Using Organs from Hepatitis C–Infected Donors: A Cautionary Experience

Direct-acting antivirals (DAAs) have revolutionized the landscape of hepatitis C virus (HCV) treatment, offering cure rates of >95% with 8–12 wk of treatment. The World Health Organization is now advocating for HCV elimination by 2030, hence the increased treatment rates, especially in at-risk populations such as people who inject drugs.1 Before the availability of DAAs, hepatitis C viremic liver donors were considered unsuitable for transplantation because of the risk of fibrosing cholestatic hepatitis and graft loss. In the post-DAA era, several studies have demonstrated the feasibility of using HCV viremic donors as a viable option to expand the donor pool.2 Multiple groups have demonstrated successful achievement of sustained virologic response after transplanting HCV viremic grafts into HCV antibody negative recipients.3 Several leading groups including the American Society for Transplantation, the American Association for the Study of Liver Diseases and the American Journal of Kidney diseases have protocols in place regarding the use of these organs. In line with these current guidelines, hepatitis C viremic donors have now been considered transplantable in British Columbia. According to our local guidelines, all HCV viremic donors undergo genotyping and DAA resistance testing, although results are typically available 1–2 wk posttransplantation. Recently, a 25-y-old donor with hepatitis C (genotype 1A), reportedly antiviral treatment naïve, was assessed for organ donation (liver only). The organ was accepted but ultimately the liver was deemed unsuitable because of excessive steatosis. The intended recipient was hepatitis C negative. It was later reported that this potential donor had a pan resistant strain of the virus (Table 1), and that our available antivirals would not have been effective in curing this strain of hepatitis C. Although the donor had never received antiviral treatment, they had a history of active drug use and clearly acquired HCV from an antiviral resistant community source. TABLE 1. - Resistance testing for donor strain of hepatitis C HCV NS3 drugs Asunaprevir Resistance possible Glecaprevir Resistance possible Grazoprevir Resistance likely Paritaprevir Resistance likely Simeprevir Resistance likely Voxilaprevir Resistance possible HCV NS3 key resistance mutations identified: Q80K P334S HCV NS5A drugs Daclatasvir Resistance likely Elbasvir Resistance likely Ledipasvir Resistance likely Ombitasvir Resistance likely Pibrentasvir Resistance possible Velpatasvir Resistance possible HCV NS5A key resistance mutations identified: Q30R HCV NS5B drugs Dasabuvir Mutations detected: effect unknown Sofosbuvir Resistance possible HCV NS5B key resistance mutations identified: S62N N444D HCV, hepatitis C virus. We present this case as a word of caution for using organs from hepatitis C viremic donors. Once effective resistance testing is available in a timely manner, this may be a safe practice. With the current opioid crisis across North America, there is a risk that the circulating strain of HCV is becoming increasingly resistant even in treatment-naive individuals. The prevalence of resistance is currently unknown, although a recent meta-analysis suggests that among patients with virological failure following therapy (<5% of all patients treated), approximately 80% have resistance associated substitutions present.4 A recent report demonstrated that the presence of resistance associated substitutions increases after DAA exposure.5 We can infer that as more patients are treated and reinfected with hepatitis C, resistance can be expected to increase. If these organs are transplanted, patient outcomes could be dire because of untreatable hepatitis C infection. We suggest that the transplant centers consult their local center for disease control to identify local patterns of hepatitis C resistance before continuing to utilize viremic hepatitis C donors. We additionally suggest that where possible, donor history of prior exposure to or treatment for hepatitis C be obtained before transplantation.

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