Editor’s note (January 21st 2019): An innovative new machine that keeps livers alive outside of the body received approval from The National Institute for Health and Clinical Excellence on January 16th 2019. The device is expected to greatly increase the availability of livers for transplant—as far more organ donations can be kept healthy until they can be matched with a recipient. The device has been designed to keep livers fully functioning, and provides blood, oxygen, nutrients and temperature control, and is also being tested in America, Europe and India. Similar devices for hearts, lungs and kidneys are bound to follow eventually.This piece, published on January 25th 2018, explains how the device works.
WHEN Constantin Coussios, a biomedical engineer at Oxford University, arrived one day in 2013 at the transplant centre of King’s College Hospital, in London, with a liver for their use, he triggered a brief flurry of panic. Two other livers had arrived at the same time. The hospital had only one operating theatre in which liver transplants could be carried out—and because livers intended for transplant can be kept in cold storage for no longer than 12 hours, the situation looked serious.
What saved the day, and possibly a patient’s life, was that Dr Coussios was bringing not a cold liver, stored on ice, but a warm one. Instead of having had its metabolism slowed, it was fully functional. This was because it was connected to a supply of blood and nutrients inside a special box known as a metra (a Greek word meaning “womb”), invented by Dr Coussios and his colleague Peter Friend. The metra even had a graphical interface to show, moment by moment, how well its cargo was faring. Dr Coussios told the surgeon to transplant the cold-stored livers first. The one he had brought would keep.
That was in the early days of metras. Now, the devices are starting to spread. So far 25 have been deployed around the world and others are about to be. There are also plans, by Dr Coussios and others, to extend the idea behind the metra to the preservation of other vital organs. If that works, it would change the transplant business by improving both the supply and the health of such organs.
A metra is designed to keep the organ it is nurturing supplied with the correct amount of blood—an amount which varies from one instant to the next. It detects the organ’s demand for blood by monitoring pressure in the arteries and veins going into and out of the liver. It then adjusts the power of its pump in response.
The blood in question has been tinkered with to make it more effective. It has had its white cells and platelets removed to avoid inflammation, clotting and the transfer of disease. For the further prevention of clotting, it has had anticoagulants added. And it has been boosted with special chemicals that the liver needs in order to produce bile; with insulin to regulate the organ’s metabolism; and with nutrition in the form of glucose and amino acids.
Once a liver is hooked up inside a metra, its health can be tracked by monitoring things like blood flow, bile production and acidity levels. All these data permit a transplant team to see how the organ is faring. Moreover, a metra not only keeps a liver healthy but can, in some circumstances, actually improve its health. Putting a liver that has been cooled for storage into a metra can reverse damage it has sustained when cold by providing an environment in which its natural propensity to rejuvenate can come to the fore. More remarkably, metras may even be able to recondition livers that are sickly because they contain too much fat, and are thus untransplantable. Once a liver has been removed from the body that was making it fat, it will recover surprisingly quickly. A mere two days in a metra “liver spa” is enough to have a palpable positive effect on the health of such an organ.
At the moment, this last benefit is of only theoretical value, because regulations mean livers for transplant can be stored in a metra for a maximum of 24 hours. That, though, is twice the maximum a liver ought to be kept chilled for transplant, and almost three times the nine-hour limit generally preferred—hence Dr Coussios’s insouciance at the hospital back in 2013. Research on metras suggests that the 24-hour limit could safely be raised to three days, and possibly longer than that.
Twenty-four hours is, though, still long enough to conduct tests on the quality of livers that might otherwise be rejected. The existing assessment of a liver for transplant is necessarily subjective, because there is no sure way to tell if a cooled organ will work normally when it is warmed up and reconnected. Many surgeons therefore err on the side of caution, knowing that if they put a defective liver into a patient, it will probably kill him.
All this means that using metras should increase the availability of livers for transplant. Dr Coussios reckons that reducing the rate of rejection by surgeons could, by itself, double the number which can be used in Britain. Metras could also make it easier to perform the tricky operation of splitting livers in two, which is sometimes done to create a child-sized organ while still leaving enough over to transplant into an adult. The use of a metra is likely to permit these divisions to be carried out more slowly and carefully.
The metra is being commercialised by OrganOx, a firm based in Oxford. Dr Coussios estimates that the world’s hospitals have need for about 300 of the machines, but the firm says it will have reliable repeat business from furnishing the metras it has sold with the disposable plastic connectors that hook machine and organ up together—for a replacement set of these is required with each new liver stored.
In the future, OrganOx hopes to expand its activities by building a metra for kidneys, and perhaps also one for pancreases. Meanwhile, the firm has competition in the form of TransMedics, of Andover, Massachusetts. This company is developing similar devices for livers, hearts and lungs.
Besides increasing the supply of organs, and improving patient outcomes, metras and their competitors can also help ease the psychological burden on surgeons. One such, of some 30 years’ experience, still admits to having sleepless nights after performing a liver transplant. Even if he has done the surgery perfectly, he cannot be sure that the liver he has transplanted will actually work. Metra-storage makes it quite likely that it will.