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

Renal Transplantation With HCV-positive Organs

For those with end-stage renal disease, kidney transplantation is considered the treatment of choice, offering a better life expectancy and quality of life than dialysis. However, the number of transplant candidates on the waitlist in the Unites States has increased substantially and wait times in some parts of the country exceed 5 years. This has resulted in as high as 9.4 waitlist mortality per 100 patient years in certain transplant regions.[5,20] The number of anti–HCV-positive kidneys that has been transplanted into anti–HCV-positive recipients has increased to 335 per year, yet more than 500 transplantable kidneys from HCV-infected donors are still discarded every year.[21–24] In fact, kidneys from HCV-positive donors are 5× more likely to be discarded than used.[25] Even in the era of DAAs, an HCV-positive kidney is 2.4× more likely to have been recovered but not transplanted than a non-infected kidney.[26]

Many providers are hesitant about transplanting HCV-positive organs because of the potential post-transplant complications of HCV which include hepatic issues such as cirrhosis and FCH as well as the extra-hepatic concerns like glomerulonephritis, which can cause graft dysfunction.[27] In 2017, data from the national transplant registry showed that, while HCV-positive kidneys were not associated with an increased risk of acute rejection, transplantation with an HCV-positive kidney was associated with an increased risk of death and allograft loss.[28] In contrast, observational data prior to the advent of DAAs (1990–2007, n = 468) noted good long-term outcomes when HCV-positive recipients were transplanted with HCV-positive kidneys.[29] These data had a mean follow-up of 74.5 months and showed that HCV-positive donor status was not a significant predictor of patient survival, graft survival and significant liver disease development. However, since NAT testing was not yet implemented, the presence of viremia in the donor organs was unknown.[29] In the era of DAA-based treatments for HCV, the safety of transplanting HCV viremic kidneys into HCV-uninfected patients has been a topic of further research (Table 2). In 2017, an open-label, single-group, pilot trial (THINKER) looked specifically at the safety and efficacy of transplanting HCV genotype-1 viremic kidneys into HCV-negative recipients.[23] All 10 recipients tested positive for HCV RNA on day 3 post-transplantation and were subsequently treated with elbasvir/grazoprevir (EBR/GZR), a combination of an NS5A inhibitor and a NS3/4A protease inhibitor. Given the restrictive efficacy of EBR/GZR, all donors were tested for HCV genotype with a rapid genotype testing platform and only genotype 1 organs were transplanted.[23] With this strategy, all patients achieved sustained virologic response 12 weeks after the end of treatment (SVR12) and showed good allograft function.[23] These patients also showed successful outcomes in longer-term follow-up.[30] In a continuation of the THINKER trial, the outcomes of 20 HCV-uninfected patients, who received HCV-viremic organs, were evaluated. Half of the patients' outcomes were analysed after 6 months and the other half after 12 months.[30] The patients who were evaluated at 12 months were the same ones in the preliminary THINKER trial, while the patients evaluated at 6 months were newly enrolled. All of these patients remained HCV RNA negative and, at follow-up, were found to have a self-reported good physical quality of life and excellent renal function.[30] In 2018, another open-label, single centre trial (EXPANDER) examined the safety and efficacy of transplanting HCV genotype 1, 2 and 3 viremic kidneys into HCV-uninfected recipients.[31] All 10 recipients were given a dose of EBR/GZR immediately before transplantation, while there was concurrent donor genotype testing done. Within 7 days post-transplant, the donor genotype results became available and the recipients of HCV genotype 1 organs were treated with GZR/EBR alone, while genotypes 2 and 3 donor recipients were treated with EBR/GZR plus sofosbuvir (SOF), an NS5B inhibitor.[31] No patients had treatment-related adverse events and none had detectable HCV RNA 12 weeks after treatment.[31] Lastly, a more recent modelling analysis suggests this strategy has the additional benefit of being cost-effective because transplanting HCV-infected donor kidneys into HCV-infected recipients decreases patients' time on the waitlist and therefore also their time on haemodialysis.[32] While these preliminary data are promising, without large prospective studies, we cannot yet draw conclusions about adopting this strategy on a larger scale.

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