Significant Survival Prolongation in Pigs With Fulminant Hepatic Failure Treated With a Novel Microgravity‐based Bioartificial Liver

Abstract

The aim of this study was to evaluate the efficacy and safety of our novel Innsbruck Bioartificial Liver (IBAL; US patent no. 10/641275), which contains aggregates of porcine hepatocytes grown under simulated microgravity, in a porcine model of fulminant hepatic failure (FHF). FHF was induced by a combination of 75-80% liver resection and ischemia of the remnant segments for 60 min in 12 pigs. Two experimental groups were studied: the control group (n = 5) received standard intensive care and the study group (n = 5) received IBAL treatment. The survival of pigs with FHF was significantly prolonged by about 150% with IBAL treatment as compared to controls (controls: 20.4 +/- 2.8 h, IBAL: 51.0 +/- 2.2 h; P = 0.00184). In addition, intracranial pressure, blood ammonia, lactate, aspartate aminotransferase, and alkaline phosphatase levels were lower in the IBAL group than in controls, indicating metabolic activity of porcine hepatocytes in the bioreactor. No adverse effects were observed.

Development of a Porcine Model of Post-Hepatectomy Liver Failure

“…Arterial Lactate concentrations from baseline and following ALF induction at t ¼ 0 (*P < 0.05 versus sham group, **P < 0.01 versus sham group, ***P < 0.001 versus sham group, ****P < 0.05 versus baseline, *****P < 0.01 versus baseline). [17]. Total protein and albumin levels decreased significantly already from t ¼12 h and t ¼0 h, respectively, partly due to loss of blood (and proteins) during surgery and partly because of the hemodilution caused by infusion of a considerable fluid volume during the 24 h period.…”

“…There is a predicted threshold of liver remnant, below which regeneration does not proceed, and hepatic metabolic function fails. Such fatal models of hepatic failure have been reported after 85% hepatectomy [17,18].…”

“…Accelerated glycolysis in splachnic area may also be implicated[38]. Hochleitner et al[17] demonstrated similar pattern for lactate levels in their model of liver failure. Ammonia (NH 3 ) levels increased significantly by t ¼ 6 h in POLF animals and went on in a similar fashion until the end of the experiment.…”

Future of bioartificial liver support

“…In many different models of ALF several BALs based on animal liver cells have shown to prolong survival significantly in comparison to standard treatment [23][24][25][26][27][28][29][30][31][32][33] .…”

Bioartificial liver devices: Perspectives on the state of the art

“…In another Innsbruck BAL (IBAL), the culture vessel rotated around its longitudinal axis, and the organoid hepatocyte aggregates were formed under simulated microgravity. Reportedly, the survival time of pigs with liver failure was prolonged with this BAL [35,36]. Shinohara developed a new bioreactor based on titanium dioxide, which was able to degrade bilirubin, IL-6, IL-8 and IL-10 using its photocatalysis without impacting albumin expression [37].…”