Transplant surgeons at two US hospitals are about to do something long considered taboo: put kidneys from donors with hepatitis C into recipients without the infection.
In first-in-the-world clinical trials scheduled to launch later this spring, independent teams from the University of Pennsylvania and Johns Hopkins University will take kidneys from deceased carriers of the hep C virus, put them into patients with renal failure, and then give them a 12-week course of an antiviral therapy in the hopes that they will emerge infection-free.
If successful, the trials could enable hundreds of transplants each year for patients who might otherwise die waiting for a kidney.
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“This trial is like a crystalizing moment,” said Dr. Peter Reese, a transplant nephrologist from Penn, describing the plans publicly for the first time. “Telling someone that you want to give them hepatitis C now seems like a reasonable thing to do if it can facilitate a transplant.”
Currently, more than 100,000 Americans are on the wait list for a kidney, with an average wait time of three to five years. An estimated 5 percent of patients die each year before they receive a kidney, and the mortality rates increase for diabetics and the elderly.
The idea behind the two upcoming trials is to take older patients who have long waits ahead and don’t have living donors, and allow them to jump the queue — if they’re willing to take on a bit more risk.
The risk of hep C infection is deemed manageable, and ethically acceptable, thanks to the latest wave of hep C medications, which offer cure rates of 95 percent and higher.
“For a 60-year-old diabetic who doesn’t have a living donor, who hasn’t been on the wait list very long, they’re miserable on dialysis, their mortality rate is high — that person might roll the dice on this and say, ‘You know what? These drugs work, and it’s worth it to me to get off dialysis sooner,’” said Dr. Heather Morris, a nephrologist at the Columbia University Medical Center.
“Initially, we’re targeting the population that has the highest mortality risk while waiting for a transplant,” explained Dr. Christine Durand, a transplant infectious disease specialist at Johns Hopkins. But if the technique proves safe and effective, she added, organs from hep C patients might one day join the regular organ pool.
“If it was me who needed a kidney,” Durand said, “I would sign up for this.”
Not all transplant experts are as gung-ho about using infected kidneys in this way.
Mark Schnitzler, a health economist and director of transplant outcomes and policy research at Saint Louis University, described himself as “quite skeptical.”
“Either the treatment success expectations would need to be excellent with minimal complications, or there would need to be unusual circumstances that limit access to alternative deceased donor kidneys,” he said.
Both the Penn and Hopkins studies are backed by Merck, the drug company that makes Zepatier, the latest hep C agent to hit the market. The company is supplying its $54,500-per-patient medicine for free and providing additional financial support for staff and lab tests.
With the funding secured, both the Penn and Hopkins teams said they plan to file for regulatory approval in the coming weeks — and trials at other transplant centers could be up and running soon.
Earlier this month, Morris and her colleagues applied to a major drug company for support to run a comparable trial in New York; and Dr. Jayme Locke, a transplant surgeon at the University of Alabama at Birmingham, is in discussions with her hospital review board to do the same.
“This is an exciting idea because there’s such an organ shortage, and we certainly don’t optimize the use of hepatitis C-positive kidneys,” Locke said.
The plan is for transplant recipients to start taking antiviral medications right around the times of surgery to clear the virus from the infected kidney and anywhere it might have spread in the rest of the body.
The drugs aren’t foolproof, though, and invariably some small fraction of transplant patients will develop hepatitis because of this procedure.
But just because someone catches hepatitis doesn’t mean they will necessarily develop cirrhosis and other complications associated with the disease. Some may live out their days carrying the virus but suffering few ill effects.
“My guess,” said Locke, “is that it’ll be something else that takes their lives that’s more common in kidney patients,” like a heart attack.
For the past 20 years, transplant centers have only offered hep C-infected kidneys to hep C-infected recipients, which has led to a lot of waste. According to calculations published last year by Reese and his colleagues, only 37 percent of the usable kidneys from deceased donors with hep C were transplanted nationwide between 2005 and 2014. The rest, amounting to an estimated 400 infected kidneys per year, were thrown away.
And that estimate could be low. For one thing, it doesn’t include all the infected organs that were never procured because of concerns that no transplant center would take them.
Plus, “there are a lot more people dying with hepatitis C right now because of this God-awful increase in opioid abuse,” said Reese. (The vast majority of new hep C infections are attributed to injection drug use.)
“If it was me who needed a kidney, I would sign up for this.”
Dr. Christine Durand, Johns Hopkins University
Reese and other proponents of the new approach say the major obstacle now is funding — and cost concerns abound, given that a course of the latest hepatitis drugs runs anywhere from $54,500 for Zepatier to $94,500 for Gilead Sciences’ Harvoni. That’s on top of the hundreds of thousands in medical costs associated with the transplant itself and the needed immune-suppressing agents.
There’s nothing legally prohibiting these kinds of transplants — unlike, say, for those that involve putting HIV-infected organs into HIV-negative patients. Yet, insurance companies might balk at the idea of intentionally exposing patients to a deadly virus and then paying for the pricey pills needed to keep the infection at bay.
The trials are designed, in part, to convince insurers and the medical community that these kinds of transplants are safe, effective, and perhaps money-saving.
With one year of dialysis costing about $70,000 on average, most experts anticipate that the transplant and drug therapy will be the cheaper option in the long run, although a formal cost-analysis has not been conducted.
Dr. Brian Pereira, whose research 25 years ago first showed that hep C can be transmitted via organ transplantation, leading organ banks to impose bans, said he is buoyed by the opportunity to make use of these kidneys again. The number of people who will benefit may be small compared with the total number of kidney transplants from deceased donors in the United States, which topped 12,000 last year.
But, with “so many people on the list, we need to do everything possible to bring more donors into the pool,” said Pereira, now president and CEO of Visterra, a drug company in Cambridge, Mass. “And it if can be done safely, it’s terrific.”