More than 97,000 people in the United States are currently awaiting kidney transplants—waits that can often take five or more years.
Two Perelman School of Medicine faculty members recently released findings from a clinical trial that could lead to about 1,000 more kidney transplants each year.
The research, led by David Goldberg and Peter Reese, both assistant professors of medicine and epidemiology, shows that 10 patients’ lives were saved with kidney transplants from deceased donors infected with the Hepatitis C virus.
The trial was launched in June of 2016, and is testing the effect of transplanting kidneys with the disease into patients who do not have Hepatitis C (HCV). By demonstrating that it’s possible to eradicate HCV from patients who contract the virus from a transplant, researchers say this could open up access to more donor organs currently being discarded—and hopefully lessen the amount of time some patients wait for organs.
Kidneys with HCV are traditionally discarded because they have been thought to be too damaged or high-risk, explains Goldberg. In addition, medication previously used to treat HCV came with numerous side effects—meaning a cure wasn’t necessarily guaranteed for transplant patients who received kidneys with the disease.
“Our pilot data demonstrate the ability to cure the contracted virus following transplantation in this patient population,” says Goldberg, who is also the medical director for Living Donor Liver Transplantation at the Hospital of the University of Pennsylvania (HUP). “If future studies are successful, this may be a viable option for patients who may otherwise never see a transplant.”
Reese says that patients who were willing to participate in the trial received high-quality kidneys.
“Over time, David and I have come to believe that just because the donor has Hepatitis C, their kidney quality may not be impaired, especially if you can cure the virus,” says Reese, also an assistant professor of medical ethics and health policy, and chair of the Ethics Committee for the United Network of Organ Sharing. Because the disease exerts its effects very slowly, it’s possible that a young donor or someone in the early stages of the disease may have very few health problems that result from HCV, meaning those kidneys are high-quality.
To enroll participants in this phase of the trial, Goldberg and Reese reached out to patients who relied on dialysis treatments, and who had been waiting for new kidneys for no more than a year and a half. Dialysis treatments, says Reese, are incredibly time-consuming, usually occurring three times a week and taking up to a half day each session.
Going into the study, Goldberg and Reese knew that, if unsuccessful, some or all of the patients would not only contract HCV, but have the disease for the rest of their lives. But a greater motivator for many who opted to participate was the chance to live a life without a need for dialysis.
“The more we talked to patients, many of them accepted the unknown to get a chance of getting their freedom back,” says Reese. “[We learned] that a lot of patients were willing and interested, and not nearly as worried or didn’t nearly associate Hepatitis C with the stigma.”
Interested participants underwent a rigorous process of education and consent before the transplants, and researchers made sure patients understood all of the risks.
The 10 patients in this first phase received their transplants, on average, 58 days after enrolling (the wait time ranged from 11 to 100 days). Three days after surgery, patients were tested for HCV; all 10 tested positive. Patients were then treated with Zepatier, a recently approved, highly effective oral medication, to cure the virus.
In addition to the key role played by the Gift of Life team, and Merck, which donated the drug, Goldberg and Reese say the participation of the Molecular Pathology Laboratory at HUP was critical. In the trial, researchers only used kidneys infected with a certain strain of the disease, HCV genotype 1, because it’s more susceptible to curing with Zepatier. Genotyping must be done shortly after kidneys become available—which means members of the lab had to be on call around the clock.
“That was a very special piece of doing this at Penn,” Reese says. “They’re heroes behind the scenes.”
After these positive results, Goldberg and Reese were granted an extension to the trial, which will enable them to transplant and treat an additional 10 patients.
The researchers are also designing a new clinical trial that will examine this same approach in patients who are awaiting heart transplants—and in the future, they hope to look at liver and lung transplants, as well.
Goldberg says, “We realized that the amazing transformation of treatment options for Hepatitis C should also transform how we think about organs with Hepatitis C.”