Ten patients have been cured of hepatitis C virus (HCV) infection after undergoing kidney transplantation from deceased, HCV-positive donors, according to early data published by Penn Medicine in the New England Journal of Medicine. The findings are the result of a 2016 clinical trial that tested the effect of transplanting kidneys from donors with HCV into patients on the waitlist who did not have the virus but who opted to receive otherwise unused organs.
|For more Feature Articles on Hepatitis C, please click here.
After transplantation, the participants received antiviral therapy in an attempt to eradicate the virus.
The early data was also presented at the 2017 American Transplant Congress in Chicago by David S. Goldberg, MD, MSCE, Assistant Professor of Medicine and Epidemiology at the Perelman School of Medicine at Penn.
“We started this trial in the hopes that, if successful, we could open up an entirely new pool of donor organs, and effectively transplant hundreds, if not thousands, more patients who are awaiting a lifesaving organ,” said Dr. Goldberg, co-leader of the study. “Historically, Hepatitis C-infected kidneys were often discarded, and were thought to be damaged or too ‘high-risk.’ Our pilot data demonstrate the ability to cure the contracted virus following transplantation in this patient population. If future studies are successful, this may be a viable option for patients who may otherwise never see a transplant.”
Peter Reese, MD, MSCE, the other co-leader of the study, enrolled patients who were receiving dialysis. Participants had been waiting for a transplant for at least 1.5 years—ages ranged from 40 to 65 years of age.
To ensure the patients and their families were provided with a comprehensive understanding of the risks involved, a three-step process of education and consent was employed. After enrollment and as organs became available, the team performed HCV donor genotyping during the allocation process. Only kidneys that were considered “high quality” were selected.
Ten patients have received transplants using the protocol to date. On average, patients received a kidney 58 days after enrollment. Some received organs in as little as 11 days, while some waited more than 100.
On postoperative day 3, patients were tested for HCV—all 10 were found to be positive for the virus. They received a standard 12-week course of elbasvir-grazoprevir (Zepatier), a recently approved and highly effective oral medication for the eradication of HCV.
All 10 patients were cured.
“For so long, HCV was a virus with a very negative stigma associated with it, especially among physicians,” said Dr. Reese, who is an Assistant Professor of Medicine and Epidemiology at Penn, as well as the Chair of the Ethics Committee for the United Network of Organ Sharing (UNOS). “So it was interesting to see that patients were quick to jump at the chance to get this transplant, despite the possibility that they could get Hepatitis C permanently. Going into the study, we knew it was a possibility that some or all of the patients would contract HCV, and that they could have the disease for the rest of their lives if we were unsuccessful. But for these patients, getting off of dialysis and getting back to their normal lives was very much worth the risk.”
After reporting early encouraging results, the team was granted a study extension that will allow them to include 10 additional patients. A new trial is being developed to study this same approach in heart transplantation patients. The hope is to continue the work in patients receiving lungs and livers as well.
Authors note the need for longer and larger trials to evaluate the process in a broader population.
Additional contributors from Penn included experts from various disciplines, such as infectious disease, transplantation surgery, gastroenterology, hepatology, and pathology and laboratory medicine. The authors wish to acknowledge Drs. Deirdre Sawinski, Roy Bloom, Raj Reddy, Emily Blumberg, Jennifer Trofe-Clark, Vivianna Van Deerlin, Midhat Farooqi, Peter Abt, Matthew Levine, Paige Porrett, Susanna Nazarian, Ali Naji, Maureen McCauley, and Anna Sicilia.
The study is supported by a research grant from the Merck Investigator Initiated Studies Program. Merck also supplied the antiviral drugs used in the study.