Efficacy of an extracorporeal flat-plate bioartificial liver in treating fulminant hepatic failure

Masaya Shito, Arno W. Tilles, Ronald G. Tompkins, Martin Yarmush, Mehmet Toner

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background. Fulminant hepatic failure is associated with a high mortality rate. Orthotopic liver transplantation is the only established treatment for patients who do not respond to medical management. A major limitation of this treatment is a shortage of donor organs, resulting in many patients dying while waiting for a transplant. An extracorporeal bioartificial liver (BAL) has the potential to provide temporary support for patients with fulminant hepatic failure (FHF) and for patients awaiting orthotopic liver transplantation. We developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. Materials and methods. Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering 2 intraperitoneal injections of D-galactosamine (GalN) (1.2 g/kg) at a 12-h interval. The rats were connected to a BAL device 24 h after the first GalN injection and underwent extracorporeal perfusion for a duration of 10 h. Liver histology, liver-specific markers, and animal survival up to 168 h (7 days) were examined. Results. Histologically, liver damage was reduced in the animal group treated with the hepatocyte-based BAL device. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). Conclusions. This flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GalN-induced FHF.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalJournal of Surgical Research
Volume111
Issue number1
DOIs
StatePublished - May 1 2003
Externally publishedYes

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Artificial Liver
Acute Liver Failure
Equipment and Supplies
Membrane Oxygenators
Hepatocytes
Liver Transplantation
Liver
Swine
Galactosamine
Prothrombin Time
Jugular Veins
Intraperitoneal Injections
Carotid Arteries
Ammonia
Catheterization
Histology
Therapeutics
Perfusion
Tissue Donors
Transplants

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Shito, Masaya ; Tilles, Arno W. ; Tompkins, Ronald G. ; Yarmush, Martin ; Toner, Mehmet. / Efficacy of an extracorporeal flat-plate bioartificial liver in treating fulminant hepatic failure. In: Journal of Surgical Research. 2003 ; Vol. 111, No. 1. pp. 53-62.
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Efficacy of an extracorporeal flat-plate bioartificial liver in treating fulminant hepatic failure. / Shito, Masaya; Tilles, Arno W.; Tompkins, Ronald G.; Yarmush, Martin; Toner, Mehmet.

In: Journal of Surgical Research, Vol. 111, No. 1, 01.05.2003, p. 53-62.

Research output: Contribution to journalArticle

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N2 - Background. Fulminant hepatic failure is associated with a high mortality rate. Orthotopic liver transplantation is the only established treatment for patients who do not respond to medical management. A major limitation of this treatment is a shortage of donor organs, resulting in many patients dying while waiting for a transplant. An extracorporeal bioartificial liver (BAL) has the potential to provide temporary support for patients with fulminant hepatic failure (FHF) and for patients awaiting orthotopic liver transplantation. We developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. Materials and methods. Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering 2 intraperitoneal injections of D-galactosamine (GalN) (1.2 g/kg) at a 12-h interval. The rats were connected to a BAL device 24 h after the first GalN injection and underwent extracorporeal perfusion for a duration of 10 h. Liver histology, liver-specific markers, and animal survival up to 168 h (7 days) were examined. Results. Histologically, liver damage was reduced in the animal group treated with the hepatocyte-based BAL device. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). Conclusions. This flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GalN-induced FHF.

AB - Background. Fulminant hepatic failure is associated with a high mortality rate. Orthotopic liver transplantation is the only established treatment for patients who do not respond to medical management. A major limitation of this treatment is a shortage of donor organs, resulting in many patients dying while waiting for a transplant. An extracorporeal bioartificial liver (BAL) has the potential to provide temporary support for patients with fulminant hepatic failure (FHF) and for patients awaiting orthotopic liver transplantation. We developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. Materials and methods. Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering 2 intraperitoneal injections of D-galactosamine (GalN) (1.2 g/kg) at a 12-h interval. The rats were connected to a BAL device 24 h after the first GalN injection and underwent extracorporeal perfusion for a duration of 10 h. Liver histology, liver-specific markers, and animal survival up to 168 h (7 days) were examined. Results. Histologically, liver damage was reduced in the animal group treated with the hepatocyte-based BAL device. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). Conclusions. This flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GalN-induced FHF.

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