This study further consolidates the emerging evidence that anti-HCV NAT negative and positive organs can be transplanted into negative recipients effectively and safely. While thousands of organ transplants are performed annually, many patients remain on the waitlist and a substantial amount will die waiting [16, 17]. This has generated significant demand for novel strategies to broaden the donor pool. The catastrophic opioid crisis has led to a substantial increase in anti-HCV NAT negative and positive organs that can be transplanted into negative recipients. Our study provides a real world Canadian multiorgan transplant experience that shows that this can be successfully done outside of a research study.
There were 11 patients that received anti-HCV NAT negative organs in this study and none of these patients developed a donor derived HCV infection after 3 months of follow up post-transplant. The risk of a donor derived HCV infection in the setting of an IRD is variable depending on the risk category of the donor. The risk of HCV infection during the window period usually ranges from 1.4 to 40.8 per 10,000 donors by ELISA and NAT [13]. All 22 patients that were transplanted with an anti-HCV NAT positive organ developed viremia and this is consistent with prior studies where essentially all recipients transplanted with anti-HCV NAT positive organ developed a donor derived HCV infection [18,19,20,21,22]. This study demonstrated some of the benefits of transplanting anti-HCV NAT positive organs into negative recipients. It expanded the donor pool at our centre, led to shortened wait times for organ transplantation, and the transplantation of organs with better predicted graft survival as manifested by lower KDPI and DRI.
We did not encounter any significant difficulties in obtaining insurance coverage for all patients in our cohort. While there were some minor delays in obtaining approval for coverage, the median time to treatment start was 42 days. We did not see any cases of fibrosing cholestatic hepatitis in our patient cohort even in cases where treatment may have been delayed. However, the pre-transplant patient with NAFLD receiving a kidney transplant that was treated and cured for HCV with persistent hepatocellular elevation was found to have NASH with moderate fibrosis on liver biopsy due to NASH. We did not see any graft failure due to HCV in any of the patients with donor derived HCV infections. One comorbid patient had a prolonged intensive care course with enteral feeds that limited treatment initiation. They were eventually started on treatment, but would die due to invasive fungal infection. This highlights the need for pre-transplant careful selection of the candidates for this novel approach.
All patients that developed a donor derived HCV infection from an anti-HCV NAT positive organ were treated with DAAs. The most commonly used DAAs were the pangenotypic agents sofosbuvir/velpatasivir and glecaprevir/pibrentasvir. Therapy was based on several factors including insurance coverage, genotype, and creatinine clearance at time of treatment. The SVR12 rate was 100% in all patients that were treated with DAAs that completed treatment and this is consistent with prior studies. There were no significant adverse events related to treatment. We did not encounter any significant alterations to the immunosuppression regimens while on treatment or any drug-drug interactions requiring medication adjustment. There were no differences in achieving HCV eradication in those that received or did not receive a T cell depleting agent. While the cost of treatment for DAAs can be expensive, transplanting patients using anti-HCV NAT positive organs has already been shown to be cost effective [23].
The organs transplantations in this study were diverse and included kidneys, livers, SLK, kidney pancreas and a heart. In addition to this we transplanted 2 recipients that had undergone treatment and cure for HCV pre-transplant with livers from NAT positive organs and we were successful in curing them again after reinfecting them with HCV. None of the patients in this study developed any HBV or HIV infection. We did not encounter any reactivation of HBV in HBcAb patients that were treated for HCV. HBV prophylaxis was utilized where appropriate specifically in liver transplants as per our institution protocol.
The treatment of donor derived HCV infection in the post-transplant setting can be accomplished by either a delayed or prophylactic approach. Viremia is clearly demonstrated in the delayed approach with treatment started thereafter whereas patients are empirically treated before viremia is manifested in the prophylactic approach. In this study we used a delayed approach as insurance providers required determination of viremia before approving therapy. There are merits to a prophylactic approach as treatment duration can be shorter and starting treatment immediately may limit the risk of fibrosing cholestatic hepatitis. However, complex patients might not be able to undergo treatment immediately after transplant [24,25,26,27,28,29,30]. Insurance providers will need to approve treatment pre-transplant for this approach to be more practically utilized outside of a research study. It is imperative to commit to treatment once viremia occurs.
Limitations of this study include the small sample size, being a single centre experience, the potential for bias, and the lack of long-term follow up.