Proof-of-concept study follows patients who receive a HCV-positive donor heart.
Emily Bethea, MD
In an effort to increase the amount of donor hearts available, investigators are looking at whether hearts from hepatitis C virus (HCV) infected donors can be safely transplanted.
A team, led by Emily Bethea MD, Harvard Medical School, recruited 55 patients enrolled in a heart transplantation list in an open-label, single-center, proof-of-concept study from Nov. 1, 2017 to Nov. 30, 2018.
After agreeing to participate in the study, each patient’s status on the heart transplantation list was updated to reflect their willingness to accept either an HCV-positive or HCV-negative donor heart.
The patients who underwent heart transplantation with a viraemic donor heart—which was determined by nucleic acid testing (NAT)—received pre-emptive oral glecaprevir-pibrentasvir therapy (SVR12) prior to being transported to the operating room. They then were given an 8-week course of glecaprevir-pibrentasvir after the heart transplantation.
Some patients received HCV antibody-positive donor hearts without detectable circulating HCV RNA. These patients were followed using a reactive approaching, starting glecaprevir-pibrentasvir if they developed viraemia.
“The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12),” the authors wrote.
Of the 55 patients, 52 consented to enrollment, 25 underwent heart transplantation with a HCV-positive donor heart—20 NAT-positive and 5 NAT-negative—3 of which underwent a simultaneous heart and kidney transplantation.
The patients must be at least 18 years without a history of liver disease to participate in the study.
The 20 recipients of the NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression with a median clearance time of 3-5 days. All 20 patients subsequently achieved SVR12.
The 5 patients who received NAT-negative grafts also did not become viraemic.
The median pre-transplant waiting time for patients following enrolment in the transplant list in the HCV protocol was 20 days and patients and allograft survival rates was 100% following a median follow-up of 7-10 months. The long-term outcomes are not yet known.
“Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts,” the authors wrote.
The patients were followed from the time of their enrollment in the study to 1 year after transplantation. The study represents an interim analysis, initiated after all of the enrolled patients reached the primary outcome.
There currently is a global need for all potentially transplantable organs, including hearts. However, a major concern remains the development of HCV infections in previously uninfected recipients of HCV-infected donor hearts.
There are more than 113,000 people in the US on the organ donor list, the majority of which are waiting to receive a kidney. According to the US Government Information on Organ Donation and Transplantation, 36,528 transplants were performed in 2018 with 20 people each day dying while waiting for a transplant.
However, a 2018 report shows that direct-acting antiviral drugs could help cure HCV in greater than 90% of cases, making the risk of infection both manageable and ethically acceptable.
The study, along with the current proof-of-concept study, was funded by the Massachusetts General Hospital.
The study, “Pre-emptive pangenotypic direct acting antiviral therapy in donor HCV-positive to recipient HCV-negative heart transplantation: an open-label study,” was published online in Gastroenterology & Hepatology.