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Recipients of HCV-positive hearts and lungs successfully treated with DAAs
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Study findings published today in The New England Journal of Medicine demonstrated the safety of transplanting hearts and lungs from hepatitis C-positive donors into HCV-negative recipients.
In the DONATE HCV trial, early antiviral treatment led to SVR at 6 months in 100% of HCV-uninfected patients who received an HCV-positive heart or lung, researchers reported.
“In the past, transplantation of organs from HCV-infected donors into uninfected recipients typically led to chronic HCV infections in the recipients, with HCV transmission to as many as 82% of the recipients,” Ann E. Woolley, MD, an infectious disease specialist at Brigham and Women’s Hospital in Boston, and colleagues wrote. “The development of potent direct-acting antiviral agents to treat HCV infection has provided an opportunity to treat this infection in patients who acquire it through organ transplantation, although the use of organs from infected donors has been controversial.”
Woolley and colleagues studied the outcomes of 44 HCV-mismatched heart (n = 8) and lung (n = 36) transplants at Brigham and Women’s Hospital. They administered sofosbuvir-velpatasvir to organ recipients for 4 weeks beginning a few hours after transplant. The researchers defined primary outcome as SVR at 12 weeks after completion of antiviral therapy and graft survival at 6 months after transplant surgery.
According to the study findings, the HCV-infected donors’ median viral load was 890,000 IU/mL and the infecting HCV genotypes were genotype 1 (61%), genotype 2 (17%), genotype 3 (17%) and indeterminate (5%). Immediately after transplant surgery, 42 recipients (95%) had a detectable hepatitis C viral load, with a median initial viral load of 1,800 IU/mL.
According to Woolley and colleagues, the first 35 patients who completed 6 months of follow-up were all alive, with excellent graft function and an undetectable viral load. They reported that the patients’ viral load became undetectable approximately 2 weeks after transplant and remained that way, and that there were no treatment-related serious adverse events.
They said “longer term data are needed to fully define the risk-benefit profile.”
“These exciting findings showed that by pre-emptively treating transplant recipients who received a thoracic organ from an HCV viremic donor a few hours after transplant, we could block viral replication of HCV in the recipient,” Woolley told Infectious Disease News. “This novel approach utilized a shortened, 4-week course of DAA treatment, analogous to post-exposure prophylaxis and achieved 100% success.”
In a related editorial, Emily A. Blumberg, MD, who specializes in transplant infectious diseases at the University of Pennsylvania Perelman School of Medicine, called the results “very encouraging” but said “there is still a lot to learn” when it comes to HCV-positive to -negative transplants.
“Data regarding long-term outcomes are limited; one of the longest follow-up periods reported is 1 year for 20 recipients. It is unknown whether an increase in the incidence of cardiovascular diseases, which was previously reported in recipients of organs from HCV-positive donors, will be a late complication,” Blumberg wrote.
She noted that the DONATE HCV trial guaranteed early antiviral treatment for organ recipients regardless of medical insurance coverage and that “most investigators have provided free direct-acting antiviral agents in the early period after transplantation.”
“These drugs are expensive, and it is uncertain who will bear that cost in nonresearch settings,” Blumberg wrote. “It is unknown whether cheaper short-course therapy, as used in the current trial, will be consistently effective in all recipients regardless of the organ transplanted and the timing of initiation of treatment. However, if the experience of Woolley et al. is borne out by other investigators, a short course of treatment would substantially reduce the cost of transplantation.
“To ensure prompt and equitable access to these potentially lifesaving organs, it is imperative that transplantation centers determine how antiviral agents will be provided in advance of acceptance of organs from HCV-positive donors.”
Blumberg noted that the highest incidence of HCV in the United Sates is among injection-drug users, and that a large proportion of organ donations come from these patients.
“The time has come to consider expanding the use of HCV-mismatched transplantation under controlled conditions. Increasing numbers of successful outcomes in single-center studies provide support for further research with larger scale multicenter trials,” she wrote. – by Bruce Thiel
References:
Blumberg EA. N Engl J Med. 2019;doi:10.1056/NEJMe1901957.
Woolley AE, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1812406.
Disclosures: Blumberg reports being a co-investigator on multiple single-center, investigator-initiated HCV trials involving kidney, heart and lung transplants for which she has not received any direct or indirect support, but for which the principal investigators have received research support from Merck. Woolley reports receiving grants from the Menendez National Institute of Transplantation Foundation during the conduct of the study. Please see the study for all other authors’ relevant financial disclosures.