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Artificial Liver Trials Show Progress, As Transplant Candidates Wait

Date:
September 10, 2002
Source:
University Of Michigan Health System
Summary:
Four years after the first American clinical trial of an experimental artificial liver system began at the University of Michigan Health System, its leader says he is encouraged by the results thus far. And, he's optimistic about the system's potential to help more liver-failure patients stay alive until they receive a liver transplant, or recover without a transplant.

BERLIN – Four years after the first American clinical trial of an experimental artificial liver system began at the University of Michigan Health System, its leader says he is encouraged by the results thus far. And, he's optimistic about the system's potential to help more liver-failure patients stay alive until they receive a liver transplant, or recover without a transplant.

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Already, says Robert Bartlett, M.D., 20 desperately ill patients at the U-M Health System have used the device in a phase I trial. Six patients went on to receive a transplant, three of whom are still alive. Two other patients recovered liver function without needing a transplant. Data on the first nine U-M patients were published last August in the journal Surgery; Bartlett discussed the full group at a meeting this week in Germany.

Results from Germany, where the system was invented, and from the three other American hospitals now testing it, also give Bartlett hope. In all, the system appears safe, able to reduce blood toxins, and able to reverse coma and shock.

The system, called albumin dialysis, uses special filters and proteins to remove toxic substances from the blood while sparing helpful compounds.

Bartlett spoke about the status of the albumin dialysis approach to liver support in the keynote and summary addresses at the Fourth International Symposium on Albumin Dialysis in Liver Disease this week in Rostock, Germany.

"Current and future clinical trials will help further establish how well albumin dialysis might help buy time for the 17,400 Americans now waiting for a liver transplant, and the tens of thousands more on waiting lists worldwide," says Bartlett, who is a professor of surgery, director of critical care and head of the extracorporeal life support team at UMHS.

"We must also explore whether the system can help patients regain function in their own livers, as two of our patients did," he continues. "Currently, we are using albumin dialysis only for patients in the intensive-care unit who need emergency liver transplants, but we will soon extend the treatment to other patients with liver diseasel."

The U-M is preparing to participate in a multicenter, randomized controlled trial comparing albumin dialysis with standard medical treatment in chronic liver failure patients who are in hepatic comas -- a neurological state caused by liver failure.

The new U-M trial, led by U-M gastroenterologist Robert Fontana, M.D., will begin in early 2003. It will use the MARS, or Molecular Adsorbent Recirculating System, equipment made by the Teraklin AG company of Rostock, Germany and available in the United States under an investigational device permit from the Food and Drug Administration. The initial U-M study has used technology similar to the MARS system.

Artificial liver support is one of medicine's longest-standing challenges, with nearly 40 years of basic and clinical research producing no systems able to remove toxins, leave behind beneficial blood components, and produce positive immediate and long-term survival results.

Meanwhile, tens of thousands of Americans experience acute or chronic liver failure each year, caused by hepatitis and other infections, degenerative diseases, overdoses, and alcohol abuse.

Liver transplants offer hope for many, but there aren't enough organs from deceased and living donors to go around. In 2001, 5,177 Americans received new livers, but another 1,975 died waiting. Nearly 1,000 of the more than 17,460 patients now waiting are children and teenagers.

A new liver transplant candidate system instituted by the United Network for Organ Sharing in 2001 places the sickest patients -- called status 1 -- at the top of the list to receive livers as they become available. But that means patients are most likely to receive a liver when they have the least amount of time to wait. Status 1 patients are defined as having less than 7 days to live.

That makes artificial liver support more crucial than ever, says Bartlett.

Recently, artificial liver technology has branched into two categories: one using living pig or human liver cells, and the other using various filtering mechanisms.

"Bio-artificial livers, which use living cells, have not yet lived up to their initial promise," says Bartlett, noting that trials are continuing but research has been hampered in part by the inability to grow liver cells quickly and safely enough. "Filtering devices, on the other hand, have also failed to give consistent results and have often taken the 'good' out of the blood with the 'bad'."

The albumin dialysis approach seeks to avoid these limitations, using human albumin. In healthy people, albumin grabs toxic molecules and other substances in the blood, carrying them to the liver where they are detached and stored. But in people whose livers are failing, the toxins stay in the blood and can harm nerve function, increase pressure in the brain, and damage other important systems.

Albumin dialysis pumps the blood out of the body and into a plastic tube filled with hollow fibers made of a membrane that has been coated with albumin. On one side of the fiber's membrane is the blood; on the other, a dialysis solution containing more albumin.

The toxins on the albumin in the patient's blood are attracted to the albumin on the membrane, which is "stickier" because it has more room for molecules to attach. Then, the albumin on the membrane passes the toxins along to the albumin in the solution as it flows by.

Meanwhile, smaller toxin molecules that don't stick to albumin flow through the membrane's tiny pores into the less-concentrated dialysis solution. The patient's own albumin, too large to fit through the membrane's pores, returns to the body with the blood.

In the U-M safety trial, all patients tolerated albumin dialysis well, with no adverse mechanical or bleeding effects. Concentrations of ammonia, free fatty acids and amino acid toxins decreased significantly.

All patients had improvement in their neurological state, some had decreases in intracranial pressure, and there were some signs that the native livers were regaining the ability to produce important molecules of its own.

In all, five of the ten patients classified as status 1 are alive and well today.

Those results are similar to ones reported from trials in Germany, Denmark, Italy, Israel and other countries in recent years. The clinical literature from albumin dialysis studies was analyzed collectively by Bartlett and colleagues from the University of California San Diego and the University of Rostock in an article published in February, 2002 in the journal Artificial Organs.

Besides the U-M and UC San Diego, the other American centers testing albumin dialysis are Columbia University and Northwestern University.

Bartlett envisions a day when albumin dialysis might become a treatment for liver failure like kidney dialysis is for kidney failure -- something to do several times a week for a few hours, rather than around the clock in the intensive care unit.

"The definitive studies are being done now, and only time will tell," he says. "But we've had good success so far, and we hope to continue."

In addition to Bartlett and Fontana, other U-M researchers are Fresca Swaniker, M.D., John Magee, M.D., Jeffrey Punch, M.D. and Steve Rudich, M.D. Former U-M surgery fellow Samir Awad, M.D., now at Baylor College of Medicine in Houston, was lead author of the study published in 2001.

References:

The Molecular Adsorbents Recycling System as a Liver Support System Based on Albumin Dialysis: A Summary of Preclinical Investigations, Prospective Randomized Controlled Clinical Trials, and Clinical Experience from 19 Centers. Stange et al, Artificial Organs, 26(2):103-110

Results of a Phase I trial evaluating a liver support device utilizing albumin dialysis. Awad et al, Surgery, Vol. 130, No. 2, 354-362.


Story Source:

The above story is based on materials provided by University Of Michigan Health System. Note: Materials may be edited for content and length.


Cite This Page:

University Of Michigan Health System. "Artificial Liver Trials Show Progress, As Transplant Candidates Wait." ScienceDaily. ScienceDaily, 10 September 2002. <www.sciencedaily.com/releases/2002/09/020910080712.htm>.
University Of Michigan Health System. (2002, September 10). Artificial Liver Trials Show Progress, As Transplant Candidates Wait. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2002/09/020910080712.htm
University Of Michigan Health System. "Artificial Liver Trials Show Progress, As Transplant Candidates Wait." ScienceDaily. www.sciencedaily.com/releases/2002/09/020910080712.htm (accessed December 22, 2014).

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