BOSTON — After a preemptive short course of antivirals, recipients of heart and lungs from hepatitis C–infected donors went on to have “excellent” graft function at 6 and 12 months, with no detectable signs of the disease.
“I would say conservatively that this ability to safely transplant organs from hepatitis C–infected donors to uninfected recipients could increase the number of organs available for transplantation by about 20%,” lead author Ann E. Woolley, MD, told theheart.org | Medscape Cardiology.
“However, it’s a moving target because, unfortunately, the IV drug use epidemic continues and the percentage of donors that have hepatitis C is continuing to increase, many of whom have a history of active drug use.”
In a study published online April 3 in the New England Journal of Medicine, Woolley and a team of infectious diseases experts, transplant physicians, and surgeons at Brigham and Women’s Hospital, Harvard Medical School, Boston, reported findings from their open-label, pilot study.
Although transplants from donors with hepatitis C virus (HCV) have previously been done, the best approach for initiating treatment and the duration of treatment after transplant, as well as the outcomes for heart and lung transplant recipients, have not been systematically studied.
In 44 patients — 36 of whom received lung transplants and eight of whom received heart transplant — direct-acting antiviral treatment was initiated within hours of organ transplantation surgery. No patients received both organs.
Direct-acting antiviral treatments have revolutionized the field of HCV treatment. The drug regimens are usually given for 8 to 12 weeks and are expensive. The researchers employed an abbreviated 4-week course of sofosbuvir 400 mg and velpatasvir 100 mg once daily, with all medications provided by the study at no cost to the patients.
In the majority of cases, the viral load went down to zero within days, and in all patients, it was undetectable around the 2-week mark, Woolley and colleagues report.
HCV is transmitted not from a transplanted organ itself, but rather from the blood that comes along with the organ. “Even though the organs are washed out, there’s always some microscopic amount of blood remaining, and when that blood gets to the liver and sets up shop and starts replicating, that’s how the virus is transmitted.”
“Since we started treatment at time zero, as soon as was safe to do so after transplant, the recipients had very low viral loads and we were able to prevent the virus from getting to the liver and replicating,” explained Woolley, adding that their protocol demonstrates a potential for postexposure prophylaxis of hepatitis C.
The median viral load in the HCV-infected donors was 890,000 IU/mL, yet the median detectable viral load immediately after transplantation in 42 of 44 organ recipients with detectable HCV was 1800 IU/mL.
Because eradicating HCV from recipients of infected organs is only half the challenge, the researchers also assessed the safety of the transplanted organs and their longevity.
Of the first 35 patients enrolled who completed 6 months of follow-up, all were alive and had excellent graft function and an undetectable HCV load. In 15 of 16 organ recipients with 12-month follow-up data, outcomes were similar to those seen in recipients of hearts and lungs from donors not infected with HCV.
However, there were numerically more cases of acute cellular rejection for which treatment was indicated in the HCV-infected lung-transplant recipients compared with the patients who received lungs from uninfected donors.
“We didn’t see this in the hearts, and the difference was not statistically significant, but we wanted to make sure we highlighted this finding because, of course, we want to make sure there are no other noninfectious complications that can come of using this organ source,” said Woolley.
Still Much to Learn
In an accompanying editorial, Emily A. Blumberg, MD, University of Pennsylvania, Pittsburgh, writes: “The time has come to consider expanding the use of HCV-mismatched transplantation under controlled conditions.”
However, she also stressed the need for many more answers, some of which should be gleaned from larger-scale multicenter trials.
The unmet need is clear: there are currently more than 113,000 people on waiting lists for transplants in the United States, Blumberg said. In 2018, 36,500 people received transplants and 12,225 were removed from the waiting list either because of death or progression of illness that rendered them too sick for transplantation.
Among the questions still unanswered is whether the virologic response seen at 6 and 12 months will be sustained in the longer-term, and whether there might be an increased risk for cardiovascular disease in recipients, as has previously been reported in recipients of HCV-positive organs.
Also, she suggested that “patient consent assumes a level of understanding about HCV infection that may not currently exist.”
And then there is the issue of costs, with a 12-week course of sofosbuvir alone costing about $84,000 in the United States. It is unclear who will bear the burden of even an abbreviated course of treatment.
“The early results are very encouraging, but there is still a lot to learn,” said Blumberg, who like Woolley is a transplant infectious disease specialist. She is the current president-elect of the American Society of Transplantation.
This work was supported in part by the Mendez National Institute of Transplantation Foundation, Brigham and Women’s Hospital, and Grant number 1UL1TR002541-01, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science. Woolley and Blumberg reported no conflicts of interest.
By Debra L Beck