During the last 2 decades, the growing disparity between organ availability and the number of candidates for organ transplantation has compelled the use of sub-optimal or marginal donors. Extensive donor test is recommended to prevent transmission of disease by transplantation. Traditionally, syphilis screening involves a nontreponemal anticardiolipin serological test (eg, Rapid Plasma Reagin [RPR] or Venereal Disease Research Laboratory [VDRL]). Subsequently positive results are confirmed by a specific treponemal test (eg, TPPA)12. Nowadays, it has the trend to use treponemal-specific EIA for syphilis screening and a nontreponemal test will be taken on positive results13,14. As we can see in Table 1, we would miss syphilis positivity if we tested our donors in the traditional way. However, the latter method also has its limitation with about 17% of EIA results false-positives and discordant test results as reported14. Hence, it is recommended that discordant results should be tested using the TPPA test15. So, we use EIA as the initial screening method, and positive results will be confirmed by TPPA and RPR.
The EIA test was negative in all recipients before transplantation. One recipient (case 13) had positive EIA and TPPA at day 5 but his TPPA results was negative and EIA remained positive afterwards. An explanation of this phenomenon may be the passive transmission of antibodies from donor at transplantation or transmission of lymphocytes with the grafts, which has been described already in kidney transplantation16,17. Case 10 had negative EIA at day 5 but had positive EIA and PRP (1:1) at month 1, it was considered that he was infected with syphilis in the past, but had been cured and was not infectious. Afterwards, his PRP became negative and EIA remained positive18. With this recipient (case 10), we should be aware of the possibility of syphilitic hepatitis. It is uncommon in immunocompetent individuals10 while it has been depicted in immunocompromised patients, such as those infected with human immunodeficiency virus (HIV)19. In syphilitic hepatitis, there would be a notable increase in alkaline phosphatase and a modest increase in aspartate aminotransferase, alanine transaminase and bilirubin along with clinical symptoms including rash and hepatomegaly10. Case 14 had weakly positive EIA and negative TPPA at month 1 which was considered false positive. After reexamination, his EIA became negative.
Though positive EIA and TPPA results with negative RPR do not mean active syphilis, it is recommended that recipients of potentially infected organs should be treated with an appropriate course of benzathine penicillin20. Fischer et al20 recommend 3-weekly doses 2.4 MU of intramuscular benzathine penicillin while UK guidelines21 recommend benzathine penicillin 2.4 MU as a single-dose intramuscular injection, or doxycycline 100 mg by mouth twice daily for 14 days, as alternative therapy. Gibel et al3 also recommend a single dose of 2.4 MU of benzathine penicillin. Ko et al22 and Marek al23 utilize 3-weekly doses 2.4 MU of intramuscular benzathine penicillin as the prophylactic therapy. Cortes et al9 consider two doses of intramuscular 2.4MU benzathine penicillin a week apart to be an appropriate regime for prophylaxis and treatment of early syphilis acquired via transplantation. In our case, we split the difference of the above. We recommend single dose 2.4 MU of intramuscular benzathine penicillin with or without another 2-weekly doses 2.4 MU of intramuscular benzathine penicillin according to the serology results of syphilis at day 5 after transplantation.
The follow-up duration of recipients with syphilis-positive liver grafts is unclear. There was no documents especially for this. Ko et al22 monitored their patients using Venereal Disease Research Laboratory (VDRL) and Treponema pallidum hemagglutination (TPHA) at 2, 4, 6, and 12 months after transplantation. Cortes et al9 monitored their patients at 1, 3, 6 and 12 months after transplant using TPPA, RPR and an immunoblot for IgM and IgG. Marek al23 monitored their patients similarly to Cortes et al9.
Summarily, our cohort study illustrates that syphilis-positive liver grafts did not result in poor prognosis or increase the morbidity and mortality of the recipients after liver transplantation. Benzathine penicillin is effective to protect recipients from transmission of syphilis. Furthermore, we summarize and share our experience in the management of recipients with syphilis-positive liver grafts. With the increasing disparity between donors and recipients, it is vital to be aware that syphilis-positive liver grafts are safe for recipients as long as prophylactic antibiotics are administered to the recipients.