A Counterintuitive Cure: Transplanting HCV-Positive Kidneys into HCV-Negative Recipients for End-Stage Renal Disease at Penn Medicine


Kidney diagram with partial definition

In 2016, clinician researcher Peter Reese, MD, MSCE, and colleagues at the Penn Transplant Institute reported the results of THINKER, a small study in which, for the first time, hepatitis C-positive (HCV+) kidneys were transplanted into uninfected recipient. Dr. Reese is an associate professor of Medicine and a nephrologist at the Penn Transplant Institute.

First proposed in the 1990s as an option for HCV+ recipients, the transplantation of hepatitis-bearing kidneys into uninfected persons had to wait until an effective cure for HCV evolved. That cure arrived in 2014 with the FDA approval of Harvoni, an effort due in part to the research of hepatologist Rajender Reddy, MD, at the Perelman School of Medicine.

HCV+ Kidneys for HCN-negative Transplant Recipients

For patients with end-stage kidney disease, the appeal of transplantation with an HCV-infected kidney, should the disease be curable, is that of avoiding prolonged dialysis (ironically, a major source of HCV infection) and a protracted wait for a disease-free kidney. As of this writing, the population in the United States awaiting kidney transplant exceeds 100,000, with an average wait time of 3.6 years.

Implanting diseased kidneys into non-diseased recipients seems counterintuitive, of course, in part because transplant recipients have a higher than normal risk of infections a result of the immune-suppressing drugs they take to prevent transplant rejection.

For this and other reasons, the Kidney Donor Profile Index (KDPI) Calculator continued to assign worse risk scores to organs from HCV+ donors as recently as 2019. In that year, Dr. Reese challenged the KDPI using national United States registry data to show excellent kidney function at 12-months post-transplant in HCV-viremic kidney recipients.

The transplantation of HCV+ kidneys into HCN-negative recipients works because the risk of deleterious HCV infection can be eradicated by an evolving set of antiviral drug regimens. In the original trial of 10 patients at Penn, all patients were cured of HCV, and all had successful transplants.

The principle risk, infecting others in the patient's family or contacts, can be managed with careful hygiene and the now familiar isolation and distancing procedures.

The First Multi-center HCV+ Kidney Transplant Study

Small, individual facility trials can reveal the promise of an approach, but a multi-center study is generally required to determine whether the findings of these trials are generalizable to larger, more demographically distinct populations. Thus, it was welcome news when the first multi-center HCV+ kidney transplant study was reported in the Journal of the American Society of Nephrology in August 2020.

The study, which contained patient data from Penn Medicine, was co-authored by Dr. Reese, who led the transplant activities at Penn Medicine and coordinated data collection for the study team with principle investigators Raymond Chung, MD and Meghan Sise, MD of Massachusetts General Hospital.

The MYTHIC Study

Known as MYTHIC (Multicenter Study to Transplant Hepatitis C–Infected Kidneys), the study involved the transplantation of HCV-infected kidneys into 30 HCV-negative individuals. Of the 30, most of whom were on dialysis—the median wait-time for transplant was only about six weeks after consenting to receiving an HCV-positive kidney.

Shortly after transplant, the recipients were treated with a standard combination of anti-HCV drugs, glecaprevir/pibrentasvir.

As with the THINKER trial, the research team found that when tested, 12 weeks after finishing drug treatment, recipients in the MYTHIC trial had undetectable levels of HCV genetic material on sensitive blood tests; none experienced severe adverse events associated with the antiviral treatment, or from HCV. Overall allograft function at 6 months was excellent. 

“Being able to make use of these HCV-positive kidneys from relatively young and otherwise healthy donors should improve current wait times for would-be recipients and has real potential to improve quality of life,” Dr. Reese said in a recent interview, adding that Penn intends to do more studies of this kind in an effort to save more lives and, hopefully, "make the approach a standard of care." 

Other Penn Medicine researchers involved in the study were Douglas Schaubel, Stacey Prenner, Richard Landis, Melissa Fernando, and Caitlin Phillips. Many members of the Penn Transplant Institute provided clinical care and support to the MYTHIC patients during their recovery from transplantation.

THINKER-NEXT Study: Enrolling Soon

The Transplanting Hepatitis C Kidneys into Negative KidnEy Recipients [THINKER-NEXT] study will soon be enrolling at Penn Medicine.

This trial will include adult kidney transplant candidates without hepatitis C virus (HCV) infection on the transplant waiting list who will consent to kidney transplantation from a deceased donor infected with HCV, followed by treatment with a direct acting antiviral.

The one-year allograft function and one-year risk of CMV infection will be compared between THINKER-NEXT kidney transplant recipients and matched recipients who received hepatitis C uninfected kidney transplants (these patients are called Transplant Cohort). The mortality rate of kidney transplant candidates who enroll in THINKER-NEXT and consent to offers of kidneys from HCV-infected donors will be compared to matched wait-listed patients who do not consent to receive HCV-infected kidneys (these patients are called Wait-list Cohort).

Lastly, renal pathologic findings will be compared among HCV-viremic donors and HCV-negative comparator donors.


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The Penn Physician Blog is a resource for health care professionals featuring Penn Medicine physicians and their research, innovations, programs and events. 

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