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New Studies Help Establish Potential of Artificial Liver Support Devices

Commenting on the studies, Professor Burroughs from the Royal Free Hospital NHS Trust, London UK, said: "The accepted prognosis for these patients is generally poor and current treatment strategies involve supportive therapy, with the hope that liver function will recover if sufficient time is allowed. Extracorporeal support systems such as the two included in these studies are very useful bridges, but the overall data on survival is disappointing. The positive data for severely ill patients with hepatorenal syndrome I or a MELD score over 30, though, does offer some encouragement."

About the studies

In the first study, 145 patients with cirrhosis and rapid deterioration of their liver function were recruited across seven European countries. This study is the first large prospective randomized controlled trial on the survival of patients with the condition (HELIOS study). Prometheus is a new extracorporeal liver support system allowing the removal of protein bound and water soluble toxins by fractionated plasma separation and absorption (FPSA). Patients were randomized to standard medical therapy or standard medical therapy plus FPSA and the primary endpoints of the study were survival at 28 and 90 days regardless of liver transplantation.

The results show that difference in the overall survival was not statistically different overall (66% vs. 63% p=0.7 at day 28 and 47% vs. 38% p=0.35 at day 90). Only in pre-defined patient sub-groups with hepatorenal syndrome type I* and MELD** score > 30 was a significant survival benefit with treatment with FPSA observed (p=0.04 and p=0.02 respectively).

(*Hepatorenal syndrome type I is a common type of rapidly progressive kidney failure that affects individuals with liver cirrhosis, with a doubling of serum creatinine to a level greater than 2.5 mg/dL or a halving of the creatinine clearance to less than 20 mL/min over a period of less than two weeks.)

(**The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the severity of chronic liver disease. MELD uses the patient's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival.)

In the second study, 189 patients with acute-on-chronic liver failure across six European countries were randomized either to treatment with the Molecular Adsorbent Recirculating System (MARS) or to standard therapy. Treatment with MARS was scheduled at low dose (up to ten sessions of 6-8 hours during 21 days) and the main endpoint was survival at 28 days.

Results showed a significant decrease in serum creatinine (20.0 +/- 33.1% vs. 6.4 +/-33.5% p=0.02) and bilirubin (26.4 +/- 26.1% vs. 8.9 +/- 22.3% p=0.001) as well as higher improvement in the hepatic encephalopathy (estimated by the percentage of evaluations in which HE decreased from II-IV at inclusion to 0-I during therapy, 56% vs. 39% p=0.06) in the MARS group. The primary endpoint was not met however, with the proportion of patients dying within 28 days almost identical in both groups (40.8% vs 40.0%). Findings show that MARS at low dosage is a safe procedure which has significant dialysis effect and improves severe hepatic encephalopathy in patients with cirrhosis and rapid deterioration of their liver function; however a significant beneficial effect on survival could not be demonstrated.

About EASL

EASL is the leading European scientific society involved in promoting research and education in hepatology. EASL attracts the foremost hepatology experts as members and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European Liver policy.

Meeting of the European Association for the Study of Liver (EASL) adds to the growing body of evidence supporting the clinical benefits of Gambro's Molecular Adsorbents Recirculating System (MARS) therapy.

The RELIEF trial -- the largest trial to date involving the use of extracorporeal liver support -- compared MARS therapy to standard medical therapy in patients with acute-on-chronic liver failure (AOCLF.) Treatment of AOCLF is one of the relatively new MARS applications and the purpose of the RELIEF trial was to assess its efficacy and safety for this indication.

The RELIEF trial demonstrated a significant decrease in serum bilirubin and creatinine levels and an improvement in hepatic encephalopathy for patients treated with MARS therapy in comparison to patients receiving standard medical therapy. Although the study did not demonstrate a statistically significant difference in survival between MARS therapy and standard medical therapy, as indicated in the trial abstract and in the press release issued by EASL, the RELIEF findings show that MARS therapy, at low dosage, is a safe procedure, which has significant dialysis effect and improves severe hepatic encephalopathy in patients with cirrhosis and rapid deterioration of their liver function.

The MARS therapy is today the most widely used extracorporeal liver support therapy. This therapy has been in clinical use since 1993 and commercially available since 1999. Its clinical indications are many, including AOCLF, acute liver failure, graft dysfunction after liver transplantation, liver failure after hepatic resection, intractable pruritus in cholestatic liver diseases, and drug overdose and poisoning. The MARS system is used in 45 countries around the world and its safety and efficacy have been demonstrated by clinical experience with more than 9,000 patients (about 36,000 treatments) who have benefited from its use.

"This latest clinical trial adds additional evidence to support that MARS is an important therapeutic tool in controlling the most serious complications of liver disease," says Dr. Josep Torner, Medical Director of Gambro's Liver Business. "An ongoing collaboration with the hepatology community is critical to better define the indications for MARS and improve our understanding of the mechanisms of liver failure."

(In the U.S., the MARS system is cleared for use in the treatment of drug overdose and poisonings only. It is not indicated in the U.S. for the treatment of chronic liver conditions or as a bridge to liver transplant.)

Investigator affiliations:

MARS: Liver Unit, Hospital General Universitario Gregorio Maranon, CIBEREHD, Madrid, Spain; Department and Lab of Hepatology, University Hospitals, Leuven, Belgium; Dept. Hepatolog, Rigshospitalet, Copenhagen, Denmark; Institute of Hepatology, University College London, London, UK; Servicio de Gastroenterologia, Hospital Ramon y Cajal; University of Alcala, CIBEREHD, Madrid, Spain; First Department of Medicine, Martin-Luther-University, Halle, Germany.

Prometheus: Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Hannover, Germany; Department of Nephrology & Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany; Department of Internal Medicine III & Department of Internal Medicine I, Goethe University, Frankfurt/Main, Germany; Ghent University Hospital, Gent, Belgium; Liver Unit, Hospital Clinic, Barcelona, Spain; Department of Nephrology & Hypertension, Medical School Hannover, Hannover, Germany; Medical Department, University of Mainz, Mainz, Germany; Semeiotica Medica, University of Bologna, Bologna, Italy; Institute of Liver Studies, King's College Hospital, London, UK; Paracelsus Medical University Salzburg, Salzburg, Austria; University Hospital Merkur, Zagreb, Croatia; Fresenius Medical Care, Bad Homburg, Germany.