Continuing to Blaze New Trails in Transplantation: First Kidneys, Now Hearts

In April 2017, in a groundbreaking clinical trial, physicians transplanted kidneys infected with the hepatitis C virus (HCV) into 10 patients on the transplant waitlist, then successfully destroyed the disease in all the recipients, using a recently approved, highly effective oral medication. But that pilot study was just the first step for this innovative approach that stands to dramatically increase the number of available transplant organs. Since then, 10 more patients have received HCV-positive kidneys, and most recently, 10 received HCV-positive hearts—with encouraging results.

The kidney transplant trials were co-led by Peter Reese, MD, MSCE, and David Goldberg, MD, MSCE; Rhondalyn McLean, MD, MHS, co-led the heart transplant trial with Drs. Reese and Goldberg.

As of August 2018, a total of 20 patients at Penn Medicine had been cured of HCV following kidney transplants from deceased donors infected with the disease. The research team reported full data from this trial, which included 12-month HCV treatment outcomes in the first 10 patients and six-month outcomes in the second 10. They found that kidney function in these 20 recipients was similar to that of patients who received kidneys from donors without HCV. 

The idea of using such organs was further supported in February 2019, when another study reported that nine Penn Medicine patients had been cured of HCV following heart transplants from donors infected with the disease. The researchers had modeled the heart-transplant trial, known as USHER, after the earlier study on transplanting HCV-infected kidneys, which was known as THINKER. In both, after receiving HCV-positive organs, patients were treated with the antiviral elbasvir/grazoprevir, commonly known as Zepatier.

The heart transplant study enrolled candidates who, like the kidney transplant patients, faced lengthy wait times – often five, seven, or even 10 years. During the pre-enrollment phase, the researchers conducted a three-step process of education and informed consent to ensure that participants and their loved ones understood the potential risks. The team then used specific criteria to evaluate available organs; these included a genotype restriction intended to minimize risk.

Ten patients received transplants using the protocol. All 10 tested positive for HCV. The team then treated them with a 12-week course of the antiviral medication, and all 10 responded rapidly. While the presence of HCV and use of antiviral therapy did not cause any adverse events, one patient died due to complications of antibody-mediated rejection in the first three months following transplantation. The other nine were cured of their HCV and reported good quality of life.

The researchers noted that this was the first trial in thoracic surgery to transplant hepatitis C-infected hearts into hepatitis-C negative patients with a formal protocol, which made it possible to collect detailed prospective data from the donor and recipient. The team was able to identify novel data on viral replication and clearance in heart recipients in the USHER trial, as well as in the kidney recipients in the THINKER trial.

“For decades, most hepatitis C-infected hearts were discarded – and the few people who received these organs were found to have a significantly lower rate of survival,” said Dr. Reese. “Our heart-transplant trial provides fresh evidence to show that new antiviral treatments for HCV work well in immunosuppressed patients, which has the potential to really impact the field of transplantation. These preliminary results suggest that we should make it a priority to expand the use of good-quality HCV-infected organs.”