, this is just an anecdote, Manns said. We don’t know if she would have recovered had we done nothing. We won’t know if this treatment is real until we do the trials.

Rudinger said a second trial in children is also planned by Cytonet, which was spun off from Roche in 2000.

Commenting on the project, Xavier Forns, senior specialist in liver diseases at Hospital Clinic Barcelona, told UPI, This is a promising idea. The use of healthy liver cells to do the work on the organ as a bridge to recovery has been tried before in various ways, but none have been adopted.

Forns said about 1 percent to 5 percent of liver transplantation procedures are performed because patients are suffering acute liver failure.