Extracorporeal Liver Perfusion as Liver Support Device: A Pilot Study
thesisposted on 2012-09-28, 15:13 authored by Jai Bikhchandani
Introduction: A liver support device can bridge a patient in acute liver failure safely to transplant. An extracorporeal perfused porcine liver (ECLP) circumvents the limitations of hepatocyte based bioartificial liver, but its clinical application has been limited so far due to the potential risk of transmission of porcine endogenous retroviruses. Aim of this study was to develop an ECLP model that can provide artificial hepatic support across a semi-permeable membrane which should block porcine viruses due to its pore size. Methods: 50-60 Kg white landrace pigs treated with standard abattoir animal procedures were used as donors. The liver was perfused with normothermic autologous oxygenated blood using Medtronic BioMedicus BP560 driven centrifugal pump for 6 hours. This ECLP system was used to support a surrogate patient circulation across the filter Evaclio EC4A. Substances like galactose, ammonia, midazolam and para-aminobenzoic acid, were infused into the surrogate patient and their clearance was calculated. The study was designed as test (n=15) vs. control (n=5); with control experiments having no liver in the circuit. Results: After the optimization phase (n=23), we successfully perfused 15 porcine livers with the mean hepatic artery pressure of 87 mm Hg and flows of 1.2 L /min. Retention of Indocyanine green at 15 minutes was 11% in test and 96% in controls. Mean ammonia clearance of 945 mg/min/kg, galactose Vmax of 111.7 mg/min/Kg, hippurate ratio of 91% and a variable midazolam clearance was seen in the test experiments. Conclusion: The study was successful in proving the feasibility of an ECLP model based on abattoir animals that can be utilised for future research work. This model was able to provide adequate support to the surrogate patient across a hollow filter. Further work is needed to show that an ECLP system can be used in an anhepatic animal prior to application in human trials.
Date of award2012-06-22
Awarding institutionUniversity of Leicester