New concepts in liver preservation: How the pendulum sways back

Alexis Carrel, the French surgeon born in Lyon in 1873, pioneered vascular anastomosis and organ transplantation, for which he was awarded the Nobel Prize in Medicine in 1912. Carrel had a long-time dream of permitting an entire organ to live outside the body for an indefinite time. He realized that to make this true, he needed a pump to perfuse the organ under physiological conditions, forcing oxygen into a continuously circulating fluid. In 1920, he moved to the Rockefeller Institute in New York, where he worked with the great aviator Charles Lindbergh, the first to fly across the Atlantic, as his mechanical alter ego. Together, they devised a perfusion pump that was the forerunner of modern pump oxygenators, as promisingly depicted on the cover of Time in June 1938. Carrel and Lindbergh worked on keeping whole hearts, kidneys, and other organs alive artificially with nutrient perfusion fluids under culture conditions, that is, at normothermia. Hence, with their concept of whole-organ perfusion, their ultimate goal was to immortalize organs by pulsing serum containing nutrients and growth factors through the organ enclosed in an incubator, almost exactly as in life. Now, 70 years later, we have come as far as being able to preserve organs with sustained function ex vivo over 1 night or, in the case of the liver, even less, which is only a minute fraction of the liver’s in vivo lifespan. This issue of Liver Transplantation features an article by Vairetti et al. showing that fatty livers are more susceptible to preservation injury than normal livers and that this type of injury can be reduced by machine perfusion (MP) preservation as opposed to static, cold storage. Liver damage was even further diminished by the use of perfusion preservation at subnormothermic temperatures, with the optimum found in this study to be 20°C. This study addresses 2 issues in liver preservation that have been of elemental interest ever since we first thought of preserving organs ex vivo, that is, preservation using MP and preservation at (sub)normothermic temperatures. The gold standard for preservation of liver grafts to date is washout of the vascular system and static, hypothermic storage using an appropriate organ preservation solution at 4°C. The first solution that permitted extended preservation times for the liver was the University of Wisconsin (UW) solution. The UW solution revolutionized liver transplantation and allowed liver transplants to be performed on a semi-elective basis. Static, hypothermic preservation using a current preservation solution such as UW, histidine tryptophan ketoglutarate, or Celsior provides sufficient protection of livers retrieved from regular, heart-beating donors for up to 14 to 16 hours. The challenge for the future is to use livers of marginal donors such as non–heart-beating donors, elderly donors, or donors with liver steatosis in order to expand the donor pool and relieve some of the pressure on the waiting lists. Several studies have shown that for these marginal livers, preservation by hypothermic, continuous MP is superior to cold storage. This opportunity to increase the number of suitable donor livers has recently revived the interest in hypothermic MP. Liver steatosis in particular, with an estimated prevalence of 30% in cadaveric liver donors, is a reason that many livers are not accepted for transplantation. This prevalence is expected to dramatically increase in the coming years because of the current obesity epidemic. In the setting of (adult) living donor liver transplanta-