Treatment of patients with hepatic failure: the difficult place of liver support systems.
Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure. Demetriou AA, Brown RS Jr, Busuttil RW, Fair J, McGuire BM, Rosenthal P, Am Esch JS 2nd, Lerut J, Nyberg SL, Salizzoni M, Fagan EA, de Hemptinne B, Broelsch CE, Muraca M, Salmeron JM, Rabkin JM, Metselaar HJ, Pratt D, De La Mata M, McChesney LP, Everson GT, Lavin PT, Stevens AC, Pitkin Z, Solomon BA. Liver Support Unit, Department of Surgery, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Suite 8215, North Tower, Los Angeles, CA 90048, USA.


OBJECTIVE
The HepatAssist liver support system is an extracorporeal porcine hepatocyte-based bioartificial liver (BAL). The safety and efficacy of the BAL were evaluated in a prospective, randomized, controlled, multicenter trial in patients with severe acute liver failure.


BACKGROUND
In experimental animals with acute liver failure, we demonstrated beneficial effects of the BAL. Similarly, Phase I trials of the BAL in acute liver failure patients yielded promising results.


METHODS
A total of 171 patients (86 control and 85 BAL) were enrolled. Patients with fulminant/subfulminant hepatic failure and primary nonfunction following liver transplantation were included. Data were analyzed with and without accounting for the following confounding factors: liver transplantation, time to transplant, disease etiology, disease severity, and treatment site.


RESULTS
For the entire patient population, survival at 30 days was 71% for BAL versus 62% for control (P=0.26). After exclusion of primary nonfunction patients, survival was 73% for BAL versus 59% for control (n=147; P=0.12). When survival was analyzed accounting for confounding factors, in the entire patient population, there was no difference between the 2 groups (risk ratio=0.67; P=0.13). However, survival in fulminant/subfulminant hepatic failure patients was significantly higher in the BAL compared with the control group (risk ratio=0.56; P=0.048).


CONCLUSIONS
This is the first prospective, randomized, controlled trial of an extracorporeal liver support system, demonstrating safety and improved survival in patients with fulminant/subfulminant hepatic failure. [Abstract reproduced by permission of Ann Surg 2004;239:660-667; discussion 667-670].
Centre Hepato-Biliaire, Hôpital Paul Brousse, EA 3541, Faculté de Médecine Paris Sud, 94800 Villejuif, France.
Philippe
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Ichai
Didier
D
Samuel