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


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.
Shito
Masaya
M
Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Shriners Hospitals for Children, and Harvard Medical School, Boston, Massachusetts 02114, USA.
Tilles
Arno W
AW
Tompkins
Ronald G
RG
Yarmush
Martin L
ML
Toner
Mehmet
M
D000818:Animals; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D017093:Liver Failure / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016031:Liver Transplantation; D019164:Liver, Artificial; D008297:Male; D008858:Microscopy, Phase-Contrast; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D013997:Time Factors