By Evelyn Harvey
BRUSSELS, Belgium -- March 27, 2009 -- Three or more sessions of albumin dialysis with the Molecular Adsorbent Recirculating System (MARS(R)) extracorporal liver-purification significantly increases transplant-free survival rates in patients with fulminant hepatic failure (FHF), according to results of a treatment, randomised, open-label, active-control, parallel-assignment, efficacy study.
The treatment approach also improved liver and kidney parameters and showed a nonsignificant trend towards lower mortality, according to the research, presented on March 27 at the 29th International Symposium on Intensive Care and Emergency Medicine (ISICEM).
"Despite improvements in liver transplantation, up to 40% of acute liver failure patients die before receiving a transplant or perioperatively. Albumin dialysis with MARS provides a bridge, improving patients' parameters before transplantation or spontaneous regeneration, by removing soluble and albumin-bound toxins from the blood," said study presenter Faouzi Saliba, MD, Paul Brousse Hospital, Villejuif, France.
The MARS Albumin Dialysis System in Patients With Fulminant and Subfulminant Hepatic Failure study is the first prospective randomised, controlled trial of a non-cell artificial liver support.
The researchers enrolled 102 patients with fulminant or subfulminant hepatic failure according to the Clichy and King's College criteria and receiving ICU care. Severely septic patients or those with absolute contraindications for liver transplant were not eligible.
Patients were stratified according to paracetamol (P) aetiology (63 P, 39 nonparacetamol [NP]), and randomised a few hours post arrival to receive either conventional liver support (n = 49) or at least 1 6-hour session of MARS (n = 53).
All baseline characteristics were similar except acidosis, which was significantly higher in the MARS patients (P = .02), and the proportion of P-induced FHF was the same across both groups.
There was no significant difference in transplantation rates between the conventional and MARS groups, but more NP patients were transplanted than P patients (82.5% vs. 41.5%, P < .0001). Almost 90% of patients received transplants within 48 hours of randomisation.
A trend towards MARS benefit was seen in 6-month survival, the primary endpoint, although this difference lacked significance (84.9% MARS vs 75.5% conventional treatment group; P = .28). When analysed according to cohort, P patients with FHF showed a more pronounced trend than NP patients with FHF.
Overall transplant-free survival, the coprimary endpoint, did not differ between groups, although the P group showed a trend towards MARS benefit. However, analysis according to the number of MARS sessions showed a highly significant benefit in patients who received 3 or more treatments (P < .0001). Model for End-Stage Liver Disease score <40 and normal-high fibrinogen were also predictive of transplant-free survival.
MARS treatment significantly reduced bilirubin, urea, creatinine, and lactates compared with the control group. MARS treatment also significantly reduced platelet counts, but this was not associated with significantly increased bleeding adverse events. Rates of adverse events and serious adverse events were similar for the MARS and conventional treatment groups.
"The study demonstrated the safety and efficacy of multiple MARS treatments in critically ill liver failure patients," concluded Professor Saliba. "There were also significant improvements in liver and kidney biological parameters and a higher transplant-free survival rate."
The results suggest further study of MARS would be of benefit, and specific trials in patients awaiting grafts for long periods or who have a contraindication to liver transplantation.
"MARS could also benefit patients where the only graft available is of poor quality, for instance from a high-risk donor," added Professor Saliba.
Funding for trial was provided by Teraklin-France and Laboratoires LFB.
[Presentation title: MARS in Acute Liver Failure: Results of a New Trial.
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