Pivotal preclinical trial of the spheroid reservoir bioartificial liver

摘要: Background & Aims The neuroprotective effect of the spheroid reservoir bioartificial liver (SRBAL) was evaluated in a porcine model drug-overdose acute failure (ALF). Methods Healthy pigs were randomized into three groups (standard therapy (ST) alone, ST+No-cell device, ST+SRBAL device) before placement an implantable intracranial pressure (ICP) monitor and tunneled central venous catheter. One week later, received bolus infusion hepatotoxin D-galactosamine followed for up to 90h. Results At 48h, all animals had developed encephalopathy biochemical changes confirming ALF; extracorporeal treatment initiated observed 90h after drug infusion. Pigs treated with SRBAL, loaded hepatocyte spheroids, improved survival (83%, n=6) compared ST alone (0%, n=6, p =0.003) No-cell device (17%, =0.02). Ammonia detoxification, peak levels serum ammonia ICP, pig influenced by cell dose, membrane pore size duration SRBAL treatment. Hepatocyte spheroids remained highly functional no decline mean oxygen consumption from initiation completion Conclusions allogeneic ALF. Survival correlated detoxification ICP lowering indicating that prevented cerebral manifestations ALF (brain swelling, herniation, death). Further investigation clinical setting is warranted.