Improving the utility of split liver transplantation using technical advances and normothermic ex-vivo machine perfusion

Abstract

Split liver transplantation addresses donor shortages by permitting the transplant of two recipients using a single donor liver. Technical advances such as arterial reconstruction and machine perfusion may further improve the utility of these organs, provide the opportunity for novel techniques to be developed, and allow for split liver transplantation to be utilised in ways never previously conceived.

Machine perfusion preserves an organ outside the body and affords the opportunity for real-time testing of organ viability prior to transplant. Extending ex-vivo perfusion into the range of days-to-weeks allows more sophisticated assessment to occur and may also allow time for resuscitation and improvement of these organs. This thesis therefore aimed to explore how split liver transplantation can be improved by expansion of recipient and donor selection criteria and integration with technical advances such as normothermic machine perfusion.

This thesis found that transplantation of adults using split grafts is safe in selected high-risk recipients (high MELD or poor pre-transplant clinical status), and may be improved by technical advances such as the liberal use of arterial interposition grafts. A novel technique of liver splitting using machine perfusion was developed and potentially represents the best of both worlds compared to existing methods. Further, by modifying a commercially available perfusion machine, long-term perfusion of split grafts was achieved. This has the potential to improve the assessment of these grafts, facilitate regeneration and even provide a unique model for translational research. Novel agents are needed to improve the ex-vivo assessment of these organs prior to transplant and indocyanine green was investigated as a liver-specific marker for this purpose. Future work should focus on improving our understanding of an organ’s requirements for long-term ex-vivo survival and validation of our results in the clinical setting.