SAN FRANCISCO – Preliminary data from a new study presented this week at The Liver Meeting® – held by the American Association for the Study of Liver Diseases – found that pre-emptive administration of pan-genotypic, direct-acting antiviral therapy prevents chronic hepatitis C virus infection in hepatitis C-negative cardiac transplant patients who receive donor hearts infected with the virus.
Hepatitis C virus, commonly called HCV, is a liver disease that ultimately can cause cirrhosis (scarring of the liver), liver cancer and liver failure. HCV is mainly contracted when a person comes in contact with an infected person’s blood.
Cardiac transplants are limited in the United States due to an increasing lack of available donor hearts. While heart failure cases rapidly rise in the U.S., the number of annual heart transplants has remained the same for the last 10 years. A significant number of donor hearts are discarded because, although they meet the standard criteria for donation, these organs are infected with HCV.
Researchers at Massachusetts General Hospital in Boston conducted a study to explore whether preemptive, pan-genotypic, DAA treatment could prevent chronic HCV infection in HCV-negative cardiac transplant patients who receive HCV-infected donor hearts.
“In UNOS (United Network for Organ Sharing) Region 1, almost a quarter of hearts meeting standard criteria for cardiac donation were discarded based solely on HCV positivity in 2016,” explains Emily D. Bethea, MD, fellow, Liver Center and GI Division at Massachusetts General and the study’s first author. “As the shortage of transplant viable organs persists, it is of paramount importance that all potentially transplantable organs are identified. If DAAs can successfully prevent the development of chronic infection in recipients of HCV-positive organs, then we could make available an underutilized resource.”
Twenty-five patients were enrolled in this single-center, proof-of-concept trial. Their status on a cardiac transplantation waitlist was updated to reflect their willingness to accept an HCV-positive donor heart. If an enrolled patient received an offer for an HCV nucleic-acid testing-positive (or NAT-positive) donor heart, they received pre-emptive treatment with glecaprevir-pibrentasvir. Their first dose of the antiviral therapy was administered before they were transported to the operating room for transplant. After surgery, each patient then completed eight weeks of treatment. HCV viral load monitoring was performed during and after treatment to ensure adequate viral suppression and no detectable HCV virus in the blood for 12 or more weeks after competing treatment (called sustained virologic response).
So far, 16 patients in the trial have received an HCV-positive donor heart. All achieved viral suppression with undetectable or non-quantifiable HCV RNA by the ninth day after their transplants. All HCV RNA tests after initial viral suppression have remained undetectable. There have been no drug-related side effects or interactions that led to lapses or stopping of therapy. There have been no treatment failures. To date, cardiac allograft and patient survival is 100 percent over 1,740 cumulative days of follow-up.
“Our study demonstrates the success of preemptive DAA therapy in cardiac transplantation. We believe this novel approach can help to increase the donor pool, decrease heart transplant wait times, and improve health outcomes,” says Dr. Bethea. “With the rising number of HCV-positive donor organs, there is a time-sensitive and critical need to document both efficacy and detailed implementation strategies surrounding the successful use of HCV-positive organs.”
Editor’s note: This press release contains updated data that is not reflected in the published abstract, but will be presented at The Liver Meeting®.
Dr. Bethea will present the study entitled “Preemptive Pan-Genotypic Direct Acting Antiviral Therapy in Donor HCV-Positive to Recipient HCV-Negative Cardiac Transplant” will be presented on Sunday, November 11 at 10:30 AM in Hall D. The corresponding abstract (number 0007) can be found in the journal, HEPATOLOGY.