Systematic Review

Hepatitis C Viraemic Allografts to Hepatitis C-negative Recipients in Solid Organ Transplantation

Taaj Raasikh; Taher Jamali; Avegail Flores; Ronald T. Cotton; Venkat Ramanathan; Henkie P. Tan; Ruben Hernaez

Disclosures

Aliment Pharmacol Ther. 2021;54(5):571-582. 

In This Article

Discussion

Our study on 852 recipients of SOTs from HCV viraemic donors has three major findings. First, the success rate of achieving SVR12 with DAAs is apparent across the solid organs analysed: 100% of all the patients who were eligible for SVR12 had achieved an undetectable viral load with minimal side effects reported from DAAs. First-line DAA therapies can be initiated without the requirement for genotype identification and are considered pangenotypic (Table 1 and Table 2).

Second, the rate of graft failure and patient death was low compared to the survival benefit. No deaths reported in the studies were deemed to be related to HCV complications. Additionally, there were only four studies[17,19] that reported a possible change in immunosuppression levels due to concurrent use of DAAs (Tables S6–S8). Furthermore, across the studies, only seven patients had a relapse in viral load and had to undergo another course of DAAs.

Third, the cumulative data of insurance coverage of DAA treatment from all studies that reported these data indicated that in most studies, treatment cost was covered by patients/patient insurance, with only a minority reporting coverage by the hospital or assistance grants.

While transplant outcomes in this unique population are promising, there are some potential noteworthy complications. Four patients developed fibrosing cholestatic hepatitis, one patient developed intrahepatic biliary sclerosis, two patients developed the compartmental syndrome, one patient developed focal sclerosing glomerulonephritis and one patient developed proteinuria. Interestingly, these complications were only reported in studies with a reactive approach to DAA treatment compared to none in the prophylactive/pre-emptive approach. Thus, when discussing the informed consent, these potential complications should be stated (Figure 2).

Figure 2.

Proposed ideal workflow for HCV Viraemic solid organs to HCV-negative recipients

Based on our results, we think that expanding donor availability using solid organs from HCV viraemic donors should be considered a standard of medical care.[48] Therefore, it is arguable whether IRB approval is needed or not as this could be a potential cause for delay in treatment. We think that the recommendation from the American Association for the Study of Liver Disease (AASLD) and the Infectious Diseases Society of America (IDSA) societies (last updated on August 27, 2020) is outdated. Their recommendation "due to the limited and heterogeneous experience and lack of longer-term safety data, strong consideration should be given to performing these transplantations under IRB-approved protocols" was based on the 2017 American Society of Transplantation Consensus Conference on Hepatitis C Donors,[10] with papers more than 5 years old to date. Our data provide evidence to support this donation practice.

In agreement with AASLD/IDSA, we recommend that informed consent specifically details potential risks and benefits of an HCV-negative recipient accepting a solid organ from an HCV viraemic donor. Consent should include a detailed discussion about the likelihood of HCV transmission, the subsequent need for treatment with DAAs and the side effects of both HCV and DAA therapy and some of the potential medical complications noted in this review. Transplant centres that perform these transplants should have a strategy to ensure that the patient has the means to obtain treatment for HCV and maintain both close and long-term follow-up. Recommendations from AASLD/IDSA are to start pre-emptive DAA treatment, ideally within the first 7 days, and to do so even if the HCV viral load is pending.[49] This approach is clearly preferred, as complications were seen in the reactive approach. However, access to DAA therapy is a major factor when determining which approach is available for patients.

Insurance coverage is probably the main hurdle for successful HCV viraemic donation. The studies were not consistent on payor report. Still, in those studies that addressed insurance, some relied on third-party payers, which sometimes led to reported delays in the initiation of DAAs. In Morris et al, one patient's DAA initiation was delayed by 169 days due to insurance appeals.[25] Aslam et al mentioned delays averaging 30 days.[22] Despite these delays, there was no reported major impact on clinical and graft outcomes or SVR. Other centres such as those described in Cypel et al and Woolley et al were able to obtain grants or have the hospital cover the costs in some cases (Table S3).[27,31]

Our work is limited by the lack of standardized reporting and varying definitions of abstracted studies. Some studies reported follow-up time intervals as medians and some as means. There was also heterogeneity in definitions, including graft failure and graft rejection, so these variables could not be uniformly analysed in a meta-analysis. There was significant variability in reporting other administrative and financial variables, including the time to insurance approval for DAA treatment, IRB approval and cost coverage for DAA treatment if not approved by insurance. Additionally, 115 of the 852 SOTs (13.5%) or 38 kidney, 41 heart, 28 liver and 8 lung recipients had incomplete SVR12 data at the time of publication for various reasons as detailed in Table 1 and Table 2 and Table S2. Also, the authors did not report if hospital admissions were required due to the side effects of DAA. However, based upon the side effects in non-transplant patients receiving DAA, the rate is expected to be very low.

Future studies should include a minimum of 1-year follow-up, precise reporting on graft failure and rejection using standard definitions and documentation of SVR12 in all participants. Additionally, transplant centres should have a protocol on pre-transplant NAT check and post-transplant NAT check at 1, 4, 8 and 12 weeks from initiation of DAA.[50] We provide a proposed workflow for solid organ HCV NAT-positive donors to HCV-negative recipients, including consent highlights, proposed team members of the transplant team and a proposed excerpt for IRB in Figure 2. Additionally, future studies should focus on more specific treatment parameters and barriers to obtaining treatment, for example, studies comparing head-to-head outcomes between reactive and prophylactic/pre-emptive approaches to DAA therapy and determining the optimal duration of treatment for prophylactic/pre-emptive approaches. There should also be a joint effort to tackle the most complex financial barriers to transplantation of organs from HCV viraemic allografts, including the high cost of DAA treatment, the time to insurance approval for treatment and, finally, the impact of these increased costs on transplant outcomes.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....