By Brad Segal
In my last post I characterized how overdoses from the surging opioid epidemic have become the fastest-growing cause of mortality among organ donors. In this update, I raise one potential consequence with ethical and policy implications: so-called donor-derived infections. To be clear, I focus primarily on organ recipients as deaths from drug overdose, and drug addiction more broadly, should be prevented regardless of any implications for transplantation. With this in mind, consider how the population of injection drug users shoulders a heavy burden of HIV, hepatitis B (HBV) and hepatitis C (HCV) (Table 1). First I will focus on screening guidelines, and then will move on to transplantation of organs known to carry an infection.
Screening guidelines can help reduce the incidence of donor-derived infections, but the lab tests recommended in any policy must balance two potential concerns. First, lab tests have a rate of false negative results. Transplants of these organs will accidentally increase donor-derived infections. The policy question, then, is whether or not transplanting organs donated by individuals with higher risk of recent disease exposure will expose an unacceptable proportion of recipients to infection. This unintentional harm could undermine a duty of non-maleficence to organ recipients. Further complicating a potential screening policy is that the basic lab tests for HIV, HBV, and HCV detect the presence of human antibodies, which work well among a low-risk population, but antibodies might not appear in the blood until weeks after infection (Table 2).Recent infections are better detected by nucleic acid amplification (NAT) testing.To mitigate risk of infection,then, transplant screening policies should require a heightened level of surveillance among donors with a history of illicit drug use.
On the other hand, NAT tests carry a rate of false positive results, and so increasing the overall number of tests will cause transplant coordinators to unnecessarily discard more healthy organs. Hence, at the same time, policies should minimize excessive NAT testing to promote donor beneficence and justice in organ allocation.
Three years ago, the U.S. Public Health Service (PHS) released updated pre-donation screening guidelines to reduce donor-derived infections of HIV, HCV, and HBC (the first such update since 1994). The new guidelines recommend all donors—regardless of risk—undergo the basic antibody testing for HIV, HBV, and HCV prior to transplantation. In addition, the PHS recommends nucleic acid amplification (NAT) testing if donors are at “higher risk” of HIV, HBV, and HCV compared to the general population. The higher risk subgroup includes anyone who has used non-medical intravenous, subcutaneous, or intramuscular drugs in the last 12 months. If prior behaviors are unknown, by default a donor is considered at higher risk. As NAT testing detects infections that would go unnoticed in standard screening procedures, and because guidelines limit enhanced screening to higher risk donors, the rate of NAT false positives is constrained. Existing policy, then, helps mitigate the risk that organ recipients will acquire the illnesses that increasingly affect organ donors, and yet still minimizes the number false-positive tests.
However, even NAT screening will not prevent some infections from going undetected, and so the potential remains that false-negative tests will result in donor-derived infections. One multi-center study found that among high-risk donors with undetectable viral titers, the prevalence of HIV was 1 in 11,000 and HCV was 1 in 1,000 (among normal-risk donors, the prevalence was 1 in 50,000 and 1 in 5,000 respectively). This is not without consequences—between 2008 and 2011, 104 individuals developed donor-derived infections. The Organ Procurement Transplantation Network (OPTN), recognizes the possibility of transmission, and so it is standard practice to obtain informed consent prior to transplantation of an organ from a high-risk donor.
One can, though, doubt the quality of recipient consent when offering a life-saving organ. To be sure, recipients can give true consent for high-risk organs such as the kidney. Priority for kidney allocation considers time spent on the transplant list; patients have the liberty to make an autonomous decision as the consequences of declining a high-risk kidney are intolerable. However, organs like the liver are allocated on a ‘sickest first’ basis and do not consider time spent on transplant list. These patients do not have equal liberty to turn down a higher risk organ since doing so might result in the individual’s death before an average risk liver becomes available. Commentators have also pointed out that accepting higher risk organs is less likely to be autonomous since it is frequently a rushed decision, and might not truly reflect one’s preferences or values. Still, the impingement to informed consent and autonomy is preferable to the lost beneficence and justice from stopping transplantation altogether—the risk of infection is quite small (and non-zero even among average risk donors), and every day 22 people die waiting on the transplant list.
There is a related question about what to do when potential donors are known carry infectious disease. With increasing reliance on individuals who died from overdose as a share of total organ donors (currently 25% in Massachusetts), and given the high prevalence of transmissible disease among illicit drug users (Table 1), policies must balance preventing intended donor-derived infections against adequate supply of transplants available to the general population.
Transplanting organs from donors known to carry HIV became an option when the HIV Organ Policy Equity (HOPE) Act came into effect last year. For the 25 years before President Obama signed the act into law, organ transplantation from individuals known to carry HIV was prohibited, disqualifying some 500-600 would-be donors annually. The HOPE act initially allows for the transplantation of HIV-positive organs to HIV-positive recipients under experimental IRB protocols. Surgeons at Johns Hopkins performed the first such transplant in the U.S. earlier this year. After further research, and with certain safeguards in place, the HOPE act also opens the door for donation from HIV-positive donors to HIV-negative recipients.
In the short term, the ethical implications of the HOPE act is the promotion of donor autonomy, albeit currently for only a few donors. Interestingly, even though HIV-positive organs are initially limited to HIV-positive recipients, the HOPE act will also decrease the number of people on waiting lists, which confers beneficence to HIV-negative candidates as well.
In the long term, the ethics of knowingly infecting a person with HIV to save his or her life is a little murkier. On one hand, for liver patients, the coercive nature of the decision undermines consent to a lifetime of anti-retroviral therapy. On the other hand, when patients lack an alternative, living with HIV may likely be preferable to dying. If considered long before an organ is offered, potential recipients are more likely to adequately judge the pros and cons of acquiring a particular donor-derived infection. Furthermore, because treatments for HIV and HCV have differing side effects and patient costs, early in the transplant process recipients should consent to—or refuse—specific donor-derived infections as well. A policy of requiring consent specific to the disease would help improve the prospects of meaningful informed consent to a donor-derived infection.