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Evaluation of ex-vivo liver perfusion system as a liver support device in a porcine model of liver regeneration
Principal Investigators: Prof. Guy Maddern & Dr. Emma Mullin
Background
The concept of an "artificial liver" has been in development for over 40 years. Such devices aim to temporarily assume metabolic and excretory functions of the liver, with removal of potentially hepatotoxic substances. Patients that may benefit from such devices are those with fulminant hepatic failure, acute-on-chronic liver failure, primary liver allograft non-function and post-hepatectomy liver failure.
The most common reason for hepatic resection in Australia is the excision of colorectal liver metastases. However, one limitation of this type of surgery is the inability to excise all diseased tissue, while at the same time preserving enough hepatic parenchyma to sustain life. Liver support devices may play a future role in extending the current limits on hepatic resection by supporting the remnant through regeneration.
The aim of this project is to monitor the effect of liver support using an ex-vivo liver perfusion system:
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On biochemical and clinical parameters reflecting liver function.
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On liver regeneration and factors known to promote this.
Project Progress
To date we have successfully established the techniques of harvesting a porcine liver and establishing perfusion on an extracorporeal circuit. We have achieved success in maintaining adequate oxygenation via use of a hollow fibre oxygenator. Initial work highlighted the need to overcome peripheral blood shunting and ischaemia of the liver periphery most likely secondary to microvascular spasm and microemboli. Following trials using different agents we are now using an infusion of Glyceryl Trinitrate (GTN), which has improved peripheral perfusion and improved the health of the liver. Individual perfusion of the hepatic artery and portal vein has been successful with appropriate perfusion pressures maintained by use of GTN. We have achieved stability of liver function tests and have demonstrated bile production by the perfused liver. Glucose homeostasis is also satisfactory, with infusion of a combination of insulin, glucose and amino acids in order to provide the liver with nutritional and energy substrate.
To date we have achieved success in perfusing a liver for up to 20 hours.
Future Work
Further work still need to be undertaken to perfect the extracorporeal liver perfusion, mainly in reduction of haemolysis and accurate assessment of blood flows. Once we have reproducibly attained viability we will begin the process of applying this technique to pigs that have undergone a 70% hepatectomy to assess the regenerative response both in terms of physical, biochemical and cytokine parameters.
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