Researchers at the University of Pittsburgh reported on Friday that they had trained the immune systems of a few patients to accept liver transplants without the drugs needed to avoid organ rejection.
Three of eight patients have now been off the drugs for at least three years, perhaps an early step toward a new approach to transplantation that experts in the field have long hoped for. The study was published in Nature Communications.
“They’ve gone a long way toward proving a principle,” said Dr. William Jarnagan, chief of liver and transplant surgery at Memorial Sloan Kettering Cancer Center, who was not involved in the study.
“With further development, it could really be a game changer,” he added.
Dr. Joohyun Kim, a liver transplant surgeon at Yale who was not involved with the study, said, “Even 10 years ago, people thought ‘tolerance induction’ was a dream.”
Although anti-rejection drugs have made organ transplants possible, they come with grave consequences.
The medications, which suppress the body’s immune response, increase the risks of infection, cancer, high cholesterol levels, accelerated heart disease, diabetes and kidney failure. They can even cause hair loss.
Within five years of a liver transplant, 25 percent of patients, on average, have died. Many need kidney transplants because the anti-rejection drugs destroy their kidneys.
“The list of adverse effects is long,” said Dr. Abhinav Humar, chief of abdominal transplant services at the University of Pittsburgh Medical Center. “If you could avoid taking them, you would.”
Efforts to spare patients long-term dependence on anti-rejection drugs date back almost 30 years, said Dr. Angus Thomson, professor of surgery and immunology at the University of Pittsburgh.
The research led to the idea that dendritic cells, a type of immune system cell, could be the key to preventing rejection. These cells help the body distinguish “self” from “non-self,” an external threat.
The idea, which became the basis of the new study, was that perhaps if an organ donor’s dendritic cells were given to a recipient, the patient’s body might learn to accept the new organ.
The research team decided to start with liver transplants rather than the more common kidney transplants. Livers are perhaps the best tolerated transplanted organ.
After taking immunosuppressive drugs for several years, 13 to 15 percent of liver transplant patients are able to stop. Their immune systems do not attack the transplanted livers.
The investigators also elected to test their ideas with living donors. Because the liver can regenerate, doctors sometimes take a piece of a donor’s healthy liver and transplant it. Both the donor and the recipient regrow full-sized livers.
That allowed the researchers to time the surgery so they could give the recipient dendritic cells from the donor before the actual transplant. The hope was that the cells would prime the recipient’s immune system to accept the new liver.
The scientists said it might also be possible to use this method when a donor has died and there is no opportunity to wait before transplanting. Doctors would have to infuse the donor’s dendritic cells a week after the transplant, because it takes a week to isolate and purify them.
The first patient in the Pittsburgh study, Michael Schaffer, got his donor’s dendritic cells and then a new liver in October 2017, but died suddenly and unexpectedly of unrelated causes eight years later. He was taking one anti-rejection drug, at the lowest dose, but was never able to quit it completely.
One of the next patients, Barbara Bowser, did much better.
Ms. Bowser, a 65-year-old retired school cleaner in Punxsutawney, Pa., had no idea her liver was failing. Then one day in December 2016, when she was 56, she felt sick to her stomach, went to the bathroom and passed out.
“The bathroom looked like a crime scene,” Ms. Bowser recalled. “Varices in my esophagus had burst. My liver was not functioning.”
She wanted a living donor transplant, but no relatives were eligible. So, she said, “I put my story on Facebook.” A 33-year-old woman said she would donate.
“We met on the day of the surgery,” on Jan. 25, 2018, Ms. Bowser said. She had received an infusion of the donor’s dendritic cells a week earlier.
Ms. Bowser took anti-rejection drugs for nine months afterward and hated them — they made her feel ill, and her hair fell out. The Pittsburgh doctors were afraid to stop the medications immediately after a transplant.
In October 2019, however, the Pittsburgh surgeons weaned Ms. Bowser off the drugs. She was terrified. “I never thought it would work,” she said.
It has been six and a half years now. Ms. Bowser still has her transplanted liver and is still not taking the drugs. “I feel like my old self,” she said.
Gina Kolata reports on diseases and treatments, how treatments are discovered and tested, and how they affect people.
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