Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure

Achilles A. Demetriou, Robert S. Brown, Ronald W. Busuttil, Jeffrey Fair, Brendan M. McGuire, Philip Rosenthal, Jan Schulte Am Esch, Jan Lerut, Scott L. Nyberg, Mauro Salizzoni, Elizabeth A. Fagan, Bernard De Hemptinne, Christoph E. Broelsch, Maurizio Muraca, Joan Manuel Salmron, John M. Rabkin, Herold J. Metselaar, Daniel Pratt, Manuel De La Mata, Lawrence P. McChesneyGregory T. Everson, Philip T. Lavin, Anthony C. Stevens, Zorina Pitkin, Barry A. Solomon, J. Michael Henderson, Ravi S. Chari, William C. Meyers, William C. Wood

Research output: Contribution to journalArticle

464 Citations (Scopus)

Abstract

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. Summary Background Data: 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.

Original languageEnglish (US)
Pages (from-to)660-670
Number of pages11
JournalAnnals of Surgery
Volume239
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

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Artificial Liver
Acute Liver Failure
Multicenter Studies
Randomized Controlled Trials
Survival
Liver Transplantation
Odds Ratio
Safety
Liver
Population
Hepatocytes
Swine
Transplants

ASJC Scopus subject areas

  • Surgery

Cite this

Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure. / Demetriou, Achilles A.; Brown, Robert S.; Busuttil, Ronald W.; Fair, Jeffrey; McGuire, Brendan M.; Rosenthal, Philip; Am Esch, Jan Schulte; Lerut, Jan; Nyberg, Scott L.; Salizzoni, Mauro; Fagan, Elizabeth A.; De Hemptinne, Bernard; Broelsch, Christoph E.; Muraca, Maurizio; Salmron, Joan Manuel; Rabkin, John M.; Metselaar, Herold J.; Pratt, Daniel; De La Mata, Manuel; McChesney, Lawrence P.; Everson, Gregory T.; Lavin, Philip T.; Stevens, Anthony C.; Pitkin, Zorina; Solomon, Barry A.; Henderson, J. Michael; Chari, Ravi S.; Meyers, William C.; Wood, William C.

In: Annals of Surgery, Vol. 239, No. 5, 05.2004, p. 660-670.

Research output: Contribution to journalArticle

Demetriou, AA, Brown, RS, Busuttil, RW, Fair, J, McGuire, BM, Rosenthal, P, Am Esch, JS, Lerut, J, Nyberg, SL, Salizzoni, M, Fagan, EA, De Hemptinne, B, Broelsch, CE, Muraca, M, Salmron, JM, Rabkin, JM, Metselaar, HJ, Pratt, D, De La Mata, M, McChesney, LP, Everson, GT, Lavin, PT, Stevens, AC, Pitkin, Z, Solomon, BA, Henderson, JM, Chari, RS, Meyers, WC & Wood, WC 2004, 'Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure', Annals of Surgery, vol. 239, no. 5, pp. 660-670. https://doi.org/10.1097/01.sla.0000124298.74199.e5
Demetriou, Achilles A. ; Brown, Robert S. ; Busuttil, Ronald W. ; Fair, Jeffrey ; McGuire, Brendan M. ; Rosenthal, Philip ; Am Esch, Jan Schulte ; Lerut, Jan ; Nyberg, Scott L. ; Salizzoni, Mauro ; Fagan, Elizabeth A. ; De Hemptinne, Bernard ; Broelsch, Christoph E. ; Muraca, Maurizio ; Salmron, Joan Manuel ; Rabkin, John M. ; Metselaar, Herold J. ; Pratt, Daniel ; De La Mata, Manuel ; McChesney, Lawrence P. ; Everson, Gregory T. ; Lavin, Philip T. ; Stevens, Anthony C. ; Pitkin, Zorina ; Solomon, Barry A. ; Henderson, J. Michael ; Chari, Ravi S. ; Meyers, William C. ; Wood, William C. / Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure. In: Annals of Surgery. 2004 ; Vol. 239, No. 5. pp. 660-670.
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abstract = "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. Summary Background Data: 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.",
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TY - JOUR

T1 - Prospective, Randomized, Multicenter, Controlled Trial of a Bioartificial Liver in Treating Acute Liver Failure

AU - Demetriou, Achilles A.

AU - Brown, Robert S.

AU - Busuttil, Ronald W.

AU - Fair, Jeffrey

AU - McGuire, Brendan M.

AU - Rosenthal, Philip

AU - Am Esch, Jan Schulte

AU - Lerut, Jan

AU - Nyberg, Scott L.

AU - Salizzoni, Mauro

AU - Fagan, Elizabeth A.

AU - De Hemptinne, Bernard

AU - Broelsch, Christoph E.

AU - Muraca, Maurizio

AU - Salmron, Joan Manuel

AU - Rabkin, John M.

AU - Metselaar, Herold J.

AU - Pratt, Daniel

AU - De La Mata, Manuel

AU - McChesney, Lawrence P.

AU - Everson, Gregory T.

AU - Lavin, Philip T.

AU - Stevens, Anthony C.

AU - Pitkin, Zorina

AU - Solomon, Barry A.

AU - Henderson, J. Michael

AU - Chari, Ravi S.

AU - Meyers, William C.

AU - Wood, William C.

PY - 2004/5

Y1 - 2004/5

N2 - 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. Summary Background Data: 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.

AB - 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. Summary Background Data: 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.

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