Evaluation of a novel bioartificial liver in rats with complete liver ischemia: treatment efficacy and species-specific alpha-GST detection to monitor hepatocyte viability

Background/Aims: There is an urgent need for an effective bioartificial liv er system to bridge patients with fulminant hepatic failure to liver transp lantation or to regeneration of their own liver. Recently, we proposed a bi oreactor with a novel design for use as a bioartificial liver (BAL). The re actor comprises a spirally wound nonwoven polyester fabric in which hepatoc ytes are cultured (40 . 10(6) cells/ml) as small aggregates and homogeneous ly distributed oxygenation tubing for decentralized oxygen supply and CO2 r emoval. The aims of this study were to evaluate the treatment efficacy of o ur original porcine hepatocyte-based BAL in rats with fulminant hepatic fai lure due to liver ischemia (LIS) and to monitor the viability of the porcin e hepatocytes in the bioreactor during treatment. The latter aim is novel a nd was accomplished by applying a new species-specific enzyme immunoassay ( EIA) for the determination of porcine alpha-glutathione S-transferase (alph a-GST), a marker for hepatocellular damage. Methods: Three experimental groups were studied: the first control group (L IS Control, n=13) received a glucose infusion only; a second control group (LLS No-Cell-BAL, n=8) received BAL treatment without cells; and the treate d group (LIS Cell-BAL, n=8) was connected to our BAL which had been seeded with 4.4 . 10(8) viable primary porcine hepatocytes. Results/Conclusions: In contrast to previous comparable studies, BAL treatm ent significantly improved survival time in recipients with LIS. In additio n, the onset of hepatic encephalopathy was significantly delayed and the me an arterial blood pressure significantly improved. Significantly lower leve ls of ammonia and lactate in the LIS Cell-BAL group indicated that the porc ine hepatocytes in the bioreactor were metabolically activity. Low pig alph a-GST levels suggested that our bioreactor was capable of maintaining hepat ocyte viability during treatment. These results provide a rationale for a c omparable study in LIS-pigs as a next step towards potential clinical appli cation.