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Background: Although acute hepatitis caused by varicella zoster virus mostly develops in immunocompromised patients, hyperacute liver failure is very rare. To our knowledge, there are no previous reports on liver transplant patients. Methods: We report the first case of fatal hyperacute liver failure due to varicella zoster virus immediately after living‐donor liver transplantation without cutaneous lesions and review the literature. Result: The present case exhibited rapid development and progression of acute liver failure from postoperative days 11–13, despite being seropositive for varicella zoster virus but unvaccinated and on immunosuppression before transplantation. Especially in solid organ transplantation, only six cases of severe acute liver failure that included hepatic encephalopathy and/or impaired consciousness and sudden extremely high (> 4000 U/L) serum aspartate aminotransferase levels have been reported in heart, lung, and kidney transplant patients. Conclusions: Early diagnosis of hyperacute liver failure due to varicella zoster virus is challenging because the disease progresses rapidly and skin lesions are absent. [ABSTRACT FROM AUTHOR]

Background: Administration of live vaccines following liver transplant (LT) has historically not been recommended due to concerns regarding risk of vaccine‐attenuated disease. However, there is evidence suggesting that in select transplant recipients live vaccinations can be administered safely. Studies in other regions have indicated that despite this evidence many clinicians remain hesitant to administer live vaccinations. Method: A REDCap survey was distributed to gastroenterologists, pediatricians, and infectious diseases physicians at pediatric centers across Australia and New Zealand via email between September and November 2023. The survey included a series of questions regarding live vaccine and varicella postexposure prophylaxis (PEP) practices in pediatric LT recipients and barriers to live vaccine administration in this cohort. Results: There was a total of 16 responses to the survey, from 10 different pediatric centers, including 10/11 pediatric gastroenterology centers and all four pediatric LT centers in the region. Only 31% (5/16) of respondents (from 3/10 different centers) offer live vaccines. The main barrier to live vaccine administration was clinician reluctance and the main reason for not offering live vaccines was insufficient safety data. Sixty‐nine percent (11/16) of respondents take vaccination status and/or serology into account when deciding whether to offer varicella PEP to this cohort. Respondents universally offer varicella zoster immunoglobulin as PEP, though 31% (5/16) also offer antiviral medication. Conclusions: Many clinicians in our region remain hesitant to provide live vaccines to pediatric LT recipients, with concerns regarding insufficient safety data. Updated local guidelines may help to address this. [ABSTRACT FROM AUTHOR]

Background: Varicella‐zoster virus (VZV) pretransplant immunization rates, exposures, and posttransplant disease are poorly characterized among pediatric solid organ transplant (SOT) recipients in the two‐dose varicella vaccine era. Methods: A retrospective analysis of the electronic health records among children <18 years old who received SOT from January 1, 2011 through December 31, 2021, was performed at a single center to assess for missed pretransplant varicella vaccination opportunities, characterize VZV exposures, and describe posttransplant disease. Results: Among 525 children, 444 were ≥6 months old (m.o.) at SOT with a documented VZV vaccine status. Eighty‐five (19%) did not receive VZV Dose One; 30 out of 85 (35%) could have been immunized. Infants 6–11 m.o. accounted for 14 out of 30 (47%) missed opportunities. Among children ≥12 m.o. with documented Dose Two status (n = 383), 72 had missed vaccination opportunities; 57 out of 72 (79%) were children 1–4 years old. Most children had unclassifiable pre‐SOT serostatus as varicella serology was either not obtained/documented (n = 171) or the possibility of passive antibodies was not excluded (n = 137). Of those with classified serology (n = 188), 69 were seroimmune. Forty‐seven of 525 (9%) children had recorded VZV exposures; two developed varicella—neither had documented pre‐SOT seroimmunity nor had received post‐exposure prophylaxis. Nine additional children had medically attended disease: four primary varicella and five zoster. Of the 11 cases, 10 had cutaneous lesions without invasive disease; one had multi‐dermatomal zoster with transaminitis. Seven (64%) received treatment exclusively outpatient. Conclusions: VZV exposure and disease still occur. Optimizing immunization among eligible candidates and ensuring patients have a defined VZV serostatus pretransplantation remain goals of care. [ABSTRACT FROM AUTHOR]

Background: Vaccine preventable illnesses are important sources of morbidity, mortality, and increased healthcare costs in pediatric LT recipients. Our aim was to measure the seroprevalence of antibodies to measles and VZV in this population. Methods: We conducted a retrospective chart review of 44 patients who received LT before age 18 at UCLA Mattel Children's Hospital from January 2008 to December 2017. Results: Median age at transplantation was 2.5 years (IQR 1.2–7.7). Post‐transplant measles antibodies were present in 17 of 37 patients (46%); risk factors for seronegativity included younger age at transplant (p =.02) and greater time from transplant to testing (p =.04). Post‐transplant VZV antibodies were present in 17 of 39 patients (44%); risk factors for seronegativity included greater time from transplant to testing (p =.04). 6 of 16 patients (38%) who tested positive for pre‐transplant VZV antibodies tested negative after transplantation. Fourteen of 20 patients (70%) with at least 1 documented dose of the MMR vaccine tested positive for post‐transplant measles antibodies. Ten of 20 of patients (50%) with at least 1 documented dose of the VZV vaccine tested positive for post‐transplant VZV antibodies. We also describe 10 patients who received post‐transplant measles and VZV vaccines without documented complications. Conclusions: Our study suggests that pediatric LT patients are at greater risk of contracting measles and VZV despite vaccination status, and that prevalence of measles and VZV antibodies decreases as time from transplantation increases. This should weigh into the institutional risk–benefit assessment when deciding whether or not to administer LAVs to these patients. [ABSTRACT FROM AUTHOR]

Background: LAVV have historically been avoided in children after solid organ transplantation. However, it has been reported that post‐transplant, children without severe immunosuppression can generate anti‐varicella antibody after immunization but the duration of the response is not clear. Furthermore, the origin of the varicella virus in immunosuppressed patients who develop varicella after vaccination is often unclear. Clinical progress: A female child received LAVV 30 months after a living donor liver transplant at the age of 2 months. Varicella rash appeared on the trunk 16 days after vaccination and gradually spread over the body. The patient was treated with intravenous acyclovir followed by oral therapy and recovered fully. The virus detected in blisters was derived from the vaccine‐type strain. Paired sera before and after the onset of varicella showed an increase in antibody titer. However, 2 years after onset, the antibody titer decreased to undetectable again. Conclusions: This was an informative case of varicella due to vaccine strain attenuated virus. Antibody levels were not maintained over many years. Although varicella was caused by the vaccine‐type strain, repeated vaccinations may be necessary for post‐transplant patients who develop varicella. [ABSTRACT FROM AUTHOR]

Background: Historically, the IDSA and the AST have recommended that live vaccines not be administered post-transplant due to concern for induction of vaccinestrain disease in immunocompromised hosts. However, recent prospective studies and revised AST guidelines published in April 2019 suggest that in the current era of immunosuppression minimization, live vaccines may be safely administered to select transplant recipients with resulting immunoprotection. The goal of this study was to assess current post-transplant live vaccine practices at individual pediatric liver transplant centers following the updated AST guidelines. Methods: A six-item email survey detailing center-specific post-transplant live vaccine practices followed by up to three response-specific questions were distributed between July 2019 and May 2020 to a representative from each center participating in the SPLIT consortium. Results: The overall survey response rate was 93% (41/44 centers). Only 29% (12/41) of centers offer live vaccines post-transplant; each of these 12 centers uses different eligibility criteria for live vaccines. There was no difference between large (ten or more transplants per year) and small (less than ten transplants per year) centers in likelihood to offer live vaccines post-transplant. The main reasons for a center not offering post-transplant live vaccines were safety concerns and inability to reach group consensus. Conclusions: The majority of pediatric liver transplant centers are reluctant to offer live vaccines post-transplant despite the updated AST guidelines. Prospective multicenter studies are needed to confirm safety and immunogenicity of live vaccines post-transplant. [ABSTRACT FROM AUTHOR]

Reactivation of HSV and VZV is common following HSCT. Consensus guidelines do not support the use of routine screening for viremia following HSCT in adults, but no such clear guidelines exist in pediatrics. In our center, routine practice was to screen patients weekly for HSV and VZV viremia until engraftment in autologous transplant patients and up to day +100 in allogeneic transplant patients. We conducted a retrospective study of over 500 patients to establish whether this screening identified any patients with HSV or VZV viremia who would not have been identified by clinical signs or symptoms. Over a 4.5-yr period, routine screening identified three cases of HSV viremia and one case of VZV viremia. Two patients had persistent, unexplained fever and two patients had skin or mucosal lesions suggestive of HSV/ VZV. We conclude that routine screening for HSV and VZV viremia in pediatric HSCT patients has a very low yield and that viremia can be reliably identified by targeted testing in patients with vesicular skin lesions, oral or genital ulceration, unexplained fever, neurological symptoms, or unexplained abnormal liver transaminases. [ABSTRACT FROM AUTHOR]

Prelog M, Zimmerhackl LB. Varicella vaccination in pediatric kidney and liver transplantation. Pediatr Transplantation 2010: 14: 41–47. © 2009 John Wiley & Sons A/S. Reports about efficacy and safety of live-virus attenuated vaccines in patients before and after transplantation are mainly based on small patient numbers, making general recommendations for this patient population difficult. Children and adults as well as their close relatives and contact persons should be preferably immune to VZV before solid organ transplantation to avoid VZV-associated complications, thus making VZV vaccination necessary in susceptible individuals. The following literature review focused on efficacy and safety of VZV vaccination in pediatric kidney and liver transplant recipients. Review of literature also revealed that in all pediatric transplant candidates, humoral and cellular immunity against VZV should be consistently monitored to assess waning immunity under immunosuppressive treatment. This approach is desirable to estimate the risk of severe varicella disease after exposure in these patients. [ABSTRACT FROM AUTHOR]

Varicella infections pose serious challenges for organ transplant recipients. To determine the safety and immunogenicity of the OMVV and determine the maintenance of OMVV responses in transplanted subjects at varying periods of immunosuppression within the first two yr following transplantation. Eligible subjects given a two-dose OMVV pretransplantation were monitored for AE. Antibody levels were assessed at baseline, six wk post-OMVV, pretransplantation and up to 24 months post-transplantation. Seroprotection was defined as ≥5 gpEU. Twenty-one seronegative children were vaccinated. Following 42 doses, no vaccine-related serious AE occurred. Mab_titer were 17.8 (5.7–910.2) and 183.5 EU (18.8–8116.4) at six and 12 wk, respectively (p < 0.0001). Fourteen (66.7%) participants were transplanted at a median of 16 months (1.5–56) following OMVV and had Mab_titer of 27.2 EU (9.0–236.2) just prior to transplantation. Of 11 who had post-transplantation serology, seroprotection was sustained at three, six and 12 months post-transplantation in 10/11, 12/12 and 8/10 subjects. In five of six subjects with two-yr follow-up, antibody levels remained seroprotective. No breakthrough varicella infections occurred. The receipt of OMVV prior to transplantation induced humoral responses which persisted in the early months following transplantation and up to two yr post-transplantation and was not associated with any serious adverse consequences. [ABSTRACT FROM AUTHOR]

Infections represent a significant threat in solid-organ recipients. However, a certain number of infections can be prevented by immunizing patients before their transplantation. The aim of this study is to determine the level of immunity of children undergoing liver transplantation and to assess their capacity to maintain protective levels after surgery. Charts of 44 children transplanted with deceased donation livers between 1990 and 2002 at the Children's Hospital of Geneva were reviewed. Vaccine antibody responses were established pre- and post-transplantation. Only 43% of patients were up to date for diphtheria, tetanus, acellular pertussis, and polio vaccines at the pretransplantation visit, while 44% of children older than 12 months had received their required measles-mumps-rubella vaccines. Six of 44 children had received at least one dose of hepatitis B vaccine, while only two patients had received at least one dose of hepatitis A vaccine. After immunization, and one yr after transplantation, only 14 of 44 patients had detectable anti-HBs antibodies and seven of 18 had anti-HAV antibodies. Varicella antibodies were undetectable in 15 of 19 patients immunized prior to transplantation. This study highlights the need to enforce vaccination before transplantation, follow-up on vaccine- induced immunity, and adapt vaccination schedules after liver transplantation in children, especially for non-live vaccines, which are universally recommended in this population. [ABSTRACT FROM AUTHOR]

Infections by herpesviruses may have severe complications in liver transplant patients. Although prophylactic varicella zoster virus vaccination is strongly recommended and widely applied, severe infection may still occur. We report the case of systemic chronic varicella, which developed in a liver allograft recipient, unresponsive to antiviral drug treatment, successfully treated by varicella zooster-specific CTL. Graft failure ensued, likely, because of massive cytolysis of infected hepatocytes. The patient, who was re-transplanted in the absence of signs of varicella zooster reactivation, is now well and disease free 3 yr after second liver transplant. [ABSTRACT FROM AUTHOR]

Viral infection is a recognized and potentially serious complication in children following solid organ transplantation. The risks of viral infection are particularly important for infants who may not have completed standard childhood immunizations at the time of transplantation and are therefore at risk for otherwise preventable infections. The general practice of withholding live virus immunization from transplant recipients has been questioned and several small studies have looked at MMR and/or Varivax administration in children following transplantation. This retrospective study analyzes the response to primary MMR and varicella immunization in selected pediatric liver transplant recipients in the largest such study to date. Nineteen of 26 children (73%) developed serologic immunity for measles following MMR (although 18 required multiple doses). Similarly, varicella immunization resulted in seroconversion in 20 of 31 children (64.5%; seven required multiple doses). Only minor adverse effects reported in the general population were observed. Live virus immunization with MMR and Varivax was safe and immunogenic in this selected population of liver transplant recipients. [ABSTRACT FROM AUTHOR]

Warmington L, Lee BE, Robinson JL. Loss of antibodies to measles and varicella following solid organ transplantation in children.Pediatr Transplantation 2005.© 2005 Blackwell MunksgaardThe objective of this study was to determine if loss of antibodies to measles and to varicella occurs in pediatric solid organ transplant recipients. Antibodies were measured in eight hepatic, four cardiac, and six renal transplant patients who had antibodies to measles prior to transplantation, and in six hepatic, five cardiac, and seven renal transplant patients who had antibodies to varicella prior to transplantation. Within 6 months of the transplant, loss of antibodies occurred in four of 18 patients who were seropositive for measles prior to transplantation (22.2%) and in two of 18 patients who were seropositive for varicella prior to transplantation (11.1%). In conclusion, serology for measles and varicella should be considered annually following solid organ transplantation so that appropriate advice can be given to patients who have seroreverted. [ABSTRACT FROM AUTHOR]

Abstract: Existing studies support the use of varicella vaccine in a two-dose regimen in patients with renal disease prior to transplantation. Levels of anti-varicella zoster virus antibody should be monitored on a regular basis after immunization, and where a loss of a previously protective antibody titer occurs, a third booster dose should be considered pretransplant. Further data need to be collected regarding the use of the vaccine in seronegative patients who have already undergone transplantation. [ABSTRACT FROM AUTHOR]

Abstract: Because of the severe complications that may result from varicella zoster virus (VZV) infection following renal transplantation (Tx), transplanted varicella-susceptible children exposed to varicella are typically given varicella zoster immunoglobulin (VZIG) as prophylaxis or are admitted and treated with parenteral acyclovir if VZIG prophylaxis fails. As both VZIG and hospitalization are costly, prevention of varicella infection by vaccination could potentially result in significant cost savings in addition to decreasing morbidity and mortality. To test this hypothesis, we developed a decision-analysis model to evaluate the cost-effectiveness of vaccinating patients with chronic renal failure (CRF) against varicella prior to renal transplant. Under baseline assumptions, vaccination for varicella pretransplant was a cost-effective strategy, with a cost of $211 per patient vaccinated compared with $1,828 per patient not vaccinated. The magnitude of cost savings from vaccination was sensitive to variations in the cost of varicella vaccine, the percentage of patients hospitalized for treatment with acyclovir, and the percentage of patients exposed to varicella infection. One- and two-way sensitivity analyses confirmed that vaccination was the dominant cost-effective strategy under all conditions examined. We conclude that vaccination for varicella pretransplant is cost-effective for patients with CRF, and that the magnitude of cost savings is sensitive to the cost of hospitalization, the percentage of patients exposed to varicella, and the cost of varicella vaccination. Pending results of ongoing studies of the safety and efficacy of VZV vaccine in children with CRF, we recommend that VZV vaccine be given to all children with CRF. [ABSTRACT FROM AUTHOR]

Varicella and measles infection represents a significant source of morbidity and mortality for pediatric LT recipients. We evaluated the prevalence and correlates of post‐transplant immunity in pediatric LT recipients previously immunized against measles (n = 72) and varicella (n = 67). Sixteen of seventy‐two (22%) patients were measles non‐immune, and 42/67 (63%) were varicella non‐immune after LT. Median time from LT to titers for measles and varicella was 4.0 and 3.3 years, respectively. In the measles cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.026) and were younger at both time of vaccination (P = 0.006) and LT (P = 0.004) compared with immune patients. Upon multivariable analysis, weight > 10 kg at LT (OR 5.91, 95% CI 1.27‐27.41) and technical variant graft (OR 0.07, 95% CI 0.01‐0.37) were independently, significantly associated with measles immunity. In the varicella cohort, non‐immune patients received fewer pretransplant vaccine doses (P = 0.028), were younger at transplant (P = 0.022), and had less time lapse between their last vaccine and transplant (P = 0.012) compared with immune patients. Upon multivariate analysis, time > 1 year from last vaccine to LT was independently, significantly associated with varicella immunity (OR 3.78, CI 1.30‐11.01). This study demonstrates that non‐immunity to measles and varicella is a prevalent problem after liver transplantation in children and identifies 3 unique risk factors for non‐immunity in this high‐risk population. [ABSTRACT FROM AUTHOR]