DONATE-HCV trial offers new hope to those on waiting lists for new hearts and/or lungs.
Even though hepatitis C virus (HCV) is now imminently treatable with direct-acting antivirals (DAAs), and even though an entire generation of Americans—namely the Baby Boomers—are considered to be at increased risk of infection (due to blood transfusions in the 1950s and 1960s), there remains a definitive stigma surrounding the disease.
And, sadly, like most social stigmas, there are downstream effects—in this case, a reluctance on the part of some with the disease to confirm diagnosis and receive treatment. Unfortunately, HCV has also become a key component of the ongoing opioid abuse epidemic currently engulfing the United States.
Now, though, the results of a new study called DONATE HCV, published in New England Journal of Medicine (NEJM), may go a long way toward removing some of the stigma surrounding the disease, while opening up whole new opportunities for those in need of heart and/or lung transplants. That’s because the study found that transplant patients who receive organs from donors with the virus are safe from infection if prophylactic antiviral therapy is administered for 4 weeks postoperatively.
“The findings from our DONATE HCV Trial are exciting since it demonstrates that not only can we prevent the establishment of hepatitis C in the transplant recipient when transplanting an organ from a donor with active HCV using a shortened, 4-week course of preemptive HCV treatment, but that also the 6-month and 12-month outcomes including graft survival and overall survival were no different compared to the transplant recipients at our center who received organs from donors who were not HCV-infected,” study co-author Ann E. Woolley, MD, an instructor in medicine at Harvard Medical School and an infectious disease specialist at Brigham & Women’s Hospital in Boston told Contagion®. “We hope the findings from our trial, as well as data that are emerging from other centers, will decrease the stigma [surrounding HCV] and lead to fewer organs, which are otherwise medically suitable, being unnecessarily declined just because the donor has HCV.”
Historically, of course, organs from donors with HCV have been rejected for fear of transmitting the virus to already immunocompromised recipients. Although more than 35,000 organ transplants are performed in America each year (roughly 10% involve the heart or lungs), according to US Department of Health and Human Services figures, roughly 20 people die each day waiting for a donor organ. Simply put: The fewer organs that are rejected, the better.
Perhaps because of these stark statistics, the findings of the DONATE HCV study have garnered significant attention from the mainstream media.
For the study, Woolley and colleagues enrolled 44 patients (36 lung, 8 heart) who received organs from donors with HCV. The outcomes within this patient population were compared with those in a similar cohort of patients who received organs from un-infected donors.
All 44 patients in the study were preemptively administered the DAA sofosbuvir-velpatasvir for 4 weeks, beginning within a few hours after transplantation, to block viral replication. According to the NEJM report, median viral load in the HCV-infected donors was 890,000 IU per milliliter and 61% of the donors had HCV genotype 1, while 17% each had genotypes 2 or 3 (the remaining 5% had indeterminate genotype).
In all, 42 of 44 recipients had detectable hepatitis C viral load immediately following transplantation, with a median of 1800 IU per milliliter. Of the first 35 patients enrolled who had completed 6 months of follow-up, all were alive and had excellent graft function and an undetectable hepatitis C viral load. In fact, according to the investigators, HCV viral load was undetectable in these recipients within approximately 2 weeks following transplantation. No treatment-related serious adverse events were identified. More cases of acute cellular rejection for which treatment was indicated occurred in the HCV-infected lung-transplant recipients than in a cohort of patients who received lung transplants from donors who did not have HCV infection. This difference was not significant after adjustment for possible confounders.
“The DONATE HCV Trial is the largest prospective HCV thoracic organ transplantation study to date,” Woolley told Contagion®. “HCV treatment is currently very expensive. Our approach of using a shortened, preemptive 4-week course of HCV direct-acting antivirals is much less expensive and yet was 100% effective. Therefore, ours is an approach that can be adopted by other centers.”
In a related commentary published in the same issue of NEJM, Emily A. Blumberg, MD, director of Transplant Infectious Diseases at the University of Pennsylvania Medicine, noted that “this trial has some unique features that must be considered. The median donor age was surprisingly young, and HCV-positive donors were younger than those without HCV infection. Both HCV-negative and HCV-positive donors in this trial were younger than the mean age in the current donor pool in the United States. As anticipated, the availability of HCV-positive organs resulted in transplantation in candidates who were less critically ill and who had a lower priority on the waiting list for transplantation. Consequently, the shorter lengths of stay in the intensive care unit and hospital and the relative preservation of renal function probably reflect recipient factors rather than donor factors. Whether longer-term results will be equally encouraging is unknown.”
Notably, the findings of the DONATE HCV study echo those of earlier research involving kidney transplant recipients. In fact, researchers at the University of Miami Miller School of Medicine presented positive outcomes with organs from HIV/HCV-coinfected donors in a study published in the journal Clinical Transplantation in March.
“We focused the first phase of our study on heart and lung transplants given the shortage of organs that exists despite the significant need in this patient population for transplants,” Woolley said. “We are planning to include kidney transplant recipients and dual organ transplant recipients in the second phase of our study.”
The team will also be experimenting with “an even shorter HCV treatment course” in their future work. Perhaps by then, there won’t be a stigma surrounding the virus anymore.