Background & Aims
The neuroprotective effect of the spheroid reservoir bioartificial liver (SRBAL) was
evaluated in a porcine model of drug-overdose acute liver failure (ALF).
Methods
Healthy pigs were randomized into three groups (standard therapy (ST) alone, ST + No-cell device, ST + SRBAL device) before placement of an implantable intracranial pressure (ICP) monitor
and a tunneled central venous catheter. One week later, pigs received bolus infusion
of the hepatotoxin D-galactosamine and were followed for up to 90 h.
Results
At 48 h, all animals had developed encephalopathy and biochemical changes confirming ALF;
extracorporeal treatment was initiated and pigs were observed up to 90 h after drug infusion. Pigs treated with the SRBAL, loaded with porcine hepatocyte
spheroids, had improved survival (83%, n = 6) compared to ST alone (0%, n = 6, p = 0.003) and No-cell device therapy (17%, n = 6, p = 0.02). Ammonia detoxification, peak levels of serum ammonia and peak ICP, and pig
survival were influenced by hepatocyte cell dose, membrane pore size and duration
of SRBAL treatment. Hepatocyte spheroids remained highly functional with no decline
in mean oxygen consumption from initiation to completion of treatment.
Conclusions
The SRBAL improved survival in an allogeneic model of drug-overdose ALF. Survival
correlated with ammonia detoxification and ICP lowering indicating that hepatocyte
spheroids prevented the cerebral manifestations of ALF (brain swelling, herniation,
death). Further investigation of SRBAL therapy in a clinical setting is warranted.
Graphical abstract
Graphical Abstract
Abbreviations:
AD (albumin dialysate), ALF (acute liver failure), BAL (bioartificial liver), ECT (extracorporeal therapy), ICP (intracranial pressure), RALF (recovery acute liver failure), ROS (reactive oxygen species), SRBAL (spheroid reservoir bioartificial liver), ST (standard therapy), NC (No-cell)Keywords
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Article info
Publication history
Published online: March 26, 2015
Accepted:
March 19,
2015
Received in revised form:
March 13,
2015
Received:
October 27,
2014
See Editorial, pages 303–305Identification
Copyright
© 2015 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
