The scarcity of kidneys for transplantation and high mortality among patients on the waiting list have led some patients to accept kidney transplants that carry elevated risks of transmitting infections or cancer. In certain cases, such as the transmission of cytomegalovirus, physicians can anticipate these events and institute preventive measures. But transplant teams often discard kidneys from donors with hepatitis C virus (HCV) infection because of the many complications and historical barriers to successful treatment of HCV. We believe, however, that new antiviral therapies with cure rates exceeding 95%1 should prompt transplant leaders to view HCV-positive organs as a valuable opportunity for transplant candidates with or without preexisting HCV infection.
Of course, intentional HCV infection through transplantation will require rigorous programs that address the complexity of HCV treatment options, bolster informed consent, and overcome cost concerns. But the resulting expansion of the donor pool could save hundreds of lives each year.
Kidney transplantation extends life and saves money as compared with long-term dialysis,2 but it’s available to an ever-smaller percentage of patients. In many regions of the United States, average waiting times for a kidney transplant exceed 5 years, especially for patients with blood type O or B, for whom there’s a large imbalance between organ supply and demand. Average mortality among wait-listed patients is 4% per year, and rates are much higher among diabetic and elderly transplant candidates. The kidney-transplant waiting list exceeds 100,000 candidates, and thousands of other patients receiving dialysis who might benefit from transplantation are never even referred. These grim realities have prompted aggressive efforts to procure kidneys that would previously have been considered unacceptable, including kidneys from donors older than 70 years of age, kidneys that have sustained acute injury, and kidneys with diverse infections.
Using national registry data, we identified 3273 HCV-antibody-positive deceased donors from 2005 through 2014 (the positive predictive value of the antibody test for chronic HCV infection is 80 to 90%) for whom organ donation was authorized. Of these 6546 kidneys, only 2402 (37%) were transplanted; 91% of the recipients had documented HCV infection. The other kidneys were discarded, although most were of good quality (according to the Kidney Donor Profile Index, a widely used transplant metric). These discarded kidneys could have benefited more than 4000 patients during that period and provided more than 12,000 years of graft life by 5 years after transplantation (see tableDisposition of 6546 Kidneys from 3273 Deceased Donors with Hepatitis C Antibody between 2005 and 2014.). In addition, an unknown number of kidneys were never procured because of legitimate concerns that no transplant center would accept them.
This reluctance to use HCV-positive organs reflects past experiences with post-transplantation HCV complications, both hepatic (e.g., cirrhosis) and extrahepatic (e.g., glomerulonephritis that can injure the transplant). It also stems from the problem that interferon, the historical mainstay of HCV treatment, causes transplant rejection. In the United States, the overwhelming majority of HCV infections are caused by genotype 1, which has historically been difficult to treat. For these reasons, HCV-positive kidneys are rarely transplanted into uninfected recipients, and the limited data available suggest that uninfected patients who do receive them have high mortality.3
Now, however, highly effective novel therapeutics may transform the way that transplant physicians and their patients think about HCV-positive donated kidneys. These therapies do not require interferon, and they cure HCV in more than 95% of patients. Acceptance of transplantation of HCV-positive kidneys would result in shorter waiting times. According to one study, the median waiting time was 469 days for patients who accepted HCV-positive kidneys, versus 856 days for patients who received HCV-negative organs; an unknown number of additional patients died before they could receive a transplant.4
Nevertheless, using HCV-positive transplants in uninfected patients raises many concerns. Which patients should be encouraged to accept these kidneys? HCV treatment is costly: more than $80,000 for a 3-month regimen. Can payment for post-transplantation HCV treatment in uninfected patients be guaranteed? Even if patients receive such treatment, what are the residual risks of viral complications? What is the risk of transmission to intimate personal contacts? It is difficult to estimate the size of these risks because newly infected transplant recipients will simultaneously receive immunosuppressive drugs.
These concerns may be allayed by recent experience with treatment of HCV in liver-transplant recipients. When an HCV-positive patient receives an HCV-negative liver, the allograft is immediately exposed to HCV from the recipient and becomes infected. Clinical studies have demonstrated that these patients have high HCV cure rates, suggesting that immunosuppression does not impede HCV eradication and that interactions between HCV and transplant drugs can be successfully managed.5 Nevertheless, given the uncertainties about risk, is informed consent possible?
The ethics of knowingly infecting transplant recipients with HCV depends on the rigor of informed consent and the willingness of medical professionals to give greater weight to patients’ autonomy than to minimizing the possibility of iatrogenic harm. In our view, transplant physicians should offer HCV-positive organs to uninfected patients who have a high risk of health deterioration if they continue dialysis (e.g., elderly patients or those with serious coexisting conditions such as cardiovascular disease), disadvantageous blood types, or other conditions that probably mean many years of waiting before an appropriate HCV-negative kidney can be obtained. For such vulnerable patients, HCV-positive donated kidneys could provide a singular opportunity to undergo transplantation. Given the survival benefit of kidney transplantation in patients with chronic HCV, there is reason to believe that providing HCV-positive kidneys and HCV therapy to HCV-negative recipients will lead to better outcomes than dialysis.
Informed-consent processes should include explicit communication of the uncertainty about the HCV cure rate with post-transplantation treatment and the potential risks of viral complications. Severe complications may include acute hepatitis or fibrosing cholestatic HCV, although those problems rarely develop in recipients of transplanted organs other than livers. Consent processes should start when the patient registers on the waiting list and be reinforced at later meetings. A two-stage consent process already exists for transplantation of organs designated as high-risk by the U.S. Public Health Service; this approach will only require modifications specific to the uncertainties regarding HCV after transplantation. In initial demonstration projects, transplant teams should seek oversight from institutional review boards. Subsequently, multicenter trials could collect comprehensive data on HCV cure rates, viral complications, and time to transplantation for patients who accept these organs.
Although transplant teams may feel challenged by the complexity of these discussions, there are precedents for them. Many physicians have experience with risk communication related to transplantation of organs from donors with past infections or cancers. In the 1990s, similar concerns were raised about organs that tested positive for hepatitis B core antibody — which are now commonly transplanted, thanks to reassuring results. Given the complexity of decision making in the realm of HCV-positive kidney transplantation for HCV-negative recipients, we believe that research should focus on relevant patient-centered outcomes. Studies could examine communication by physicians and the proportion of patients who regret accepting an HCV-positive kidney.
Cost concerns could derail such an initiative. But the Centers for Medicare and Medicare Services (CMS) and other payers could create mechanisms for hospitals to obtain pretransplantation agreements for post-transplantation HCV treatment. Copayments for treatment should be modest, opening this pathway to transplantation to patients with limited means. Though the costs of transplanting HCV-positive kidneys into uninfected recipients would be high, they might well be substantially offset by savings from reduced dialysis time for recipients who would otherwise wait longer for a kidney.2 Given the increased probability of complications, CMS and insurers could also authorize higher payment structures for centers that used higher-risk kidneys such as HCV-positive organs.
Novel antiviral therapies will gradually transform how we think about HCV. HCV-positive kidneys could become a valuable resource for patients who would otherwise have little chance of kidney transplantation. Taking advantage of this resource will require providers, regulatory authorities, and payers to reconsider notions of reasonable risk.
Originally posted by: nejm.org
Full references: P.P. Reese, P.L. Abt, E.A. Blumberg, and D.S. Goldberg | N Engl J Med 2015;373:303-305