Hepatitis B Virus Immunization Before and After Pediatric Liver Transplantation: Check, Catch-Up, and Check Again!

Abstract

To the Editor: We read with great interest the cross-sectional study by Leung et al 1 who evaluated hepatitis B virus (HBV) seroprotection in pediatric liver transplant (LT) recipients who were immunized before transplantation. The study shows that 67% of children immunized before LT had antibody titers below the protective threshold after LT. Time since LT was predictive of unprotective antibody titers by univariate and multivariate analyses, whereas age was predictive only by univariate analysis. Two questions emerge from reading the paper. First, is there a practical reason why the authors did not follow current recommendations to measure postimmunization titers to decide whether a booster dose was needed before LT 2? Second, did post-LT nonimmune subjects receive booster doses, and if so, did they reach protective titers? Applying recommendations would have been beneficial for these patients. It has been clearly demonstrated that protection against vaccine-preventable diseases is suboptimal in LT recipients 3, and that serology-based management is efficient to increase protection 4. Based on these studies, we recommended that all pediatric LT candidates in Switzerland have antibody titers measured pretransplantation, irrespective of their immunization schedule 3. Catch-up immunization was immediately recommended when unprotective titers were detected followed by repeat serologies 4–6 weeks later. Booster doses were administered as needed. Titers were checked one year after transplantation, and booster doses administered when required. To assess the efficacy of our intervention, we compared immunization status and serology in children who had LT before (P1 cohort) and after (P2 cohort) implementation of these recommendations 4. At the pretransplantation assessment, 6/44 patients (14%) had received ≥1 dose of HBV vaccine in P1, compared to 19/30 (63%) in P2 (p<0.001). After catch-up immunization, 23/27 (85%) P2 patients had protective titers. One year after LT, antibody titers were protective in 14/44 (32%) in P1, compared to 11/28 (39%) in P2 (p = NS). As expected, post-LT titers in P2 were lower than pre-LT (p < 0.001) and unrelated to age. Pretransplantation titers were correlated to titers 1 year after LT (p = 0.006). Seventy-seven percent of patients with booster immunization one year after LT reached protective titers. HBV antibody waning after transplantation is well reported 5, and could explain why time since transplantation was a risk factor for low antibody titers in the Houston cohort 1. However, Leung's study design does not allow distinguishing between antibody waning or primary immunization failure. Monitoring postimmunization antibody titers allows differentiating one from the other. Further, and given that pretransplantation titers are predictive of posttransplantation titers, such follow-up affords the opportunity for catch-up immunization before LT. Likewise, it is important to keep in mind that it is never too late to immunize before LT, as accelerated schedules have shown to be as protective as classic schedules 1. Finally, monitoring (6–12 months) of posttransplant titers once immunosuppression can be lowered increases the chances of timely, optimal protection posttransplant 2. In summary, although post-LT decline in HBV protection may not be avoidable, regular serology monitoring both pre- and post–pediatric LT and timely boosters ensure optimal protection after LT. A. G. L'Huillier1,*, V. A. McLin2 and K. M. Posfay-Barbe1 1Pediatric Infectious Diseases Unit, Department of Pediatrics, University Hospitals of Geneva & Geneva Medical School, Geneva, Switzerland 2Pediatric Gastroenterology Unit, Department of Pediatrics, University Hospitals of Geneva & Geneva Medical School, Geneva, Switzerland *Corresponding author: Arnaud G. L'Huillier, Arnaud.Lhuillier@hcuge.ch The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.