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

Heart and Lung Transplantation With HCV-positive Organs

Between 2006 and 2017, the number of new active listings for heart transplants increased by 49% (from 2424 to 3623) and the number of candidates actively waiting for a heart transplant increased by 119% (from 1243 to 2727).[39] Thus, the rate of heart transplantation has not risen to match the increase in listings.[39] In spite of the increased demand for donor hearts, in 2016, over 600 hearts were discarded from deceased donors who either had active or previous HCV infection.[40] Based on the profiles of these donors, most of these discarded hearts, aside from being HCV-positive, were good quality organs.[40] Prior to the advent of DAAs, cardiac transplants from HCV-positive donors resulted in poor outcomes.[41] A 2004 analysis of 34 heart transplants from HCV-positive, viremia-unknown donors to HCV-uninfected recipients found that HCV-positive heart transplantation was associated with an increased mortality and with the development of accelerated de novo vasculopathy.[42] While these data indicate that transplantation of HCV-infected hearts may increase a recipient's risk for poor post-transplant outcomes, as treatment with DAAs has become standard of care, more centres are now willing to pursue a strategy of using HCV-infected organs. Between 2016 and 2017, the outcomes of heart transplantation with 10 HCV antibody positive/NAT-positive donors, two antibody positive/NAT-negative donors, and one antibody negative/NAT-positive donor were examined.[43] Of the 13 heart transplant recipients, 12 were HCV-naive patients, while one had a history of HCV, which was treated and cured before listing.[43] Nine (69%) patients acquired HCV post-transplant, all of whom had received anti–HCV-positive viremic donor hearts.[43] Eight of these nine patients were treated with DAAs, tolerated the therapy well, and achieved SVR12.[43] The ninth patient died before reaching the SVR12 time point due to a pulmonary embolism.[43] In 2017, the USHER trial looked at outcomes when HCV-infected organs were used in HCV-uninfected recipients of orthotopic heart transplants.[44] Ten patients waited a median of 39 days before receiving HCV NAT-positive, genotype 1 donor hearts.[44] NAT testing performed on day 3 post-transplant showed a detectable viral load in all 10 patients and they were then treated with EBR/GZR.[44] Nine of these 10 patients completed therapy and achieved SVR12.[44] The remaining patient did not complete therapy because of death 79 days post-transplantation from complications of antibody-mediated rejection.[44] However, this patient was HCV-NAT negative within 7 days of initiating therapy and remained negative.[44] In addition to this adverse event, two patients developed acute kidney injury and required dialysis, with one needing prolonged dialysis.[44] It was determined, however, that none of these adverse events were related to HCV or HCV treatment.[44] These preliminary data (Table 2), in the era of DAA-based therapy, have reopened the possibility of using HCV-infected donors for heart transplantation.

Similarly to heart transplantation, lung transplantation could also benefit from an increase in available organs through the use of HCV-infected donor lungs. However, when discussing heart and lung transplantation, it is important to note the additional challenge of post-transplantation ventilation. Heart and lung transplant patients are intubated for at least 24 hours post-transplant and complications requiring significantly longer periods of time on ventilation are also likely after transplantation. This presents a challenge for transplantation with HCV-infected organs because as of yet there are no approved intravenous or liquid formulation DAA therapies. In one recent clinical trial, investigators discussed alternative administration routes with the DAA manufacturer and delivered SOF/VEL to intubated patients nasogastrically, orogastrically and through percutaneous endoscopic gastrostomy.[45] However, this is not yet common practice and more trials are necessary to definitively determine whether this practice is safe and effective. On the other hand, if delay in HCV treatment is necessitated, the patient runs the risk of developing progressive liver disease, including the dreaded entity of fibrosing cholestatic hepatitis. Lung transplant patients also face the additional post-transplant challenge of receiving higher-intensity immunosuppression.

The need for donor lungs, like the need for donor hearts, continues to outpace the availability of donor organs.[46] Although there were 126 more donors in 2017, 1360 transplant candidates remained on the waitlist and 326 patients either died or were too sick for transplantation.[46] While there is clearly a need for more donor lungs, HCV-infected donor lungs have typically only been used for HCV-infected recipients and even this practice is not widespread. However, in the era of DAAs, more data are becoming available on the strategy of transplanting HCV-infected organs into uninfected recipients in order to determine whether the practice is safe and effective (Table 2). In 2017, five rapidly deteriorating, HCV-uninfected lung transplant candidates were transplanted with HCV-viremic donor lungs.[47] Three of the donor lungs had HCV genotype 1a, one had 1b and one had genotype 2.[47] The genotype 1-infected patients received sofosbuvir/ledipasvir (SOF/LDV), while the genotype 2-infected patient received sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks.[47] DAA therapy was initiated as soon as the recipients were determined to be clinically stable and able to initiate and complete their oral therapy without interruption.[47] This time ranged from 24 to 94 days post-transplant.[47] All five patients achieved SVR12 without HCV or DAA related adverse events and were alive upon follow-up to 9–12 months later.[47] In 2018, another analysis assessed the outcomes of transplanting HCV-viremic lungs into non-viremic recipients.[48] Nine patients were enrolled and waited a median time of 23 days from enrolment to transplantation.[48] All patients developed HCV viremia within the first week after transplantation and were treated with SOF/VEL for 12 weeks.[48] Four patients achieved SVR12 while the remaining patients had no detectable HCV RNA within 6 weeks of treatment. However, relapse was observed in two patients, with one displaying early fibrosing cholestatic hepatitis.[48]

Starting in 2017, a clinical trial (DONATE HCV) analysed outcomes of HCV-infected organ transplantation in 44 total patients, eight undergoing heart transplants and 36 undergoing lung transplants.[45] Recipients, who were uninfected pre-transplant, were given DAAs pre-emptively by administering SOF/VEL a few hours after transplantation for 4 weeks.[45] Since patients are intubated for at least 24 hours after heart or lung transplantation, at least the first and second doses of SOF/VEL were crushed, mixed with saline, and administered via nasogastric, orogastric or percutaneous endoscopic gastrostomy before extubation.[45] Thirty-five of the 44 patients enrolled had 6-month follow-up data available at publication.[45] All of these patients achieved SVR12 and had excellent allograft function.[45] Sixteen of these 35 patients also had 12-month follow-up data showing that 15/16 patients survived 1 year post-transplant.[45] The patient who expired was a heart transplant recipient who died 8 months after transplantation of a disseminated bacterial infection that was determined to be unrelated to the HCV infection.[45] In addition, the cohort of patients who received an HCV-infected donor long had more cases of acute cellular rejection requiring treatment compared to the cohort of HCV-uninfected lung recipients. However, after adjusting for confounding variables, this difference was determined to be insignificant.[45] Overall, no serious adverse events were considered to be related to the trial medication and all patients who reached the 6-month time point achieved SVR12.[45]

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