Abstract
Bioartificial livers (BAL) may offer acute liver failure (ALF) patients an opportunity for cure without liver transplantation. We evaluated the efficacy of a spheroid-based BAL system, containing aggregates of porcine hepatocytes, in a porcine model of ALF. ALF pigs were divided into three groups. The control group consisted of treatment naïve pigs (n = 5), blank group consisted of pigs that were attached to the BAL system not containing hepatocytes for 12 hours (n = 5) and BAL group consisted of pigs that were attached to the BAL containing hepatocytes for 12 hours (n = 5). Increase in serum ammonia levels were significantly greater in the blank group (P < 0.01) and control group (P < 0.01), compared to the BAL group during the treatment period. Increase in ICP was significantly greater in the control group compared to the BAL group (P = 0.01). Survival was significantly prolonged in the BAL group compared to the blank group (P = 0.03). A BAL system with a bioreactor containing hepatocyte spheroids showed effective clearance of serum ammonia, preservation of renal function and delayed ICP increase in a porcine model of ALF.
Highlights
Bioartificial liver (BAL) support offers a potential means of improving survival of ALF patients by providing partial liver function until a suitable donor liver is found or the native liver undergoes regeneration
Functional performance of the BAL system as shown by the specific oxygen uptake rate of hepatocyte spheroids remained unchanged throughout the 12-hour procedure (Fig. 1)
The principal finding of this study is that during 12 hours of treatment with a BAL system using immobilized hepatocyte spheroids in surgically-induced porcine model of ALF, survival was significantly prolonged compared to pigs receiving liver support treatment without hepatocytes
Summary
Bioartificial liver (BAL) support offers a potential means of improving survival of ALF patients by providing partial liver function until a suitable donor liver is found or the native liver undergoes regeneration. Previous studies have suggested that ALF patients treated using BAL maintain a more stable medical condition, which may positively influence outcome after LT3. Majority of BAL systems consist of a hollow fiber cartridge packed with single hepatocytes. In previous in vitro studies, hepatocyte spheroids were found to have greater liver-specific functions than dispersed single hepatocytes, especially, in terms of detoxification of plasma and serum[4,5,6].
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