Each year in the United States, an estimated 1000 patients die while waiting for heart or lung transplantation. Otherwise viable organs from donors infected with hepatitis C virus (HCV) have typically not been transplanted because of high rates of HCV transmission (up to 82% of recipients), associated mortality from liver disease, and other complications associated with HCV infection.1
However, the availability of direct-acting antivirals (DAAs) for HCV treatment “has raised the possibility of substantially increasing the donor organ pool by enabling the transplantation of hearts and lungs from HCV-infected donors into recipients who do not have HCV infection,” according to Harvard researchers who conducted an open-label trial reported in April 2019 in the New England Journal of Medicine.1
To that end, they investigated the transplantation of lungs (n=36) and hearts (n=8) from HCV-infected donors to uninfected adult recipients with advanced lung or heart failure at Brigham and Women’s Hospital in Boston, Massachusetts. Immediately after transplantation, a detectable HCV load was observed in 42 of the 44 recipients. Prophylactic daily administration of the DAA regimen sofosbuvir (400 mg)/velpatasvir (100 mg) was initiated a few hours posttransplant and continued for 4 weeks.
Of the total sample, 35 patients completed ≥6 months of follow-up, at which point all “were alive and had excellent graft function and an undetectable hepatitis C viral load,” as stated in the paper. The patients’ “viral load became undetectable by approximately 2 weeks after transplantation, and it subsequently remained undetectable in all patients.”
Of the 16 recipients with follow-up data at 12 months posttransplant, there was a 94% graft survival rate. (One heart transplant patient died from a bacterial infection that was determined to be unrelated to HCV infection.) None of the patients experienced serious adverse events related to DAA treatment.
“In our trial, hearts and lungs from HCV-infected donors were transplanted safely with excellent graft function at 6 and 12 months,” the authors concluded. “However, longer-term data are needed to fully define the risk-benefit profile.”
Pulmonology Advisor checked in with the following experts to learn more about the implications of these findings: Gundeep Dhillon, MD, MPH, medical director of the Heart-Lung & Lung Transplantation Program at Stanford Health Care and associate professor in the Department of Pulmonary and Critical Care Medicine at Stanford Medicine in California; Bryan Whitson, MD, PhD, cardiothoracic surgeon and associate professor of surgery at the Ohio State University Wexner Medical Center in Columbus; Marie M. Budev DO, MPH, FCCP, medical director of Cleveland Clinic’s Lung and Heart-Lung Transplant Program in Ohio; Errol L. Bush, MD, FACS, surgical director of the Johns Hopkins Advanced Lung Disease and Lung Transplant Program and assistant professor of surgery at the Johns Hopkins University School of Medicine, Baltimore, Maryland; and Christine Durand, MD, associate professor of medicine and oncology at Johns Hopkins and an expert on infectious disease and organ transplantation in persons living with HIV and HCV.
Pulmonology Advisor: What are the current guidelines for testing blood-borne diseases before transplantation?
Dr Dhillon: Current Organ Procurement and Transplantation Network policy2 requires deceased donor testing for the following infections:
- Hepatitis B virus (HBV)
- Epstein Barr virus
The organ procurement organizations and transplant centers might pursue testing for other infections based on clinical picture or local factors; for example, blood cultures for bacterial infections, testing for West Nile virus, and so on.
Dr Whitson: The standard of care is that all donors are tested for HIV, HBV, and HCV antigen and nucleic acid before recovery. There are a handful of donor behaviors, such as intravenous drug use and incarceration, that would place the donor at increased risk of being a carrier. If the donor has exposure within ~5 days of testing, there may be false negatives.