Each year in the U.S., some 500 kidneys are deemed ineligible for donation and are discarded because they came from deceased donors who are hepatitis C-positive. Transplanting these organs into recipients who are virus free has been generally considered too high risk, and only a tiny fraction of patients awaiting kidney transplant are infected with the virus. Now, a recent study led by Johns Hopkins suggests that direct-acting antiviral prophylaxis before and after transplantation could significantly alter the landscape of organ transplantation from hepatitis C-infected donors to noninfected recipients.1 In a study of 10 virus-free patients who received hepatitis C-infected kidneys, none developed clinical signs of chronic hepatitis C infection in the three months following surgery, and all have continued to remain free of the infection.
New hepatitis C treatments pave the way
Over the last decade, the treatment of hepatitis C has undergone a major transformation, propelled by a generation of new drugs that are more potent and cause fewer side effects. Now, a disease that was previously difficult to treat—requiring weekly injections of drugs with significant toxicities for many patients—and quite challenging to cure, can be treated with drugs that carry few side effects and result in cures for the vast majority of patients.
This paradigm shift led Johns Hopkins physicians Niraj Desai and Christine Durand to explore whether the new hepatitis C drugs—known as direct-acting antivirals (DAAs)—could also be used to improve the utilization of hepatitis C-positive kidneys for transplantation. “In this era of organ shortages, it’s difficult to watch good organs get discarded,” says Durand. “This was a great opportunity to take a neglected public health resource and put it to good use.”
Proof-of-principle study yields dramatic results
Desai, Durand and their colleagues launched an open-label, nonrandomized trial at Johns Hopkins known as EXPANDER (Exploring Renal Transplants Using Hepatitis C Infected Donors for HCV-Negative Recipients). The team recruited patients over the age of 50, who lacked a living donor and were awaiting kidney transplant, had no history of organ transplant, and were negative for hepatitis C as well as HIV and hepatitis B. Ten patients agreed to participate, with an average age of 71 and an average time on the transplant wait list of four months.
Donor kidneys were recovered from deceased donors ranging in age from 13 to 50. The organs tested positive for hepatitis C and showed no evidence of kidney disease. Donor blood was also analyzed to determine the strain and levels of hepatitis C virus. “These 10 kidneys we used are 10 kidneys that would not have been transplanted outside of this study,” says Desai. “They would have been discarded.”
To provide prophylaxis for hepatitis C, each kidney recipient received a dose of grazoprevir/elbasvir, an oral combination pill, prior to transplant surgery. Following transplant, recipients continued with daily grazoprevir/elbasvir therapy for 12 weeks. Three patients also took a daily dose of sofosbuvir due to the strain of virus found in their donor organ.
In five of the kidney recipients, no hepatitis C RNA could be detected in their blood. In the other patients, low levels of the virus were detected shortly after transplant but then became undetectable within days or a week. Importantly, none of the recipients ever developed any clinical signs of chronic hepatitis C infection, and the kidneys functioned well. At the time of the study’s online publication in the Annals of Internal Medicine, all patients were at least a year post-transplant and remained healthy and hepatitis C-free.
Looking ahead
Desai and Durand are deeply encouraged by the EXPANDER trial’s results. They seek to extend their initial findings through a larger, multicenter trial. If this early success continues, it could propel the availability of more organs for the nearly 100,000 people in the U.S. now waiting for a kidney transplant. In addition, this novel approach could be expanded to other organs, including the heart, liver and lungs.
“Right now, most of the usable organs from donors with hepatitis C are discarded,” says Desai. “Figuring out how to use these kidneys is a way to do more transplants and save more lives.”
References
1 Durand CM et al. Direct-Acting Antiviral Prophylaxis in Kidney Transplantation from Hepatitis C Virus-Infected Donors to Noninfected Recipients. Annals of Internal Medicine. Published online March 6, 2018.