Thousands die waiting for liver transplants. This tactic could yield more organs.
More than 1,000 donated livers are discarded each year because they are too old, fatty, or damaged for transplant. This Drexel physician wants to rescue some of them.
The object in David J. Reich's gloved hands looked like a deflated football: oblong in shape, dull brown in color.
It was a human liver, removed more than a day earlier from the body of an organ donor, and under ordinary circumstances it would have been thrown out. The liver had gone too long without oxygen, deteriorating to the point that it was deemed unsafe to transplant into another person.
Reich, head of transplant programs at Hahnemann University Hospital, was determined to give it new life.
He placed the liver in a basin, connected it to some tubing, and switched on a sophisticated pump — delivering a rich mixture of oxygenated blood, anti-inflammatory compounds, and nutrients to the organ. Within minutes, it started to turn pink.
Each year in the United States, more than 2,500 people die while waiting to receive liver transplants or become too sick to undergo the surgery and must be removed from the wait list. As with hearts, kidneys, and lungs, there simply are not enough livers to go around. To increase the supply, researchers are pursuing a variety of strategies to rejuvenate "marginal" organs — those discarded because they are decayed, diseased in some way, or simply too old.
Reich, also a professor at Drexel University College of Medicine, has high hopes for the pump-like contraption that was turning the brownish liver pink. The technique is called machine perfusion, and it flips a long-accepted practice on its head.
Rather than keep livers on ice to prevent decay until the moment they are transplanted, physicians use such devices to maintain organs at body temperature, with blood and other fluids circulating as they do in a living person.
Lungs, kidneys, and hearts preserved in this manner have been successfully transplanted, and early trials with perfused livers also have shown promise — though the method is more costly than cold storage, and it remains in the research phase in the United States.
Reich is testing such a device in a lab at Gift of Life, the Philadelphia-based nonprofit that recovers donated organs from more than 130 hospitals in eastern Pennsylvania, South Jersey, and Delaware.
He is trying an added wrinkle, collaborating with researchers at England's University of Birmingham and at Massachusetts General Hospital. In addition to blood and nutrients, a third ingredient is used: an experimental golden fluid.
Reich calls it "the juice."
The liver is a marvel of biology, accomplishing an assortment of tasks that, at a glance, seem unrelated. It makes essential proteins for blood clotting. It breaks down fat to produce energy. It stores iron and other essential minerals, delivering them to the bloodstream as needed. It neutralizes toxic substances and helps regulate cholesterol. And when it fails, often the only option is a new one.
The first successful human liver transplant took place more than 50 years ago, but only since 1980 has the practice become widespread, as surgeons honed techniques and learned which donated organs worked best.
A liver from a brain-dead donor — one who has suffered an irreversible loss of brain function — is ideal. With the help of a ventilator, the organ functions in the donor's body up until the moment it is removed for transplant, maximizing the chance of success.
Less ideal is a liver from a donor who dies of cardiac death — generally, a gravely ill person for whom family members have chosen to remove life support. The liver is starved of oxygen for a time as the heart slows and finally stops. If that period is too long, the bile ducts can become blocked, and mitochondria — the "power plants" in each liver cell — lose steam. That liver will not work as well when implanted in another person's body.
Other difficulties arise if a donor liver is too fatty — increasingly an issue with the obesity epidemic — or simply too old.
Reich is optimistic that he can make headway against all these problems.
The brownish liver he was testing at Gift of Life, in Philadelphia's Old City neighborhood, came from an older donor and had gone without oxygen for too long. Reich was assisted by Carol Lam, a research nurse at Drexel, and Stewart Rodes, a nurse from a San Diego-based startup called Vital Therapies.
The team tracked the liver's progress for several hours as it changed from brown to pink to a rich burgundy. The color was encouraging, but the real test would come from analyzing the perfusion fluid on its way into the organ and after it came out.
Would the liver clear itself of toxins? Would it start to make bile, an essential substance in the body's filtration process? Would there be elevated levels of lactate — a sign that the organ's cells had been deprived of oxygen?
"What's the flow?" Reich called out from behind his surgical mask.
"Sixty milliliters. Fifty-seven milliliters," he was told.
The physician gingerly touched the liver in its cradle in the Liver Assist device, made by Organ Assist in the Netherlands. He began to get excited.
"This is a beautiful pink," he said. "It has a nice, soft, healthy texture."
Mixed in with the blood and nutrients was the experimental "juice" — a mixture of anti-inflammatory chemicals and growth factors that had been derived from liver cells kept alive in a California laboratory.
The fluid was made by Vital Therapies, whose core business is a related technology for rescuing diseased livers in live patients. In September, the startup announced that early results from testing that process were inconclusive.
But Reich, who came up with the idea of using the fluid to revive donor livers, still thinks it can help in that regard. He cited the results of a preliminary study with his University of Birmingham collaborators, showing that donor livers perfused with both blood and the added fluid seemed to regain normal function.
"These livers suck up oxygen like there's no tomorrow," Reich said. "They're like a guy in a desert who hasn't seen water for a few days."
The next step is to split donor livers in two, perfusing half of each one with just blood and nutrients and half with the addition of the juice. Reich's counterpart at Birmingham, Richard Laing, is in the early stages of such tests.
Regardless of the effectiveness of the added juice, Reich and other physicians have high hopes for the general concept of circulating body-temperature fluid through the organs before transplant.
Compared with keeping organs on ice, a primary advantage of warm perfusion is reduced inflammation, said David P. Foley, a transplant surgeon with University of Wisconsin Health.
When a liver is removed from ice for transplant, there can be inflammation as the cells resume normal function. When livers are preserved at body temperature, on the other hand, any inflammation can be brought under control before transplant.
"You can kind of go through this inflammation while the liver is sitting in the machine and it's not inside the patient," said Foley, a board member of the American Society of Transplantation.
What's more, keeping a liver "animated" at body temperature allows physicians to test its function, making sure it is as healthy as possible before implanting it into the recipient, said Robert Ashley, chief technical officer at Vital Therapies.
Gift of Life is an active supporter of such research, said Rick Hasz, vice president of clinical services. Of the 2,000 organs recovered by the nonprofit last year, 500 were deemed not suitable for transplant but nevertheless played a valuable role in studies such as Reich's.
Whether donor organs are transplanted or used for study that could save more lives down the road, "families want to be able to help somebody else," Hasz said.
After several hours, the liver Reich was testing showed strong signs of health. It was using oxygen. Lactate levels were dropping. And from a vessel called the hepatic duct, a honey-like substance began to emerge: bile.
"This is fantastic," the Drexel professor said. "See how golden that is?"
To Reich, the liver looked so healthy that he wished he could transplant it right away. More study is needed before that can happen. But if he and his colleagues prove they can bring these rejected livers back to life, it will mean new life for patients as well.