Abstract

Varicella is one of the most common vaccine-preventable infections after paediatric solid organ transplantation; thus, vaccination offers simple and cheap protection. However, children with liver disease often progress to liver transplantation (LT) before they reach the recommended vaccination age. As a live vaccine, varicella zoster virus (VZV) vaccination after transplantation is controversial; however, many case series demonstrate that vaccination may be safe and effective in paediatric liver transplant recipients. Only limited data exists describing long-term vaccination response in such immunocompromised patients. We investigated retrospectively vaccination response in paediatric patients before and after transplantation and describe long-term immunity over ten years, including the influence of booster-vaccinations. In this retrospective, single-centre study, 458 LT recipients were analysed between September 2004 and June 2021. Of these, 53 were re-transplantations. Patients with no available vaccination records and with a history of post-transplant lymphoproliferative disease, after hematopoietic stem cell transplantation and clinical chickenpox were excluded from this analysis (n = 198). In total, data on 207 children with a median annual follow-up of 6.2 years was available: 95 patients (45.9%) were unvaccinated prior to LT. Compared to healthy children, the response to vaccination, measured by seroconversion, is weaker in children with liver disease: almost 70% after one vaccination and 93% after two vaccinations. One year after transplantation, the mean titres and the number of children with protective antibody levels (VZV IgG ≥ 50 IU/L) decreased from 77.5% to 41.3%. Neither diagnosis, gender, nor age were predictors of vaccination response. Booster-vaccination was recommended for children after seroreversion using annual titre measurements and led to a significant increase in mean titre and number of protected children. Response to vaccination shows no difference from monotherapy with a calcineurin inhibitor to intensified immunosuppression by adding prednisolone or mycophenolate mofetil. Children with liver disease show weaker seroconversion rates to VZV vaccination compared to healthy children. Therefore, VZV-naïve children should receive basic immunization with two vaccine doses as well as those vaccinated only once before transplantation. An average of 2–3 vaccine doses are required in order to achieve a long-term seroconversion and protective antibody levels in 95% of children.

Highlights

  • Paediatric liver transplantation is a well-established procedure in patients with chronic as well as acute liver failure

  • A total of 458 paediatric liver transplantations were performed during the analysis period from September 2004 to June 2021

  • More than 54% were vaccinated against varicella zoster virus (VZV) at least once before liver transplantation, with a median age of 1.04 years, and 74 of 207 patients (35.7%) received a complete primary series of two doses

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Summary

Introduction

Paediatric liver transplantation is a well-established procedure in patients with chronic as well as acute liver failure. An initial infection with varicella zoster virus (VZV) is often mild in immunocompetent children, with a fever and skin rash, but severe cases involving the central nervous system or pneumonia have been reported [5]. Case reports describe severe cases with visceral involvement (e.g., pneumonitis, hepatitis, or meningoencephalitis) and even death in immunocompromised patients [6]. Case series in liver-transplanted children mainly describe skin involvement where treatment with varicella-zoster immunoglobulin (VZIG) and/or acyclovir was begun [7,8]. Prolonged hospital stays with multiple organ failure [9] as well as cases of death related to VZV infection in liver transplant recipients have been reported [10]

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