With more than 17,000 people on the waiting list for a new liver — many of them getting sicker by the day — Arbios Systems (Waltham, Massachusetts) is trying to make life on the waiting list a little more bearable for those patients and provide the necessary bridge to transplant.

At the annual meeting of the American Association of Liver Disease (AASLD; Alexandria, Virginia) in Boston this past weekend, Arbiospresented data from the first five patients treated with its Sepet Liver Assist Device in an ongoing feasibility trial. The results, though preliminary, show potential for keeping patients with chronic liver disease alive long enough to receive a transplant, the company said.

“Patients with chronic liver disease progress toward further and further worsening over time,” Walter Ogier, president/CEO of Arbios, told Medical Device Daily. “They often develop liver sclerosis, or scaring of the liver, and that scaring progresses over time. They tend to be in the hospital every few weeks or months with liver problems.”

While in the hospital, patients with liver disease typically receive hydration therapy — IV fluids — and antibiotics for underling infection, he said.

“There aren’t any really effective ways of treating these patients,” Ogier said.

Arbios’ Sepet Liver Assist Device, a product related to dialysis, cleanses the patients’ blood to help the liver regenerate itself, he said. The strategy is to rid the blood of the “bad actors,” as Ogier calls them, leaving alive and well all the “good actors” in the blood.

The Sepet is a tube-like cartridge — looking much “like a standard kidney dialysis cartridge,” Ogier said — containing several thousand microporous hollow fibers with unique permeability characteristics. When a patients’ blood passes through the fibers, blood plasma components of specific molecular weights pass through the pores, thereby cleansing the blood of harmful impurities, such as hepatic failure toxins as well as various mediators of inflammation and inhibitors of liver regeneration.

These substances would otherwise progressively accumulate in the patient’s bloodstream during liver failure, causing hypotension, increasing risk of sepsis development and accelerating damage to the liver, lungs and other organs, including the brain and kidneys, and suppressing the function and regeneration of the liver, according to Arbios.

Sepet is designed to be used with standard blood dialysis systems available in hospital intensive care units.

“In patients with liver disease it is very difficult for the liver to regenerate. With our Sepet device, we’re trying to remove the bad actors from the blood stream so the liver can regrow and regenerate itself,” Ogier said.

In the study, after one or two days of treatment with Sepet, patients showed improvement in the Glasgow Coma Score and the Fischer Index, common measurements of the severity of encephalopathy, or mental confusion. Ogier also noted trends towards improvement of blood ammonia levels and MELD score, representing common measurements of the severity of liver failure.

Most patients in the study were discharged from the intensive care unit within 48 hours of treatment with improvement of encephalopathy stage.

The data suggest that treatment with Sepet may provide substantial benefit to critically ill patients, Ogier said. “The results have been very encouraging, the product was well-tolerated by the patients, we observed clinical improvement in every patient. [However], these are partial results of a single-arm study.”

During treatment, patients’ blood was perfused using a Prisma dialysis system from Gambro (Stockholm, Sweden) for up to six hours though a Sepet cartridge containing a hollow-fiber membrane permeable to small molecules as well as intermediate molecular weight blood components up to 100 kilodaltons in weight. Vital signs and biochemistries were closely monitored before, during and after each treatment. The clinical trial was recently broadened to accept patients with combined liver failure and renal failure, the company said.

Arbios also is recruiting its 10th patient for the clinical trial. The objective of the study is to assess the safety and tolerability of the Sepet Liver Assist Device as well as its preliminary effectiveness in reversing liver failure and resultant encephalopathy. Patients with acute-on-chronic liver failure, including encephalopathy, are eligible to participate.

In July, Arbios said the University of California at San Francisco (UCSF) Medical Center would serve as an additional clinical site in the trial (MDD, July 14, 2006). Prior to that, in May, the company reported favorable interim safety and patient outcome results of the feasibility clinical trial of the Sepet Liver Assist Device (MDD, May 30, 2006).

The objectives of the trial are to assess the safety and tolerability of Sepet, as well as its preliminary effectiveness in reversing liver failure and resultant encephalopathy.

According to the AASLD, about 4 million Americans are chronically infected with hepatitis C and an estimated 8,000 to 10,000 people die from it each year.

The most reliably curative therapy is liver transplantation, Arbios said, which is costly, limited by the number of available organs and unavailable to a large majority of patients.

According to the American Liver Foundation (New York), about 5,600 liver transplants were performed in 2003, and because of the shortage of organs, more than 1,800 people died that year while waiting for a transplant.

AASLD considers hepatitis C a virus that rarely causes acute illness, but becomes a chronic disease in most infected people. It can lead to cirrhosis and liver cancer. The virus is transmitted through contact with infected blood, contaminated needles, or other sharp instruments, and from infected mother to newborn.

AASLD said hepatitis C is not easily spread through sexual activity, and in about 10% of cases, the route of infection is not known. Most people with hepatitis C do not feel ill or become sick until 20 years after contracting the virus, the AASLD said. Those with long-standing hepatitis may have non-specific symptoms such as fatigue and stomach pains. If hepatitis C progresses to advanced liver disease, patients may develop jaundice, abdominal swelling, internal bleeding or mental confusion. There is no vaccine to prevent hepatitis C.

Ogier said the Sepet trial is ongoing and is enrolling patients “quite rapidly.” He said the company projects completing the trial in two to three months.