Pediatric Liver Transplantation Research Articles

Modified patch-conduit venoplasty for portal vein hypoplasia in pediatric liver transplantation.

Portal vein (PV) interposition can induce various PV-related complications, making more reliable techniques necessary. The present study describes the development of a modified patch venoplasty technique, combining the native PV wall and a vein homograft conduit, called modified patch-conduit venoplasty (MPCV). The surgical technique for MPCV was optimized by simulation and applied to seven pediatric patients undergoing liver transplantation (LT) for biliary atresia combined with PV hypoplasia. The simulation study revealed that inserting the whole-length native PV wall as a longitudinal rectangular patch was more effective in preventing PV conduit stenosis than the conventional technique using triangular partial insertion. These findings were used to develop the MPCV technique, in which the native PV wall was converted into a long rectangular patch, acting as a backbone for PV reconstruction. A longitudinal incision on the vein conduit converted the cylindrical vein into a large vein patch. The wall of the native PV was fully preserved as the posterior wall of the PV conduit, thus preventing longitudinal redundancy and unwanted rotation of the reconstructed PV. This technique was applied to seven patients with biliary atresia undergoing living-donor and deceased-donor split LT. None of these patients has experienced PV complications for up to 12 months after transplantation. This newly devised MCPV technique can replace conventional PV interposition. MCPV may be a surgical option for reliable PV reconstruction using fresh or cryopreserved vein homografts during pediatric LT.

Determinants of early surgical complications after pediatric liver transplantation: A single center/single surgeon experience over 20 years.

The risk of early surgical complications of liver transplantation (LT) is higher in children when compared with adults. The aims of the present retrospective study from a single center cohort/single surgeon were to identify the predictive factors for surgical complications after pediatric LT. All children receiving a first LT from October 1990 to October 2010 in our center were included. Included 151 children (boys 55.0%), with a mean age of 4.8±4.8 years, and a mean weight of 17.9±14.4kg. Thirty-seven patients were transplanted within the first year, and 59 patients had a body weight below 10kg. The main initial liver disease was biliary atresia (49.0%). Living donor LT was performed in 39 cases (25.8%), cadaveric whole liver LT in 50 cases (33.1%), and cadaveric partial liver LT in 62 cases (41.1%). Early surgical complications included reoperation (37.8%), vascular complications (8.6%), i.e. arterial (3.3%) or portal thrombosis/stenosis (7.3%) within the first month, and biliary complications in the first 90 days occurred in 22.5% of the cases. The main indications for surgical revision were abdominal bleeding, treatment of a biliary complication, and bowel perforation. Multivariate analysis disclosed that only graft type (split and moreover from a living donor) was significantly and independently associated with the occurrence of biliary complication, and that indication for LT, period, graft type, and operative time were significantly and independently associated with the necessity of surgical revision. Our results emphasize that surgical complications are frequent and strongly depend on patient/graft characteristics.

Renal Involvement After Pediatric Liver Transplantation: A Large Single-Center Cohort

Renal Involvement After Pediatric Liver Transplantation: A Large Single-Center Cohort

Revisiting Clinical Relevance of Radionucleotide-Based GFR Estimation and Comparison with CKiD U25 eGFR Equation in Pediatric Liver Transplant Patients

Revisiting Clinical Relevance of Radionucleotide-Based GFR Estimation and Comparison with CKiD U25 eGFR Equation in Pediatric Liver Transplant Patients

Pharmacokinetics and therapeutic target attainment of vancomycin in pediatric post-liver transplant patients

IntroductionVancomycin is widely prescribed to treat or prevent Gram-positive infections in pediatric liver transplant recipients. The objective of this prospective cohort study is to describe vancomycin pharmacokinetics and to evaluate the therapeutic target attainment after initial dose regimen. Materials and methodsPatients with previous renal injury were excluded. Vancomycin therapy started with 40‒60 mg/kg/day. The pharmacokinetic parameters were assessed using two steady-state blood samples and the first-order kinetic equations. Therapeutic target was defined as vancomycin 24-hour Area Under the Curve/Minimum Inhibitory Concentration (AUC/MIC) ≥ 400 and < 600. ResultsSixteen patients were included. The found vancomycin clearance, half-life, and volume of distribution were, respectively: 2.1 (1.3‒2.8) mL/kg/min, 3.3 (2.7‒4.4) hours, and 0.7 (0.5‒0.9) L/kg. With the initial dose, only 6 (37 %) patients reached the therapeutic target against Gram-positive pathogens with MIC 1 mg/L. After individual dose adjustments, all patients reached the target. The correlation between trough levels and AUC was low (R2 = 0.5). ConclusionsPediatric patients with preserved renal function after liver transplantation have an increased volume of distribution for vancomycin, and most patients present subtherapeutic levels after the standard initial dosing regimen. With the vancomycin AUC-guided monitoring and dosing, it is possible to improve therapeutic target attainment.

Evaluation of Newborn Direct Bilirubin As Screening for Cholestatic Liver Disease.

Biliary atresia (BA) remains the most common indication for pediatric liver transplantation. Early diagnosis is essential for a favorable long-term prognosis for patients with BA. Preliminary data suggests that measurement of direct bilirubin (DB) in newborns may be an effective screening tool for neonatal cholestasis, particularly BA, allowing for early referral and diagnosis. The objective of our study was to establish a cutoff DB value to predict diagnosis of cholestatic liver disease (CLD) with high sensitivity and specificity, as well as, to evaluate whether newborns with elevated DB received appropriate follow-up in our health system. Baseline data were collected on infants born between 2016 and 2019 who had serum total bilirubin and DB drawn in the nursery, and who continued to follow in our health system. Sensitivity, specificity, and positive and negative predictive values were examined using cutoff values of 0.5, 0.6, and 0.7 mg/dL for identifying infants at risk for CLD. Patients' charts were reviewed to note whether they had follow-up levels drawn by their pediatrician or by the hepatology team within 2 months of age and whether they were diagnosed with CLD. Serum total bilirubin and DB levels were drawn from 11 965 infants during their hospitalizations. Three infants from this cohort were diagnosed with CLD: 2 with BA and 1 with Alagille syndrome. DB cutoff values of 0.5, 0.6, and 0.7 mg/dL had sensitivity of 100% and specificity of 96.83% (95% confidence interval [CI], 96.69%-97.53%), 99.08% (95% CI, 98.81%-99.30%), and 99.63% (95% CI, 99.4%-99.7%), respectively. Given that a DB of 0.6 mg/dL had a sensitivity of 100% and specificity of 99%, this value was chosen as the cutoff value to monitor for DB follow-up and diagnosis of CLD. Out of 60 infants who met criteria for DB ≥0.6 mg/dL, only 15 (25%) had a repeat level drawn after nursery discharge; 3 (5%) were eventually diagnosed with CLD. A DB cutoff value of 0.6 mg/dL yielded high sensitivity and specificity for identifying patients with CLD. All 3 patients diagnosed with CLD had elevated DB at hospital discharge. The data revealed that the majority (75%) of eligible newborns did not receive follow-up for their elevated DB in the outpatient setting.

Percutaneous creation of a biliary enteric neo-anastomosis in a pediatric liver transplant patient using a vascular re-entry device

Percutaneous creation of a biliary enteric neo-anastomosis in a pediatric liver transplant patient using a vascular re-entry device

Ambient air pollution is associated with graft failure/death in pediatric liver transplant recipients

Children exposed to disproportionately higher levels of air pollution experience worse health outcomes. In this population-based, observational registry study, we examine the association between air pollution and graft failure/death in children following liver transplantation (LT) in the US. We modeled the associations between air pollution (PM2.5) levels localized to the patient’s ZIP code at the time of transplant and graft failure or death using Cox proportional-hazards models in pediatric LT recipients aged <19 years in the US from 2005-2015. In univariable analysis, high neighborhood PM2.5 was associated with a 56% increased hazard of graft failure/death (HR: 1.56; 95% CI: 1.32, 1.83; P < .001). In multivariable analysis, high neighborhood PM2.5 was associated with a 54% increased risk of graft failure/death (HR: 1.54; 95% CI: 1.29, 1.83; P < .001) after adjusting for race as a proxy for racism, insurance status, rurality, and neighborhood socioeconomic deprivation. Children living in high air pollution neighborhoods have an increased risk of graft failure and death posttransplant, even after controlling for sociodemographic variables. Our findings add further evidence that air pollution contributes to adverse health outcomes for children posttransplant and lay the groundwork for future studies to evaluate underlying mechanisms linking PM2.5 to adverse LT outcomes.

Postoperative Bloodstream Infection Is Associated with Early Vascular Complications in Pediatric Liver Transplant Recipients with Biliary Atresia.

Bloodstream infection (BSI) after pediatric liver transplantation (PLT) is a common and severe complication that affects patient survival. Children with biliary atresia (BA) are at an increased risk for clinically significant infections. This study evaluated the impact of post-PLT BSI on clinical outcomes in children with BA. A total of 67 patients with BA aged <18 years who underwent PLT between April 2006 and September 2020 were analyzed and divided into two groups according to the occurrence of post-PLT BSI within 1 month (BSI vs. no BSI = 13 [19.4%] vs. 54 [80.6%]). The BSI group was significantly younger at the time of PLT and had a higher frequency of BSI at the time of PLT than the no BSI group. Early vascular complications within 3 months and reoperations were significantly more frequent in the BSI group. Univariate and multivariate analyses revealed that bacteremia within 1 month of PLT and graft-to-recipient weight ratio >4% were significantly associated with vascular complications. In conclusion, BSI after PLT is associated with increased vascular complications and reoperations. Proper control of bacterial infections and early liver transplantation before uncontrolled BSI may reduce vascular complications and unexpected reoperations in children with BA.

Development and validation of a nomogram to predict allograft survival after pediatric liver transplantation.

Liver transplantation is the main treatment for cholestatic liver disease and some metabolic liver diseases in children. However, no accurate prediction model to determine the survival probability of grafts prior to surgery exists. This study aimed to develop an effective prognostic model for allograft survival after pediatric liver transplantation. This retrospective cohort study included 2032 patients who underwent pediatric liver transplantation between January 1, 2006, and January 1, 2020. A nomogram was developed using Cox regression and validated based on bootstrap sampling. Predictive and discriminatory accuracies were determined using the concordance index and visualized using calibration curves; net benefits were calculated for model comparison. An online Shiny application was developed for easy access to the model. Multivariable analysis demonstrated that preoperative diagnosis, recipient age, body weight, graft type, preoperative total bilirubin, interleukin-1β, portal venous blood flow direction, spleen thickness, and the presence of heart disease and cholangitis were independent factors for survival, all of which were selected in the nomogram. Calibration of the nomogram indicated that the 1-, 3-, and 5-year predicted survival rates agreed with the actual survival rate. The concordance indices for graft survival at 1, 3, and 5 years were 0.776, 0.757, and 0.753, respectively, which were significantly higher than those of the Pediatric End-Stage Liver Disease and Child-Pugh scoring systems. The allograft dysfunction risk of a recipient could be easily predicted using the following URL: https://aspelt.shinyapps.io/ASPELT/ / CONCLUSION: The allograft survival after pediatric liver transplantation (ASPELT) score model can effectively predict the graft survival rate after liver transplantation in children, providing a simple and convenient evaluation method for clinicians and patients.

Long-term Outcome of Asymptomatic Patients With Graft Fibrosis in Protocol Biopsies After Pediatric Liver Transplantation.

The histological prevalence of allograft fibrosis in asymptomatic children after liver transplantation (LT) is well documented. However, long-term graft and patient survival remain unclear. This retrospective multicenter study aims to determine the prevalence of allograft fibrosis and analyze the long-term outcome for patients transplanted in childhood. We reviewed clinical data of children who had undergone 10-y protocol liver biopsies. We excluded patients with autoimmune hepatitis, primary sclerosing cholangitis, hepatitis B or C, and retransplantation. In total, 494 patients transplanted in childhood across 12 international transplant centers were included. We evaluated the development of fibrosis by comparing the results with biopsies obtained 5 and 15 y post-LT. Histological findings were correlated with graft and patient survival up to 20 y post-LT. In the 10-y biopsies, periportal or pericentral fibrosis was observed in 253 patients (51%), 87 (18%) had bridging fibrosis, 30 (6%) had cirrhosis, and 124 (25%) had no fibrosis. The prevalence and stage of graft fibrosis significantly progressed from 5 to 10 y. At 10 y, the severity of fibrosis correlated significantly with inflammation. Patients with graft cirrhosis in the 10-y biopsy were more likely to die or require retransplantation subsequently ( P = 0.027). At 10 y post-LT, most patients transplanted in childhood developed fibrosis, based on the protocol liver biopsies. Although mild-to-moderate graft fibrosis did not largely affect patient or graft survival up to 20 y post-LT, this progressive fibrosis finding has substantial implications for developing cirrhosis and portal hypertension in adult care.

Vascular thrombosis after pediatric liver transplantation: Is prevention achievable?

BackgroundVascular thromboses (VT) are life-threatening events after pediatric liver transplantation (LT). Single-center studies have identified risk factors for intra-abdominal VT, but large-scale pediatric studies are lacking. MethodsThis multicenter retrospective cohort study of isolated pediatric LT recipients assessed pre- and perioperative variables to determine VT risk factors and anticoagulation-associated bleeding complications. ResultsWithin seven postoperative days, 31/331 (9.37%) patients developed intra-abdominal VT. Open fascia occurred more commonly in patients with VT (51.61 vs 23.33%) and remained the only independent risk factor in multivariable analysis (OR = 2.84, p = 0.012). Patients with VT received more blood products (83.87 vs 50.00%), had significantly higher rates of graft loss (22.58 vs 1.33%), infection (50.00 vs 20.60%), and unplanned return to the operating room (70.97 vs 16.44%) compared to those without VT. The risk of bleeding was similar (p = 0.2) between patients on and off anticoagulation. ConclusionsProphylactic anticoagulation did not increase bleeding complications in this cohort. The only independent factor associated with VT was open fascia, likely a graft/recipient size mismatch surrogate, supporting the need to improve surgical techniques to prevent VT that may not be modifiable with anticoagulation.

Biliary Leak after Pediatric Liver Transplantation Treated by Percutaneous Transhepatic Biliary Drainage-A Case Series.

Biliary leaks are a severe complication after pediatric liver transplantation (pLT), and successful management is challenging. The aim of this case series was to assess the outcome of percutaneous transhepatic biliary drainage (PTBD) in children with bile leaks following pLT. The necessity of additional percutaneous bilioma drainage and laboratory changes during therapy and follow-up was documented. All children who underwent PTBD for biliary leak following pLT were included in this consecutive retrospective single-center study and analyzed regarding site of leak, management of additional bilioma, treatment response, and patient and transplant survival. The courses of inflammation, cholestasis parameters, and liver enzymes were retrospectively reviewed. Ten children underwent PTBD treatment for biliary leak after pLT. Seven patients presented with leakage at the hepaticojejunostomy, two with leakage at the choledocho-choledochostomy and one with a bile leak because of an overlooked segmental bile duct. In terms of the mean, the PTBD treatment started 40.3 ± 31.7 days after pLT. The mean duration of PTBD treatment was 109.7 ± 103.6 days. Additional percutaneous bilioma drainage was required in eight cases. Bile leak treatment was successful in all cases, and no complications occurred. The patient and transplant survival rate was 100%. CRP serum level, leukocyte count, gamma-glutamyl transferase (GGT), and total and direct bilirubin level decreased significantly during treatment with a very strong effect size. Additionally, the gamma-glutamyl transferase level showed a statistically significant reduction during follow-up. PTBD is a very successful strategy for bile leak therapy after pLT.

Development of a predictive nomogram for switching immunosuppressive drugs in pediatric liver transplant recipients

BackgroundTacrolimus (TAC) is the preferred calcineurin inhibitor (CNI) for pediatric liver transplant recipients. However, some recipients may not achieve the desired therapeutic window concentration of TAC, leading to poor prognosis. This study aimed to develop a clinical model that can predict the effectiveness of TAC in pediatric liver transplant recipients and help clinicians quickly identify cyclosporin as an alternative.MethodsWe retrospectively analyzed data from 2,032 pediatric liver transplant recipients who underwent surgery at Renji Hospital, Shanghai Jiaotong University School of Medicine between 2006 and 2019. Demographic, comorbidity and pre-operative laboratory data were collected, and a nomogram was constructed using multivariate logistic regression analysis to estimate the risk of poor therapeutic outcomes for TAC-based immunosuppression.ResultsThe constructed nomogram included seven parameters, namely recipient CYP3A4 genotype, pre-transplant cholangitis, GRWR, spleen long diameter, serum albumin, graft volume reduction, and donor CYP genotype. The nomogram showed good discriminative ability with an area under the receiver operating characteristic curve (AUC) of 74.5% and good calibration. Decision curve analysis indicated a high potential clinical application of the model.ConclusionThis simple clinical model effectively predicts the risk of poor therapeutic outcomes in pediatric liver transplant recipients who receive TAC-based immunosuppression. Clinicians can use the model to identify cyclosporin as an alternative quickly, potentially improving patient prognosis.

Current status and future directions of liver transplantation for metabolic liver disease in children.

Orthotopic liver transplantation (OLT) in the care of children with inborn errors of metabolism (IEM) is well established and represent the second most common indication for pediatric liver transplantation in most centers worldwide, behind biliary atresia. OLT offers cure of disease when a metabolic defect is confined to the liver, but may still be transformative on a patient's quality of life reducing the chance of metabolic crises causing neurological damage in children be with extrahepatic involvement and no "functional cure." Outcomes post-OLT for inborn errors of metabolism are generally excellent. However, this benefit must be balanced with consideration of a composite risk of morbidity, and commitment to a lifetime of post-transplant chronic disease management. An increasing number of transplant referrals for children with IEM has contributed to strain on graft access in many parts of the world. Pragmatic evaluation of IEM referrals is essential, particularly pertinent in cases where progression of extra-hepatic disease is anticipated, with long-term outcome expected to be poor. Decision to proceed with liver transplantation is highly individualized based on the child's dynamic risk-benefit profile, their family unit, and their treating multidisciplinary team. Also to be considered is the chance of future treatments, such as gene therapies, emerging in the medium term.

An Analysis of 10,000 Cases of Living Donor Liver Transplantation in Japan: Special Reference to the Graft-Versus-Recipient Weight Ratio and Donor Age.

To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry. The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT. Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed. The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS. Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.

Estimating risk of prolonged mechanical ventilation after liver transplantation in children: PROVE-ALT score.

Children at high risk for prolonged mechanical ventilation (PMV) after liver transplantation (LT) need to be identified early to optimize pulmonary support, allocate resources, and improve surgical outcomes. We aimed to develop and validate a metric that can estimate risk for Prolonged Ventilation After LT (PROVE-ALT). We identified preoperative risk factors for PMV by univariable analysis in a retrospective cohort of pediatric LT recipients between 2011 and 2017 (n = 205; derivation cohort). We created the PROVE-ALT score by mapping multivariable logistic regression coefficients as integers, with cutoff values using the Youden Index. We validated the score by C-statistic in a retrospectively collected separate cohort of pediatric LT recipients between 2018 and 2021 (n = 133, validation cohort). Among total 338 patients, 21% (n = 72) were infants; 49% (n = 167) had cirrhosis; 8% (n = 27) required continuous renal replacement therapy (CRRT); and 32% (n = 111) required management in hospital (MIH) before LT. Incidence of PMV post-LT was 20% (n = 69) and 3% (n = 12) required tracheostomy. Independent risk factors (OR [95% CI]) for PMV were cirrhosis (3.8 [1-14], p = .04); age <1-year (8.2 [2-30], p = .001); need for preoperative CRRT (6.3 [1.2-32], p = .02); and MIH before LT (12.4 [2.1-71], p = .004). PROVE-ALT score ≥8 [Range = 0-21] accurately predicted PMV in the validation cohort with 73% sensitivity and 80% specificity (AUC: 0.81; 95% CI: 0.71-0.91). PROVE-ALT can predict PMV after pediatric LT with a high degree of sensitivity and specificity. Once externally validated in other centers, PROVE-ALT will empower clinicians to plan patient-specific ventilation strategies, provide parental anticipatory guidance, and optimize hospital resources.

Current Endovascular Management of Arterial Complications After Pediatric Liver Transplantation in a Tertiary Center.

Pediatric liver transplant surgery is burdened by arterial complications whose endovascular treatment is not standardized. We report the outcomes of a cohort of pediatric recipients with hepatic artery complications treated by endoluminal procedures. From December 2019 to December 2022, consecutive transplanted pediatric patients who underwent endovascular treatment of hepatic artery complications were reviewed. The analysis included: type of complication (occlusion, stenosis, pseudoaneurysm); onset (acute = < 15days, subacute = 15-90days, late = > 90days); endovascular technique (angioplasty, stenting); complications and outcomes. Technical success was defined as the opacification of the hepatic artery at the final angiogram with < 50% residual stenosis and no pseudoaneurysms. Clinical success was defined by graft's and patient's survival. Seventeen patients (8 males; median age 33months, IQR 9-103) underwent 21 hepatic arteriography procedures for predominantly acute or subacute occlusions (n = 7) or stenosis (n = 11) with concurrent pseudoaneurysms (n = 4). Primary and secondary technical success was achieved in 13/18 and 3/3 procedures, respectively, with overall technical success of 76%. Angioplasty alone was successful in 5/21 procedures; stent-retriever thrombectomy was performed in one occlusion with thrombosis; stenting was required in 9/17 (53%) patients. Clinical success was obtained in 14/17 (82%) patients with hepatic artery patency after a median of 367days (IQR 114.5-500). Clinical failure occurred in 3 permanent occlusions, with 2 deaths and 1 re-transplantation. Procedure-related complications included minor events in 3/17 (18%) patients and 1/17 (6%) death. In liver transplanted children with hepatic artery complications, endovascular treatment may provide clinical success, with stenting often required in acute and subacute conditions. Level 4.

Clinical manifestations and outcomes of coronavirus disease 2019 among pediatric liver transplant recipients in the delta and omicron variant pandemic: A retrospective study.

To determine the clinical manifestations and outcomes of the coronavirus disease 2019 (COVID-19) in children who underwent liver transplantation (LT). A retrospective study was conducted at a transplant center in Thailand to include LT recipients aged < 18 years who had been infected with COVID-19. Out of a total of 54 children, there were 31 probable cases (57.4%) diagnosed using an antigen test kit and 23 confirmed cases (42.6%) diagnosed using polymerase chain reaction (14 children) or severe acute respiratory syndrome coronavirus 2 antigen (9 children). Approximately half of the children (25, 46.3%) received the BNT162b2 vaccine before the infection, with 3 and 2 doses in 5 and 18 children, respectively. While some had COVID-19 during the delta pandemic, most (46 children, 85.2%) were infected during the omicron pandemic, of which manifestations included fever (67.4%), cough (50%), and rhinorrhea (47.8%), and symptoms lasted approximately 3 days. None had severe diseases. All patients with mild-to-moderate disease were advised to continue the same immunosuppressive therapy as before the infection. Compared to unvaccinated children or children with one dose of the vaccine, fever was less common in those who received ≥ 2 doses (OR: 0.08; 95%CI: 0.01-0.57, adjusted for age and immunosuppressive types). Favipiravir was prescribed in most patients (90.7%). Only a few children had long COVID-19 or abnormal liver function tests lasting > 1 month (4 children, 7.4%, both). Pediatric LT recipients with COVID-19 during the delta and omicron variant pandemic reported mild symptoms despite undergoing immunosuppressive therapy.

Safety and Immunogenicity of Live Viral Vaccines in a Multicenter Cohort of Pediatric Transplant Recipients

Live vaccines (measles-mumps-rubella [MMR] and varicella-zoster virus [VZV]) have not been recommended after solid organ transplant due to concern for inciting vaccine strain infection in an immunocompromised host. However, the rates of measles, mumps, and varicella are rising nationally and internationally, leaving susceptible immunocompromised children at risk for life-threating conditions. To determine the safety and immunogenicity of live vaccines in pediatric liver and kidney transplant recipients. This cohort study included select pediatric liver and kidney transplant recipients who had not completed their primary MMR and VZV vaccine series and/or who displayed nonprotective serum antibody levels at enrollment between January 1, 2002, and February 28, 2023. Eligibility for live vaccine was determined by individual US pediatric solid organ transplant center protocols. Exposure was defined as receipt of a posttransplant live vaccine. Transplant recipients received 1 to 3 doses of MMR vaccine and/or 1 to 3 doses of VZV vaccine. Safety data were collected following each vaccination, and antibody levels were obtained at 0 to 3 months and 1 year following vaccination. Comparisons were performed using Mann-Whitney U test, and factors associated with development of postvaccination protective antibodies were explored using univariate analysis. The cohort included 281 children (270 [96%] liver, 9 [3%] kidney, 2 [1%] liver-kidney recipients) from 18 centers. The median time from transplant to enrollment was 6.3 years (IQR, 3.4-11.1 years). The median age at first posttransplant vaccine was 8.9 years (IQR, 4.7-13.8 years). A total of 202 of 275 (73%) children were receiving low-level monotherapy immunosuppression at the time of vaccination. The majority of children developed protective antibodies following vaccination (107 of 149 [72%] varicella, 130 of 152 [86%] measles, 100 of 120 [83%] mumps, and 124 of 125 [99%] rubella). One year post vaccination, the majority of children who initially mounted protective antibodies maintained this protection (34 of 44 [77%] varicella, 45 of 49 [92%] measles, 35 of 42 [83%] mumps, 51 of 54 [94%] rubella). Five children developed clinical varicella, all of which resolved within 1 week. There were no cases of measles or rubella and no episodes of graft rejection within 1 month of vaccination. There was no association between antibody response and immunosuppression level at the time of vaccination. The findings suggest that live vaccinations may be safe and immunogenic after solid organ transplant in select pediatric recipients and can offer protection against circulating measles, mumps, and varicella.