Editorial on “Maximize Donor Cornea Use in a Hepatitis B Endemic Area via Serology Matching” : Transplantation

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Editorial on “Maximize Donor Cornea Use in a Hepatitis B Endemic Area via Serology Matching”

Hume, Simon J. MBBS, FRACP1,2; Thompson, Alexander J. MBBS, FRACP, PhD1,2; Holmes, Jacinta A. MBBS, FRACP, PhD1,2

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Transplantation 107(6):p 1242-1243, June 2023. | DOI: 10.1097/TP.0000000000004461
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Because of the scarcity of corneal grafts, optimization of donor cornea availability is paramount.1,2 However, the majority of eye banks restrict the use of corneas from donors with any history of hepatitis B virus (HBV) infection, which significantly limits the pool of corneas available for transplantation. This is especially relevant in HBV endemic regions where cornea graft demand exceeds donor pools. This has led to an expansion of donor eligibility criteria in some regions to allow utilization of donor grafts from individuals who have current or past HBV infection into consenting recipients. Taiwan is one such country, where corneas from donors with chronic HBV infection can be distributed to recipients who also have chronic HBV or demonstrate HBV immunity (HBV surface antibody [anti-HBs] >10 IU/mL). Although all donors are also screened for HBV core antibody (anti-HBc), there are no specific recommendations for the allocation of these corneas, which are currently distributed to all recipients irrespective of their HBV serostatus; therefore, a non-HBV immune recipient could receive a corneal graft from an anti-HBc–positive donor. There are limited data regarding the safety of these approaches, in particular regarding HBV transmission risk to recipients.3-7

In this issue of Transplantation, Chu et al8 bring new data to further address this. In this lookback study, they evaluated for risk of HBV transmission in recipients associated with corneal allocation practices in Taiwan. Discarded donor corneoscleral rims were cryopreserved immediately after transplantation and subsequently analyzed for HBV DNA by polymerase chain reaction according to donor HBV serostatus (HBV surface antigen [HBsAg]-positive, HBsAg-positive/anti-HBc–positive or HBV seronegative [HBsAg-negative/anti-HBc–negative]). Recipients were recalled post–corneal transplantation to assess recipient HBV serostatus, serum HBV DNA, and liver function test profile according to donor corneoscleral HBV DNA graft status. HBV DNA was detected in corneoscleral tissue in 80% of HBsAg-positive donors and 9% of HBsAg-negative/anti-HBc–positive donors. HBV DNA was not detected in corneal tissue from HBV seronegative donors. Serum HBV DNA levels positively correlated with corneoscleral HBV DNA copy number. Donor anti-HBc serostatus had the highest sensitivity (1.00) and negative predictive value (1.00) for predicting corneoscleral HBV DNA, performing better than HBsAg or serum HBV DNA. Twenty-eight recipients of HBV DNA–positive corneas (70%) were able to be recalled, with a median follow-up time of 27.5 mo (range, 6.6–55.5 mo). Seven had chronic HBV infection at time of corneal transplantation; none developed HBV hepatitis (defined as raised transaminases or bilirubin) post–corneal transplantation. A further 19 recipients were HBV immune (HBsAg-negative/anti-HBs–positive, anti-HBs titer >10 IU/mL); 16 were also anti-HBc–positive. None developed HBsAg-seroreversion, HBV hepatitis, or HBV DNA–positivity during follow-up. There were only 2 HBV nonimmune recipients (HBsAg-negative/anti-HBc–negative/anti-HBs–negative) who received HBV DNA–positive grafts: one unintentionally received a corneoscleral HBV DNA–positive graft from an HBsAg-negative/anti-HBc–negative donor (serum HBV DNA not reported in this donor), and the second recipient was HBV seronegative at the time of transplantation (HBV serology/HBV DNA of the donor not reported), however, had protective anti-HBs titers 12 y before and received a booster HBV vaccine before transplantation with detectable anti-HBs after this. Neither patient seroreverted to become HBsAg-positive or developed HBV hepatitis or HBV DNA–positivity during follow-up. There were no data presented regarding outcomes after transplantation of corneas from donors with isolated anti-HBc–positivity without detectable corneoscleral HBV DNA.

The authors concluded that (1) HBV DNA can be detected in discarded corneoscleral rim tissue of some donors who are HBsAg-positive, as well as HBsAg-negative/anti-HBc–positive, even when serum HBV DNA levels were undetectable; (2) donor anti-HBc status can be used to triage risk of corneal graft HBV DNA–positivity with a negative predictive value of 100%; and (3) transplantation of HBV DNA–positive corneas from donors who are HBsAg-positive or HBsAg-negative/anti-HBc–positive into recipients who have current HBV infection or are HBV immune (anti-HBs–positive, titer >10 IU/mL) is safe, supporting current practices in Taiwan. The authors recommended that (1) donor anti-HBc testing become routine because of the risk of detectable HBV DNA in grafts from isolated anti-HBc–positive donors; (2) that recipient HBV serostatus should also be included in corneal allocation guidelines to appropriately allocate corneas to HBV-immune recipients when using corneas from HBV-exposed donors.

This study raises a number of interesting questions. What is the clinical significance of detectable HBV DNA in discarded corneoscleral rims, and can this cause HBV infection in recipients? What practical role is there for ongoing corneoscleral rim HBV DNA testing? Should expansion of corneal donation to include HBV-exposed donors be adopted in other HBV endemic regions and potentially more widely? Will vaccine-induced HBV immunity be sufficient to allow donation of HBsAg-positive grafts to individuals with isolated anti-HBs (>10 IU/mL)? To answer these questions, it is important to recognize some of the limitations of this study, and further data are required.

First, it is unclear what is the true clinical significance of detectable HBV DNA in discarded corneoscleral rims, particularly because they contain vascular tissue that are not present in the transplanted avascular corneal grafts. Real-time HBV DNA testing of corneoscleral rims is not feasible, and the lack of requirement for systemic immunosuppression posttransplant may further reduce the clinical significance of corneoscleral HBV DNA–positivity. The risk of HBV transmission from HBV DNA–positive corneas is an important question because it has additional implications regarding the further expansion of cornea donation pools beyond current recommendations. Future studies evaluating this would be helpful to further clarify onward risk of HBV transmission, and studies evaluating other potential scenarios, such as isolated anti-HBc–positive/serum HBV DNA–negative donor corneas into HBV nonimmune recipients and HBsAg-positive corneas into HBV vaccine–induced immune recipients, with either expectant management or with prophylactic antiviral therapy would be of interest. Furthermore, current corneal allocation guidelines are inconsistent in the allocation of HBsAg-positive/anti-HBc–positive grafts and HBV serostatus testing of donors and recipients, and this should be addressed and clarified. Preemptive HBV vaccination in nonimmune recipients may further expand available corneal pools, and this should be evaluated, particularly in HBV endemic regions where there is a shortage of available corneal graft supply; preliminary data from this study suggest that this approach is safe.

Second, this was a small study with only 28 recipients of HBV DNA–positive corneas enrolled in the lookback study, with 30% lost to follow-up or declining participation, and the lookback study design reported only a single time point of HBV outcomes (median follow-up 27.5 mo, but as short at 6.6 mo). Therefore, important HBV-related outcomes may have been missed, and larger prospective studies with longer-term and protocolized longitudinal follow-up are required. Therefore, although some limitations exist, we believe that Chu et al provided compelling data to support the expansion of corneal donation to include donors exposed to HBV infection in appropriately selected recipients in HBV endemic regions and potentially beyond highlights the need for mandatory inclusion of anti-HBc in HBV donor and complete HBV serostatus recipient screening strategies into guidelines to enhance safety of this approach, highlights an opportunity for proactive and preemptive HBV vaccination of recipients as a strategy that may further expand corneal donation pools, and highlights the need for further information regarding the true risk of HBV transmission from transplantation of HBV-exposed corneas.


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