Dr Budev: In addition to screening all donors for HIV, HCV, and HBV by serology, many brain-dead donors will have bronchoscopy, chest radiograph, and/or computerized tomography scans looking for infection, along with bronchoalveolar lavage and blood and urine cultures.
Pulmonology Advisor: Will the results from this trial make it possible for more organs to be available for transplant?
Dr Whitson: Yes, if the cost of the treatment drugs can be covered.
Dr Dhillon: The results of this trial offer reassurance that thoracic organs from HCV-infected deceased donors can be transplanted without any apparent adverse events in first 6 months, as long as the recipients receive an effective antiviral regimen in the immediate postoperative period.
The results of this trial, which were presented at the 2019 International Society for Heart and Lung Transplantation meeting in Orlando, Florida, make it likely that more thoracic organs from HCV-infected donors will be used. Our analysis of the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients database suggests that there are likely more than 55 HCV-infected lung donors each year in the United States.
Dr Bush: The results of the trial will not directly increase the number of available donors, but the results do encourage organ procurement organizations and transplant centers to consider offering and accepting, respectively, HCV-infected donors that may not have otherwise been considered. Several centers, including Johns Hopkins, already have protocols in place to accept organs on the behalf of recipients, but as the practice becomes more commonplace, access to these organs will be less disparate and will more uniformly decrease waiting time.
Dr Durand: Generally speaking, the emerging evidence shows it is feasible and safe to transplant organs from HCV-infected donors into HCV-uninfected recipients. This practice is expanding the available organs for the more than 100,000 individuals waiting for a life-saving transplant.
Dr Budev: The scarcity of donor lungs is a significant factor contributing to respiratory death while awaiting lung transplantation. The average wait list mortality rate in the United States in 2015 was 16.5 deaths per 100 wait list years.3 Current practice for the use of HCV-infected donor lungs has been to use them only for HCV-positive recipients, although this has not been broadly adopted by all centers.
Pulmonology Advisor: What are the overall risks? Is it better to get HCV from a donor than to not receive the transplant?
Dr Dhillon: The overall long-term risks of HCV-infected organs remain unclear at this time. The risks, including relapse of HCV infection, as well as immunologic consequences, such as acute and chronic rejection risks, need to be defined. In severely ill patients or patients with rapidly progressive lung diseases, it is likely better to get the transplant and live with potential consequences of HCV infection.
Dr Whitson: That is an ethical debate. In general, HCV should be treatable, although if the recipient is not treated or does not get cured or incurs excessive cost, this becomes more of a gray area. Unfortunately, we do not have dialysis or ventricular assist devices for patients with lung failure.
Dr Bush: The benefit of strategies, such as the utilization of HCV-infected donors, that increase donor pool availability is that people will be transplanted earlier and presumably at a healthier stage than if they had remained on the wait list, where they could continue to have progressive chronic lung disease, become too sick to safely undergo transplant, or even die while waiting on the wait list.
Although antiviral medications today are quite effective against HCV infections/transmissions, there is a small risk that a virus will not be effectively controlled. However, as demonstrated in the trial and in our own limited experience, the recipients of these organs thus far have had clearance of their viral disease with good early outcomes and function.
Dr Durand: In all studies reported to date, transplant recipients have been cured of HCV acquired from the donor organ and have had good outcomes overall. Adverse events from the HCV or treatment have been extremely rare.
Dr Budev: The risks are few; therefore, it is more important to possibly acquire and be treated for HCV rather than die on the list waiting for a transplant. The risks include an increasing viral load leading to hepatitis, inability to orally take the medication, resistance of the virus to the drug, and minor risks including nausea, emesis, and drug interactions that need to be avoided.
Pulmonology Advisor: What are additional research needs in this area?
Dr Dhillon: Additional studies are needed regarding the following topics:
- Long-term risks and clinical outcomes
- Effect on immune system and potential modifications to standard posttransplant immunosuppression regimens
- Long-term adverse effects, if any, of antiviral medications in this population
Dr Whitson: Further research should focus on the efficacy of treatment, genotyping the HCV to specifically tailor therapy, and the risk to the transplant team and hospital staff and loved ones of the recipient because of the added HCV exposure risk.
Dr Bush: Although the trial is encouraging that short-term outcomes are protected despite transmission of the HCV infection, we do not have long-term data yet to demonstrate that these organs will have similar outcomes to their non-HCV-infected transplant counterparts. This will need to be evaluated in further and hopefully larger studies.
In the trial, medications were provided by the hospital; however, in clinical practice, these currently expensive medications may not be available in a prophylactic manner, and [there may be a] need to wait until the disease has been transmitted. Further patient advocacy is needed to ensure that recipients of these organs have access to the medications as early as possible, including in a prophylactic manner, if data continue to support its benefit.
Dr Durand: To date, most trials have been fairly small. Because this practice is new, we only know the short-term outcomes, and we need to learn more about whether there are associated challenges with this approach, such as increased risk for allograft rejection or other infections. There remains debate about the best way and time to treat the HCV; that is, is it better to prevent the infection by starting treatment before the transplant, such as some trials have done, or is it better to wait and treat after transplant? Hopefully, future studies will address these important questions.
Dr Budev: We need to find out when is the optimal time to give the DAA for HCV: immediately posttransplant? Or is it safe to wait?
We also need to see what immunological trigger the HCV has: Whether viremia occurs posttransplant, is it enough to lead to antibody-mediated rejection or other types of rejection?
We need to further study how else to eradicate the virus; for example, is ultraviolet light preimplantation on ex vivo lungs, similar to what they are doing in Canada, beneficial?4
We need to further study the cost of giving these drugs and how to lower them in the United States.
Pulmonology Advisor: Are there any additional clinical takeaways or other points you would like to mention about the topic?
Dr Budev: The donor pool continues to remain stagnant, and patients continue to die on the waiting list. We need to continue to look for ways to try to expand this pool safely, and this study does support this.
- Woolley AE, Singh SK, Goldberg HJ, et al; the DONATE HCV Trial Team. Heart and lung transplants from HCV-infected donors to uninfected recipients. New Engl J Med. 2019;380(17):1606-1617.
- US Department of Health and Human Services. Organ Procurement and Transplantation Network. Policies. https://optn.transplant.hrsa.gov/governance/policies. Accessed June 17, 2019.
- Abdelbasit A, Hirji A, Halloran K, et al. Lung transplantation from hepatitis C viremic donors to uninfected recipients. Am J Respir Crit Care Med. 2018;197(11):1492-1496.
- Cypel M, Galasso M, Ribeiro R, et al. A clinical trial evaluation the effects of ultra-violet C treatment (UVC) during ex vivo lung perfection (EVLP) as a method of inactivating hepatitis C infection in donor lungs. J Heart Lung Transplant. 2019;38(4):S53-S54.