Ryan A. Helmick, MD
University of Tennessee Health Science Center
Methodist University Hospital

As the transplant community continues to search for a solution to the available organ shortfall, xenotransplantation remains a far-off promise and tissue engineered organs are in the earliest stages of research. Despite these challenges, the number of deceased donors has been increasing in recent years, due in large part to the opioid crisis. Between the years of 2010 and 2016, the number of deceased donors has increased overall by about 26%, while the number of donors who have died of a drug overdose has increased by 277%.¹ Often these donors are classified as PHS increased risk, and many have recent or long term infection from Hepatitis B virus (HBV) or Hepatitis C virus (HCV).

Utilization of organs from donors that are seropositive for HBV core antibody has long been considered acceptable at many centers, given the available therapies including Hepatitis B immunoglobulin as well as the antiretrovirals with a long history of successful HBV prevention. The lack of effective therapies for HCV has long limited organs from these donors only to patients who already have HCV. Some have reported positive results by utilizing the narrow subset of donors that are HCV antibody positive and RNA negative.² Yet in the current age of highly effective direct acting antiviral therapy, this way of thinking needs to be re-evaluated. The utilization of HCV positive organs for negative patients necessitates many ethical, financial, and medical questions be addressed in a thorough fashion, ideally by the entire transplant community.

The biggest hurdle in the utilization of HCV mismatch organs may relate to the ethical questions that arise from such transplants. Our medical school oath to “do no harm,” and the thought of knowingly “giving” someone HCV causes great hesitation; however, the transmission of cytomegalovirus (CMV) or Epstein Barr virus (EBV) in a seronegative recipient is rarely given a second thought. Treatment of CMV tissue invasive disease can be a significant though manageable challenge with severe cases causing morbidity and prolonged hospitalizations. Less frequently, EBV causes lymphomas necessitating chemotherapy and reductions in immunosuppression that can place the transplanted organs at risk of rejection. With the current state of treatment for HCV, patients receive a 12- to 24-week course of oral therapy that is often well tolerated with minimal side effects. De novo HCV infection almost never causes severe liver dysfunction, and with treatment response rates reported at 99-100% depending on the chosen direct acting antiviral regimen, post-transplant HCV should be a rather benign and easily treatable issue, especially when compared to PTLD or aggressive CMV. Given the treatability of HCV in the current era, use of these organs should flow from the basic tenets of medical ethics; with adequate informed consent, autonomous patients should have the option to proceed with these transplants.

The next tenet of medical ethics, beneficence, may be a trickier ethical question to address. The framing of the question should not merely revolve around “should this patient get an HCV+ allograft or not?” Rather, the issue is “should this recipient get an HCV+ kidney or remain on dialysis for another year or two?” or “should this low MELD recipient take an HCV+ liver or not get transplanted at all?” Bowring et al recently described the risks to kidney recipients who decline kidneys labeled as “PHS Increased Risk” in terms of delays in transplantation.³ What further gains might patients be able to realize in terms of decreases in dialysis time by opting for a HCV mismatched organ and going through treatment after transplant?

Once a program, surgeon, and patient are comfortable with the ethical issues regarding HCV mismatch, there are financial considerations to consider. While the early direct acting antiviral (DAA) therapies were reported to cost as much as $100,000, newer regimens are coming down in cost with estimates in the $25,000-35,000 range. When we compare these costs to the yearly costs associated with dialysis, earlier transplantation of kidney recipients might result in overall cost savings compared to waiting on dialysis for an HCV negative organ. Patients who are willing to accept HCV+ kidneys may be able to avoid dialysis altogether and realize the benefits of pre-emptive kidney transplant. As newer and more effective HCV therapies come to market and innovation and competition drive drug prices down, this will continue to be a more financially competitive option compared to years on dialysis.

Utilization of HCV mismatch organs is not likely to be a one-size-fits-all solution as it relates to medical suitability, including long wait times and donor shortages. Does it make sense to give a 30-year-old who has not yet started dialysis an HCV+ kidney? Would it make sense if the average wait time in that recipient’s region was eight years and he was not expected to do well on dialysis? What if instead he had steatosis and grade 2 fibrosis? There are certainly patients where HCV mismatch makes a great deal of sense; older diabetic patients without living donors in regions with long waiting times are prime candidates to use HCV+ kidneys. Similarly, patients with persistently low MELD scores can benefit from liver transplant with HCV mismatch livers and DAA therapy afterwards.  

The great efficacy that new DAA therapies for HCV have demonstrated has ushered in new opportunities for organ utilization. Given the rapidly increasing numbers of donors who are dying of drug overdose and who have HCV exposures, the transplant community has the opportunity and responsibility to utilize these organs for patients in dire need of lifesaving transplantation.

References

1. Chute DF, Sise ME. Effect of the Opioid Crisis on the Donor Pool for Kidney Transplantation: An Analysis of National Kidney Deceased Donor Trends from 2010-2016. Am J Nephrol. 2018;47(2):84-93. doi:10.1159/000486516
2. Nowak KM, Witzke O, Sotiropoulos GC, et al. Transplantation of Renal Allografts From Organ Donors Reactive for HCV Antibodies to HCV-Negative Recipients: Safety and Clinical Outcome. Kidney Int Rep. 2017;2(1):53-59. doi:10.1016/j.ekir.2016.09.058
3. Bowring Mary G., Holscher Courtenay M., Zhou Sheng, et al. Turn down for what? Patient outcomes associated with declining increased infectious risk kidneys. Am J Transplant. 2017;18(3):617-624. doi:10.1111/ajt.14577