Use of HCV-infected Organs in Solid Organ Transplantation

An Ethical Challenge But Plausible Option

Gayatri Nangia; Kelly Borges; K. Rajender Reddy

Disclosures

J Viral Hepat. 2019;26(12):1362-1371. 

In This Article

Ethical Considerations

Though the opioid overdose crisis appears to have a silver lining in the form of organs available for transplantation, the urgency and context of their utilization remain disputed.[6,49] Some in the transplant community encourage widespread implementation of HCV-infected organ transplantation beyond the confines of clinical trials in order to maximize the benefit (ie transplant more patients) while these organs are at hand.[6,50–52] As such, the evidential burden appears to rest on those who oppose this standard-of-care approach to prove that the potential risks posed by HCV-infected organs warrant further investigation prior to their widespread use. Acknowledging the limitations of the existing data collectively, these cautious opponents insist that carefully monitored multi-centre studies involving extensive post-transplant follow-up evaluations are necessary in order to validate safety, develop policy framework and establish recipient selection criteria prior to endorsing HCV-infected organ transplantation as standard-of-care.[1,15,23,27,35,53–57] The regulatory oversight and controlled context of clinical trials offer the safest setting in which to utilize infected organs in uninfected recipients; continued study will enable investigators to fill existing gaps in the evidence supporting the safety of this practice, and thus ameliorate informed consent discussions. This ethically conservative approach takes myriad stakeholders' perspectives into consideration along a spectrum ranging from the individual (ie the organ recipient) to the societal level (eg all other listed candidates, families of donors and recipients, insurers and payers, policy makers). Ethical principles widely acknowledged in the field of medicine offer guidance for examining the moral considerations that must be taken into account prior to endorsing the widespread implementation of this strategy (Figure 1).[58]

Figure 1.

A depiction of salient ethical considerations, relevant to the individual transplant recipient and beyond, to consider before encouraging widespread implementation of this practice. DAA, direct-acting antiviral; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; OPO, organ procurement organization

By virtue of its practice, transplanting infected organs into uninfected recipients challenges the basic tenet of the Hippocratic Oath: do no harm. The notion of harm associated with this practice becomes increasingly perspectival when compared to the relative risk of mortality among hopeful transplant candidates on lengthy waiting lists. Some in the transplant community assert that the risks of missing the opportunity to receive a liver, heart or lung transplant outweigh the risk of HCV transmission.[51] Regardless of how marginal this risk may be, the data available thus far do not exclude the potential for an HCV-infected organ recipient to experience complications of post-transplantation HCV infection, especially without access to DAA therapy.[35,59] The existing practices for treating donor-derived infections (eg CMV, HBV, HIV) serve as a noteworthy paradigm for treating donor-derived HCV infection. Therapeutic advances have made HIV and HBV manageable, and HCV curable.[50–52,59,60] However, there presently exist difficulties in acquiring insurance approval for DAA therapy, even for patients with chronic HCV infection. One suggestion is for the Centers for Medicare and Medicaid Services to establish a process for obtaining a commitment for coverage of DAA therapy concomitantly with the commitment for coverage of transplantation and immunosuppression.[35] Further, these treatments remain expensive and so advocacy for the affordability of DAA regimens is imperative.[35] Even if DAA therapy can be secured at any cost, the risk of viral resistance/relapse/non-response to treatment and subsequent risks associated with liver disease progression remain relevant for prospective recipients to consider. It is crucial that these risks are discussed alongside the risks of refusing to be listed for an HCV-infected organ (eg disease progression and associated morbidity and mortality on the waiting list). One way to facilitate the comprehensive disclosure of risks and benefits of HCV-infected organ transplantation is through offering patient education sessions on which the foundation of the informed consent discussion is formed.[43,53] A team-based approach, inclusive of patients' hepatologists, surgeons and primary care providers, along with nurses, coordinators, pharmacists and independent advocates may aid in the dissemination and comprehension of risk information. Prospective recipients must also be reminded throughout the informed consent process that the decision to be listed for an HCV-infected organ remains entirely voluntary.

Beyond the level of the individual recipients of HCV-infected organs, the implementation of this practice would subsequently decrease organ waiting time, and therefore benefit the transplant candidates remaining on waiting lists. Additionally, transplantation of HCV-infected kidneys has demonstrated cost-effectiveness for both infected and uninfected recipients, due to decreased time on dialysis.[32,61] Receptivity of the general public, including patients listed for transplantation and their families, may vary by demography, as exemplified by observations noted in the THINKER trial.[62] While skepticism remains valid in the absence of evidence validating the long-term safety and effectiveness of this practice, the stigma associated with acquiring HCV infection must be addressed through ongoing education efforts. The availability of HCV-infected organs viable for transplantation may vary by region in accordance with overdose deaths; to ensure a just practice, these organs must be offered to all eligible transplant candidates. This underscores the importance of establishing standards for recipient selection to define eligibility (eg hepatic evaluation prior to listing).[15]

In summary, though the existing evidence collectively generates optimism, its limitations undermine the safety and benefit of this practice. The ethical permissibility of widespread implementation of this strategy hinges on whether (a) DAA therapy can be secured in advance, and (b) prospective recipients provide thoroughly informed consent, accepting the risks associated with HCV-infected grafts (particularly the risk of acquiring an HCV infection resistant to DAA therapy) in exchange for the benefits associated with being transplanted sooner. Dedicated interdisciplinary efforts must be made across all organ procurement regions to reform policies governing insurance formulary restrictions in order to ensure access to affordable DAA regimens for all listed transplantation candidates willing and able to accept HCV-infected organs.

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