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Background: LT is an elective treatment choice for children diagnosed with GSD1b that can improve their quality of life and stabilize their glucose intolerance. However, careful attention should be paid to immunosuppression after LT due to the susceptibility to infection because of neutropenia and neutrophil dysfunction in GSD1b patients. This study revealed the immunological features and complications in the early post-LT period., Methods: We compared findings between 11 (1.9%) children with GSD1b and 273 children with BA. Analyses using the PSM were performed to overcome selection bias., Results: Despite persistent low tacrolimus trough levels in GSD1b patients, none of these children developed TCMR within 1 month after LDLT (GSD1b: 0/11 [0%] vs. BA: 86/273 [31.5%], p = .038). This result was also confirmed in PSM. The incidence of bloodstream infections was higher in GSD1b patients than in BA patients in the early phase of the post-transplant period (GSD1b: 4/11 [36.4%] vs. BA: 33/273 [12.1%], p = .041), but not reach statistical significance in PSM. In a phenotypic analysis, the ratio of CD8 + T cells in GSD1b recipients' peripheral blood mononuclear cell samples was lower than in recipients with BA through the first month after LDLT., Conclusions: We found that GSD1b recipients were more likely to develop postoperative bloodstream infection than recipients with BA but did not experience TCMR despite low tacrolimus levels in the early post-LDLT period. A tailored immunosuppression protocol should be prepared for GSD1b recipients after LDLT., (© 2021 Wiley Periodicals LLC.)

Methicillin-resistant Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric liver transplant (LT) recipients. Physiological changes following LT may affect vancomycin pharmacokinetics; however, appropriate dosing to achieve sufficient drug exposure (i.e., 24-h area under the concentration-time curve [AUC 24 ]/MIC ≥ 400) in pediatric LT recipients has not been reported. This retrospective pharmacokinetics study of LT recipients aged <18 years utilized data on patient characteristics with vancomycin concentrations and dosing information obtained from electronic medical records. Population pharmacokinetics analysis was conducted by nonlinear mixed-effects modeling with the Phoenix NLME software. Potential covariates were screened with univariate and multivariate analysis. Monte Carlo simulations were performed using the final model to explore appropriate dosing. The study included 270 pharmacokinetics profiles encompassing 1,158 concentrations measured in 161 patients. The median age was 13.3 (interquartile range, 7.6 to 53.5) months, serum creatinine (sCr) was 0.16 (0.12 to 0.23) mg/dl, and days from LT (DFLT) was 17 (6 to 31). Multivariate analysis demonstrated that lower sCr and shorter DFLT were associated with higher clearance. By post hoc estimation, the average clearance and volume of distribution were 0.18 liters/h/kg and 1.01 liters/kg, respectively. The Monte Carlo simulations revealed that only 16% of patients achieved an AUC 24 /MIC of ≥400 with the assumed vancomycin MIC of 1 μg/ml. DFLT and sCr were significant covariates for vancomycin clearance in pediatric LT recipients. Standard vancomycin dosing may be insufficient, and higher or more frequent dosing may be required to achieve an AUC 24 /MIC of ≥400 in pediatric LT recipients with normal renal function. IMPORTANCE We evaluated vancomycin pharmacokinetics in pediatric LT recipients and developed a population pharmacokinetics model by considering various factors that might account for alterations in vancomycin pharmacokinetics. Our analyses revealed that lower serum creatinine levels and a shorter duration from the day of LT were associated with higher vancomycin clearance and led to subtherapeutic drug exposure. We also performed Monte Carlo simulations to determine the appropriate dosing strategy in pediatric LT recipients, which revealed that a standard vancomycin dosing might be insufficient and that higher or more frequent dosing might be necessary to achieve an AUC 24 /MIC of ≥400 in pediatric LT recipients with normal renal function. To the best of our knowledge, this is the first study to assess vancomycin pharmacokinetics in pediatric LT recipients by population pharmacokinetics analysis.

Recent guidelines suggest that LAVs may be given to LT recipients meeting certain criteria. However, information is still limited. We sought to evaluate the safety of LAVs, including measles, mumps, rubella, and varicella to LT recipients following our clinically based immunization protocol for LT recipients. We conducted a case-series analysis on safety of LAVs for measles, rubella, varicella, and mumps given to LT recipients at our institution from July 2010 to July 2019. Patients who underwent LT at age <20 years who visited our immunization clinic were included. LT recipients were vaccinated if 2 years had lapsed from LT, had no signs of rejection within 6 months, and were on minimal immunosuppressants. Patient demographics, underlying diseases, type and number of vaccines administered, date of vaccination, and adverse events occurring within 4 weeks after vaccination were extracted from their medical records. During the study period, LAVs were administered 422 times to 209 patients who met criteria and included 225 doses of MR combination vaccine, 224 doses of varicella vaccine, and 215 doses of mumps vaccine. Underlying diseases included cholestatic liver diseases (n = 125), followed by metabolic diseases (n = 33) and acute liver failure (n = 19). Nine non-critical adverse events (2.1%) possibly associated with LAVs were reported, but there were no serious adverse events, including hospitalizations or deaths. In conclusion, LAVs administered to LT recipients were safe without any serious adverse events following our relatively simple institutional protocol., (© 2020 Wiley Periodicals LLC.)

Competing Interests: The authors declare no funding or conflicts of interest.

Background: The strategy to eradicate polio is based on preventing infection by immunizing all children until the world is polio-free. However, data regarding efficacy of polio-containing vaccination in immunocompromised patients such as LT recipients are limited., Methods: We conducted an observational study at the largest pediatric transplant center in Japan from January 2011 to January 2015. LT recipients were enrolled after transplantation, and those who had completed the Japanese polio vaccination program were eligible for the study. Patients' demographics were collected from their medical records. Antibody titers against poliovirus serotypes 1-3 were measured using the neutralization test at the routine follow-up visits after enrollment. Factors associated with seropositivity against each type of poliovirus were evaluated., Results: Sixty-four patients who had received the complete polio vaccination series were enrolled in the study. Of these, 37 patients had received all series of polio-containing vaccination before LT. Median age of the patients was 75 months. Their underlying diseases included the following: 40 (63%) with cholestatic liver diseases and 11 (17%) with metabolic disorders. After a median interval of 43 months after LT, seropositivity rates against poliovirus 1, 2, and 3 were 93.8% (60/64), 92.2% (59/64), and 54.7% (35/64), respectively. Among 32 patients who had received only oral polio vaccine (OPV), seropositivity against poliovirus 3 was particularly low (25.0%). No factors associated with seropositivity against each type of poliovirus were identified., Conclusions: In the LT recipients, seropositivity for poliovirus 3 was low, suggesting a need for additional inactivated polio-containing vaccination after LT, especially for patients who had received only OPV., (© 2020 Wiley Periodicals LLC.)

Background: Bloodstream infection (BSI) is a major cause of morbidity and mortality after pediatric liver transplantation (LT). However, most studies have focused on BSI occurring within a few months after LT. In this study, we evaluated the characteristics of BSI occurring beyond 6 months after pediatric LT., Methods: We conducted a retrospective cohort study at a pediatric LT center in Japan from November 2005 to March 2016. We evaluated the causative organisms and site of late-onset BSI in children ≤ 18 years of age. The risk factors for developing late-onset BSI and the associations of late-onset BSI with long-term outcomes were also evaluated., Results: Three hundred forty cases of LT were evaluated. Thirty-eight BSI developed in 29 (9%) LT recipients. There were 42 organisms (nine Gram-positive cocci, 33 Gram-negative rods) isolated from the blood cultures of recipients with late-onset BSI. The most frequent sites of late-onset BSI was intraabdominal infection (18/38; 47%). There were also 14 (39%) episodes with no apparent focus. In multivariate analysis, a prolonged operative time > 12 hours (odds ratio [OR] = 3.55; P = 0.04) and biliary stenosis (OR = 4.60; P = 0.006) were independent risk factors for developing late-onset BSI. Late-onset BSI was associated with increased retransplantation rate (P = 0.04) and mortality (P < 0.001)., Conclusion: Late-onset BSI developed in 9% of recipients after pediatric LT. Gram-negative rods accounted for the majority of late-onset BSI as a consequence of abdominal infection, but the focus was often unclear. Prolonged operative time at LT and biliary stenosis were independent risk factors for developing late-onset BSI.

Background: Cytomegalovirus (CMV) is one of the most common causes of infection after solid organ transplantation with symptomatic disease occurring at an incidence of 20% to 40% without preventative measures. Although CMV donor+/recipient - serostatus is well known to be a risk factor, there is little data about other risk factors for CMV infection in the setting of pediatric liver transplantation (LT). We hypothesized that fulminant hepatic failure (FHF) may be a risk factor for CMV infection given anecdotal reports of complications associated with FHF., Methods: We conducted medical chart review of children who underwent LT at a tertiary children's hospital in Tokyo between November 2005 and October 2015. We evaluated the risk factors, especially FHF, and prognosis for CMV infection under preemptive therapy., Results: Three hundred thirty-seven living donor LT were analyzed. Underlying diseases were cholestatic liver disease (n = 172, 51%), metabolic disease (n = 59, 18%), and FHF (n = 51, 15%). Among 337 LT, 147 (44%) recipients developed CMV antigenemia. In multivariate analysis, FHF (odds ratio, 4.99; 95% confidence interval, 1.86-13.40; P = 0.001) and CMV serostatus were independent risk factors for developing CMV antigenemia. Positive donor serostatus was significantly associated with development of antigenemia within 1-year post-LT regardless of recipient serostatus (P <0.001). On the other hand, positive recipient status was associated with CMV antigenemia in the first 21 days (P <0.001). Only 12 (3.6%) of 337 children developed CMV disease., Conclusions: Fulminant hepatic failure was found to be a risk factor for CMV infection independent of CMV serostatus.

Background: Postoperative bloodstream infection (BSI) is the most important determinant of recipient morbidity and mortality after liver transplantation (LT). Children who underwent LT are at the highest risk of developing BSI because of the significant surgical intervention, use of multiple devices, and administration of immunosuppressive agents. However, information regarding the risk factors for BSI in children after LT is limited., Methods: We retrospectively reviewed 210 children who underwent living-donor LT at the largest pediatric LT center in Japan. Patients' characteristics, blood culture results and clinical outcomes were extracted from electronic medical records. Univariate and multivariate analyses were performed to identify the risk factors for BSI., Results: Among the 210 LT recipients, 53 (25%) recipients experienced 86 episodes of BSI during the observational period. The source of the BSI was identified only in 38%: catheter-related BSI (27%) peritonitis (7%), urinary tract infection (2%), pneumonia (1%) and infectious endocarditis (1%). A multivariate analysis demonstrated that body weight (P = 0.03), volume of blood loss during LT (P < 0.001) and cytomegalovirus (CMV) antigenemia positivity (P = 0.04) were independently associated with the development of BSI. The risk factors for BSI differed when we analyzed the subjects according to age (≤24 months and >24 months), blood loss and pediatric end-stage liver disease/model for end-stage liver disease versus positive CMV antigenemia., Conclusions: The volume of blood loss, postoperative CMV antigenemia positivity and body weight were associated with the development of BSI after LT in pediatric living-donor recipients. To identify the age-specific predictors of BSI in children who underwent LT, age-specific analyses are crucial.

After liver transplantation (LT), live attenuated vaccines (LAVs) are generally contraindicated. LAVs are recommended before LT for patients ≥ 6 months of age. However, the evidence supporting this practice is limited. Patients were enrolled before and after LT. Clinical data for patients were obtained from medical records. Serum antibody titers were evaluated at the time of enrollment and prospectively. Serum antibody titers were measured with a hemagglutination inhibition test for measles and rubella and with an enzyme-linked immunosorbent assay for varicella and mumps. Univariate and multivariate analyses were performed to investigate the factors that affect the serostatus. Serological analyses of 49 patients immunized before LT (median age, 45 months; male, 35%) were performed. Underlying diseases were biliary atresia (n = 27; 55%), metabolic diseases (n = 13; 27%), fulminant hepatic failure (n = 5; 10%), and others (n = 4; 8%). The seropositivity rate after each vaccine was 46.9% (measles), 89.4% (rubella), 67.5% (varicella), and 48.8% (mumps). Factors independently associated with seronegativity were a vaccination age < 12 months for measles (P = .002), a lower body weight for varicella (P = 0.01), and underlying diseases other than biliary atresia for mumps (P = .004). No serious adverse event was observed during the study period. The immunogenicity of LAVs before LT was high for rubella but low for the others. Before LT, further vaccination strategies are needed for patients. In addition, serological follow-up may be indicated for patients with factors associated with seronegativity., (© 2015 American Association for the Study of Liver Diseases.)

Immunizations using live-attenuated vaccines are not recommended for post-liver transplant children due to its theoretical risks. However, they will encounter vaccine-preventable viral diseases upon returning to real-life situations. We performed a total of 70 immunizations with four individual live-attenuated vaccines to 18 pediatric post-living donor liver transplant (LDLT) recipients who fulfilled a clinical criteria including humoral and cell-mediated immunity. The seroconversion rates at the first dose for measles (strain AIK-C), rubella (strain TO-336), varicella (strain Oka), and mumps (strains Hoshino) were 100% (15/15), 100% (15/15), 82% (9/11), and 82% (9/11), respectively. During observed period (-5 years 11 months), a few cases with waning immunity (antibodies were once produced but the levels fell over time) were seen except after rubella immunization. Clinical diseases after seroconversion or definite serious adverse effects due to immunization were not observed. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed.

We report on an 8‐year‐old girl with Wilson disease who developed three episodes of peritonitis due to extended‐spectrum beta‐lactamase‐producing Escherichia coli after liver transplantation. Massive ascites were thought to account for low meropenem concentrations with standard dosing. Extending the infusion achieved higher troughs, greater time above minimum inhibitory concentration. [ABSTRACT FROM AUTHOR]