Characteristics of human non-cirrhotic and cirrhotic liver sections in a novel ex vivo perfusion system

Introduction: Animal models or isolated liver cells serve to initially investigate safety of novel drugs and to examine liver diseases. Data gathered from these models may not always be directly transferred into the human system and are subject to certain limitations. Thus we present a perfusion system of human liver tissue, as a new model for translational research. Methods: Human liver tissue specimens from non-cirrhotic (NC, n=9) and cirrhotic (CL, n=8) origin were perfused continuously for six hours. Hourly taken samples from perfusate were analyzed for markers of general metabolism, hepatic synthesis capacity, liver cell damage and for hepatic functionality. Results: Glucose release was observed for NC tissue during the entire perfusion period, while in CL tissue the mean values turned to consumption after four hours. Lactate production and release of bile acids were significantly increased in the CL tissue. Albumin production and release of the liver enzymes LDH, ALT, GLDH and γGT were significantly higher in NC tissue. Cell death markers M60 and M35 increased in both tissue types during perfusion, but not differ significantly between the groups. The conversion of the three cytochrome P450 substrates phenacetin, midazolam and diclofenac indicated faster phase I and phase II transformations in NC tissue. H&E-stain demonstrated native hepatic architecture, which remained largely unaffected by perfusion. Conclusion: Ex vivo perfusion of human liver tissue allows analysis of functional and metabolic parameters and liver specific factors, reflecting the in-vivo situation observed in patients. As the tissue structure is preserved in this system, also interaction of parenchymal and non-parenchymal cells could be studied. Improvement in oxygen and nutrient supply may further prolong the duration cells can be kept in a functional state.