A bioartificial liver that combines plasma dialysis and whole liver perfusion.
OBJECTIVE
The development of a bioartificial liver with xenogeneic hepatocytes requires sufficient hepatocyte mass for metabolic support, decreased immunogenicity, and prevention of viral transmission. Therefore, the authors developed a plasma dialysis system using a selective plasma filter, and combined this dialysis system with whole liver plasma perfusion (PDWLP). In this system, the patient's plasma was dialyzed with normal plasma recycled through the pig liver.


METHODS
Female inbred Large White pigs were used for the hepatic failure model and for liver donation. Fulminant hepatic failure (FHF) was induced by the intraportal administration of alpha-amanitin and lipopolysaccharide. Nine hours after this injection, the FHF pigs were connected to the dialysis system for 6 h (n = 5). Control FHF pigs were not connected to the dialysis system (n = 10).


RESULTS
Animal survival was lengthened, and cardiovascular stability was demonstrated in the PDWLP treated pigs. This system suppressed the production of substances that promote encephalopathy. The liver necrosis and neutrophil infiltration were significantly less in the experimental pigs.


CONCLUSIONS
The experimental treatment attenuated the progression of FHF. Extracorporeal liver, perfused with oxygenated plasma, functioned for 6 h without hyperacute rejection. This type of hybrid bioartificial liver may be useful for treating FHF patients.
Umehara
Minoru
M
Department of Surgery,Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. minoruu@cc.hirosaki-u.ac.jp
Totsuka
Eishi
E
Ishizawa
Yoshiya
Y
Nara
Masaki
M
Hakamada
Kenichi
K
Umehara
Yutaka
Y
Sasaki
Mutsuo
M
D053959:Alpha-Amanitin; D000818:Animals; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation / Q000295:instrumentation; D005260:Female; D008070:Lipopolysaccharides; D017114:Liver Failure, Acute / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D019164:Liver, Artificial; D010101:Oxygen Consumption; D016060:Sorption Detoxification / Q000295:instrumentation*; D013552:Swine
D053959:Alpha-Amanitin; D008070:Lipopolysaccharides