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Background: Biliary complications are common in pediatric liver transplant. Strictures resistant to interventional radiology procedures can be extremely challenging to manage and may result in the need of surgery or retransplantation. Methods: This case report illustrates the use of biodegradable stents post left lateral segment live donor liver transplant in a pediatric patient with a recalcitrant chronic stricture of the biliary‐enteric anastomosis. The patient developed a high stricture requiring multiple interventions and eventual access of both the segment II and segment III ducts of the graft. Results: To ensure adequate biliary drainage, two biodegradable stents were deployed using a "kissing‐stent" technique. The stents were successfully deployed and allowed the patient to remain free from an internal–external biliary drain for 11 months, with eventual redeployment of an additional biodegradable stent. Conclusion: In patients with recalcitrant stenosis of the biliary anastomosis, biodegradable stents may provide durable drainage, optimizing graft function and delaying retransplantation in addition to keeping patients without external devices, thus improving quality of life. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation is the life‐saving treatment for many end‐stage pediatric liver diseases. The perioperative course, including surgical and anesthetic factors, have an important influence on the trajectory of this high‐risk population. Given the complexity and variability of the immediate postoperative course, there would be utility in identifying risk factors that allow prediction of adverse outcomes and intensive care unit trajectories. Aims: The aim of this study was to develop and validate a risk prediction model of prolonged intensive care unit length of stay in the pediatric liver transplant population. Methods: This is a retrospective analysis of consecutive pediatric isolated liver transplant recipients at a single institution between April 1, 2013 and April 30, 2020. All patients under the age of 18 years receiving a liver transplant were included in the study (n = 186). The primary outcome was intensive care unit length of stay greater than 7 days. Results: Recipient and donor characteristics were used to develop a multivariable logistic regression model. A total of 186 patients were included in the study. Using multivariable logistic regression, we found that age < 12 months (odds ratio 4.02, 95% confidence interval 1.20–13.51, p =.024), metabolic or cholestatic disease (odds ratio 2.66, 95% confidence interval 1.01–7.07, p =.049), 30‐day pretransplant hospital admission (odds ratio 8.59, 95% confidence interval 2.27–32.54, p =.002), intraoperative red blood cells transfusion >40 mL/kg (odds ratio 3.32, 95% confidence interval 1.12–9.81, p =.030), posttransplant return to the operating room (odds ratio 11.45, 95% confidence interval 3.04–43.16, p =.004), and major postoperative respiratory event (odds ratio 32.14, 95% confidence interval 3.00–343.90, p <.001) were associated with prolonged intensive care unit length of stay. The model demonstrates a good discriminative ability with an area under the receiver operative curve of 0.888 (95% confidence interval, 0.824–0.951). Conclusions: We develop and validate a model to predict prolonged intensive care unit length of stay in pediatric liver transplant patients using risk factors from all phases of the perioperative period. [ABSTRACT FROM AUTHOR]

Background: Shortages of liver allografts for children awaiting transplantation have led to high LT waitlist mortality. Prior studies have shown that usage of TVG can reduce waiting time and waitlist mortality, but their use is not universal. We sought to compare patient and graft survival between WLG and TVG and to identify potential associated risk factors in a contemporary pediatric LT cohort. Methods: We performed a retrospective analysis of patient survival, graft survival, and biliary and vascular complications for LT recipients <18 years old entered into the Society of Pediatric Liver Transplantation prospective multicenter database. Results: Of 1839 LT recipients, 1029 received a WLG and 810 received a TVG from either a LD or a DD. There was no difference in patient survival or graft survival by graft type. Three‐year patient survival and graft survival were 96%, 93%, and 96%, and 95%, 89%, and 92% for TVG‐LD, TVG‐DD, and WLG, respectively. Biliary complications were more frequent in TVG. Hepatic artery thrombosis was more frequent in WLG. Multivariate analysis revealed primary diagnosis was the only significant predictor of patient survival. Predictors for graft survival included time‐dependent development of biliary and vascular complications. Conclusions: There were no significant differences in patient and graft survival based on graft types in this North American multi‐center pediatric cohort. Widespread routine use of TVG should be strongly encouraged to decrease mortality on the waitlist for pediatric LT candidates. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) is one of the causes of conjugated hyperbilirubinemia in infants which if untreated leads to end-stage liver disease and death. Percutaneous Trans-hepatic Cholecysto-Cholangiography (PTCC) is a minimally invasive study which can be utilized in the diagnostic work-up of these patients. This study's purpose is to describe the experience with PTCC in neonates, the imaging findings encountered, and the abnormal patterns which warrant further investigation. Methods: A 16-year single-center retrospective study of patients with persistent neonatal cholestasis (suspected BA) undergoing PTCC. Patient demographics, laboratory values, PTCC images, pathology and surgical reports were reviewed. Results: 73 patients underwent PTCC (68% male, mean age 8.7 weeks, mean weight 4.0 Kg). The majority of studies were normal (55%). Abnormal patterns were identified in 33 cases, 79% were diagnosed with BA and 12% with Alagille syndrome. Non-opacification of the common hepatic duct with a narrowed common bile duct (42%) and isolated small gallbladder (38%) were the most common patterns in BA. Conclusion: PTCC is a minimally invasive study in the diagnostic work-up of infants presenting with conjugated hyperbilirubinemia (suspected BA). Further invasive investigations or surgery can be avoided when results are normal. [ABSTRACT FROM AUTHOR]

Pediatric acute liver failure (PALF) is a life-threatening disorder characterized by acute hepatocellular injury occurring in children without recognized underlying liver disease. The clinicopathologic evaluation of PALF requires a different approach from that in adults. The diagnostic considerations differ depending on the age, personal and family history, geographical region, and clinical presentation. Distinct entities such as gestational alloimmune liver disease, herpes simplex virus infection, and metabolic disorders should be considered in neonates with acute liver failure, while acetaminophen toxicity and autoimmune hepatitis are more frequently seen in older children and adolescents. An identified cause for PALF despite a negative complete evaluation (indeterminate) is lacking in 30 to 50% of cases. Although not routinely performed in the setting of PALF, liver biopsy may be helpful in assessing the etiology, potential mechanisms of injury, determining the appropriateness of liver transplantation, and prognostication of the patients. In this article, we review the clinicopathologic characteristics of PALF with an emphasis on general approach of pathologic evaluation and histopathologic characteristic of selected entities. [ABSTRACT FROM AUTHOR]

Background: Motor skill acquisition plays an important role in physical activity participation and overall social and physical health. Limited studies have examined motor development in children pre‐and post‐liver transplant (LT). Methods: Retrospective review of motor outcomes in children <6 years old with cholestatic liver disease assessed pre‐and 1‐year post‐isolated LT. Measures include Alberta Infant Motor Scale and Peabody Developmental Motor Scales (gross motor quotient (GMQ), fine motor quotient (FMQ), and total motor quotient (TMQ)). Association of medical variables with motor outcomes was explored. Results: Participants included 33 (58% male) children with diagnoses of biliary atresia (70%), Alagille syndrome (21%), and others (9%). Median age at LT was 10 (IQR 7.0–20.5) months. Pre‐LT >75% of children were at risk for motor delay (≤10th percentile on AIMS/ ≥1SD below mean GMQ). Post‐LT, 52% scored ≥1 SD below the mean GMQ compared with 22% FMQ. Children at risk/delayed pre‐LT had an increased risk of motor delay on GMQ post‐LT (odds ratio 11.43, 95% CI 1.12–116.7, p =.017). Higher INR pre‐LT correlated with lower TMQ post‐LT (r = −.51, p =.003). Longer waitlist time correlated with lower FMQ post‐LT (r =.41, p =.03). GMQ post‐LT and height z‐scores pre‐LT (r =.46, p =.02) and post‐LT (r =.45, p <.01) were positively correlated. There was no correlation with presence of ascites, weight z‐score, length of hospitalization, and age at LT. Conclusions: Young children have increased risk of motor delay pre‐LT, which may persist post‐LT. Severity of liver disease and growth delays may impact motor development, highlighting the need for ongoing rehabilitation pre‐ and post‐LT. [ABSTRACT FROM AUTHOR]

Background: HRQOL is a key outcome following pediatric LT. Parent‐proxy reports may substitute for patients unable to report their own HRQOL. This study compared parent‐proxy and self‐reported HRQOL in children who have undergone LT. Methods: Pediatric LT recipients between the ages of 8 and 18 years, and a parent, completed self and proxy versions of the PeLTQL questionnaire, PedsQL Generic and Transplant modules, and standardized measures of depression and anxiety. Results: Data from 129 parent–patient dyads were included. Median parent age was 44 years, and most (89%) were mothers. Median patient age was 2.5 years at LT and 13.6 years at the time of study participation. Parents had significantly lower scores than patients on PedsQL total generic (70.8 ± 18.5 and 74.3 ± 19.0, p =.01), PeLTQL coping and adjustment (63.0 ± 15.6 and 67.3 ± 16.2, p <.01), and social‐emotional (66.3 ± 14.9 and 71.9 ± 15.6, p <.001) domains. Higher patient anxiety and depression were related to larger absolute differences between parent‐proxy and self‐reported scores on all HRQOL measures (all p <.05). In this disparity, parents reported higher HRQOL scores than their child as self‐reported anxiety and depression scores increased. Conclusions: Differences in concordance between parent‐proxy and self‐reported HRQOL scores can be more prominent when children have more symptoms of anxiety and depression. Children's mental health symptoms should be queried, if feasible, when interpreting differences in parent and child reports of HRQOL. [ABSTRACT FROM AUTHOR]

Approximately 50% of infants with biliary atresia (BA) undergoing Kasai portoenterostomy show survival with native liver (SNL) at age 2 years. Predictors of disease progression after age 2 years are unknown, despite estimates of 20%‐30% undergoing liver transplant (LT) between age 2 and 18 years. We sought to address this knowledge gap by developing prognostic models in participants of the multicenter prospective National Institutes of Health‐supported Childhood Liver Disease Research Network. We extracted 14 clinical and biochemical variables at age 2 years to develop two models for future outcomes: 1) LT or death (LTD) and 2) first sentinel event (SE), either new onset ascites, hepatopulmonary syndrome (HPS), or gastrointestinal (GI) bleed. A total of 240 participants, enrolled between 2004 and 2017, were followed until a median age of 5.1 years (range, 2.0‐13.3 years). Of these participants, 38 underwent LT (n = 37) or death (n = 1); cumulative incidence, 23.7% (95% confidence interval [CI], 16.2%‐32.0%). Twenty‐seven experienced either new‐onset ascites (n = 13), HPS (n = 1), or GI bleed (n = 14). One participant had ascites and GI bleed concurrently; cumulative incidence, 21.5% (95% CI, 14.2%‐29.8%) by age 10 years. The Cox proportional hazard model predicted risk of LTD, using total bilirubin, albumin, platelet count, and history of either ascites or cholangitis (BA LTD model), with a C‐index of 0.88 (range, 0.86‐0.89). A cause‐specific hazard competing risk model predicted SE using platelet count and gamma glutamyltransferase levels (BA SE model) with a C‐index of 0.81 (range, 0.80‐0.84). Internal model validity was assessed using Harrell's C‐index with cross‐validation. Conclusion: Stratification using these models identified risk of poor outcomes in patients with BA SNL after age 2 years. The models may identify those who would benefit from enhanced clinical surveillance and prioritization in clinical trials. [ABSTRACT FROM AUTHOR]

This case report describes a 13‐year 10‐month‐old girl who underwent a deceased‐donor split LT for primary diagnosis of biliary atresia at the age of 12 months, who presented with a lower GI bleed. Ultrasound and CT revealed a venous vascular anomaly involving the cecum and ascending colon, with communication of the SMV and pelvic veins consistent with a CEPS. Associated varices were noted in the pelvis along the uterus and urinary bladder. These findings were confirmed by trans‐hepatic porto‐venography, which was diagnostic and therapeutic as a successful embolization of the CEPS was performed using micro‐coils. There were no complications following the procedure and no further GI bleeding occurred, illustrating the efficacy of this treatment option for CEPS. We discuss the literature regarding the presenting complaint of GI bleeding post–LT, CEPS as a rare cause of GI bleeding and its association with PV, and the classification and treatment of CEPS. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, the unintentional loss of skeletal muscle mass, is associated with poor outcomes in adult patient populations. In adults, sarcopenia is often ascertained by cross‐sectional imaging of the psoas muscle area (PMA). Although children with chronic medical illnesses may be at increased risk for muscle loss because of nutritional deficiencies, physical deconditioning, endocrine anomalies, and systemic inflammation, consistent quantitative definitions for sarcopenia in children are lacking. We aimed to generate paediatric reference values for PMA at two intervertebral lumbar levels, L3–4 and L4–5. Methods: In this cross‐sectional study, we analysed abdominal computed tomography scans of consecutive children presenting to the emergency department. Participants were children 1–16 years who required abdominal cross‐sectional imaging after paediatric trauma between January 1, 2005 and December 31, 2015 in a large Canadian quaternary care centre. Children with a documented chronic medical illness or an acute spinal trauma at presentation were excluded. Total PMA (tPMA) at levels L3–4 and L4–5 were measured in square millimetres (mm2) as the sum of left and right PMA. Age‐specific and sex‐specific tPMA percentile curves were modelled using quantile regression. Results: Computed tomography images from 779 children were included. Values of tPMA at L4–5 were significantly larger than at L3–4 at all ages, but their correlation was high for both girls (r = 0.95) and boys (r = 0.98). Amongst girls, tPMA 50th percentile values ranged from 365 to 2336 mm2 at L3–4 and from 447 to 2704 mm2 for L4–5. Amongst boys, 50th percentile values for tPMA ranged between 394 and 3050 mm2 at L3–4 and from 498 to 3513 mm2 at L4–5. Intraclass correlation coefficients were excellent at L3–4 (0.97, 95% CI 0.94 to 0.981) and L4–5 (0.99, 95% CI 0.986 to 0.995). Weight and tPMA were correlated, stratified by sex for boys (L3–4 r = 0.90; L4–5 r = 0.90) and for girls (L3–4 r = 0.87; L4–5 r = 0.87). An online application was subsequently developed to easily calculate age‐specific and sex‐specific z‐scores and percentiles. Conclusions: We provide novel paediatric age‐specific and sex‐specific growth curves for tPMA at intervertebral L3–4 and L4–5 levels for children between the ages of 1‐16 years. Together with an online tool (https://ahrc‐apps.shinyapps.io/sarcopenia/), these tPMA curves should serve as a reference enabling earlier identification and targeted intervention of sarcopenia in children with chronic medical conditions. [ABSTRACT FROM AUTHOR]

Biliary atresia is a progressive fibroinflammatory cholangiopathy of infancy that is associated with activation of innate and adaptive immune responses targeting bile ducts. A recently completed multicenter phase I/IIA trial of intravenous immunoglobulin in biliary atresia did not improve serum total bilirubin levels at 90 days after hepatoportoenterostomy or survival with the native liver at 1 year. A mechanistic aim of this trial was to determine if the peripheral blood immunophenotype was associated with clinical outcomes. Flow cytometry of peripheral blood cell markers (natural killer [NK], macrophage subsets, T‐ and B‐cell subsets, regulatory T cells), neutrophils, and activation markers (clusters of differentiation [CD]38, CD69, CD86, human leukocyte antigen‐DR isotype [HLA‐DR]) was performed on 29 patients with biliary atresia at baseline and at 60, 90, 180, and 360 days after hepatoportoenterostomy. Plasma cytokines and neutrophil products were also measured. Spearman correlations of change of an immune marker from baseline to day 90 with change in serum bilirubin revealed that an increase in total bilirubin correlated with 1) increased percentage of HLA‐DR+CD38+ NK cells and expression of NK cell activation markers CD69 and HLA‐DR, 2) decreased percentage of regulatory T cells, and 3) increased interleukin (IL)‐8 and associated neutrophil products (elastase and neutrophil extracellular traps). Cox modeling revealed that the change from baseline to day 60 of the percentage of HLA‐DR+CD38+ NK cells and plasma IL‐8 levels was associated with an increased risk of transplant or death by day 360. Conclusion: Poor outcomes in biliary atresia correlated with higher peripheral blood NK cells and IL‐8 and lower regulatory T cells. Future studies should include immunotherapies targeting these pathways in order to protect the biliary tree from ongoing damage. [ABSTRACT FROM AUTHOR]

The long-term course and outcome of DAIH is unknown. A retrospective multicenter study assessing associations and long-term consequences of DAIH developing in a transplanted allograft is presented. Children with DAIH were followed from diagnosis until death, re- LT, or transfer of care and for a minimum of 1 year. A total of 31 patients of 1833 (1.7%) LT were identified; 29 followed for a median of 7.1 years (range, 1.6-15); 52% had no rejection preceding diagnosis of DAIH. Transaminases fell following treatment with steroids and antimetabolites ( ALT 108 vs 39 U/L ( P=.002); AST 112 vs 52 U/L ( P=.003); GGT 72 vs 36 U/L ( P=.03), but this was not universally sustained. Transaminases >2X ULN observed in 38% of patients at last follow-up; commonly GGT, attributed to bile duct injury and ductopenia. Portal hypertension ( PHT) was seen in four patients and associated with severe fibrosis and cirrhosis. Re- LT occurred in two patients for chronic rejection ( CR) and uncontrolled PHT with gastrointestinal bleeding, respectively. No deaths from DAIH were reported. DAIH is an uncommon complication following pediatric LT requiring prolonged and augmented immunosuppression. It is associated with continued allograft dysfunction and may lead to bile duct injury, CR, and PHT necessitating re- LT. [ABSTRACT FROM AUTHOR]

LT in neonates and young infants can be challenging due to a variety of factors. To describe the waitlist mortality rates and outcomes of patients listed and transplanted as infants identified from the UNOS database. Infants listed for LT between January 1985 and September 2010 were identified from the UNOS database. Mortality on the waitlist as well as outcomes post- LT was compared between infants aged ≤60 days (Group 1), 61-179 days (Group 2), and 180-364 days (Group 3). Of 6763 infants listed for LT (Group 1 n = 496, Group 2 n = 2404, Group 3 n = 3863), mean age at listing was 196 ± 87 days (Group 1, 29 ± 16 days; Group 2, 132 ± 32 days; Group 3, 257 ± 52 days). Waitlist mortality was highest in Group 1 (Group 1 vs. 3 HR 3.01, 95% CI 2.19-4.15, Group 2 vs. Group 3 HR 0.82, 95% CI 0.66-1.03). One- and five-yr graft survival was 59.6% and 42% (Group 1), 66% and 45% (Group 2), and 66.8% and 41% (Group 3) (one-yr survival p = 0.20; five-yr survival p = 0.19). Infants listed for LT at age ≤60 days had greater waitlist mortality risk than older infants. Infants undergoing LT at age ≤60 days had similar rates of patient and graft survival to older infants. [ABSTRACT FROM AUTHOR]

CV disease is a major cause of morbidity and mortality following solid organ transplantation in adults. While the prevalence of multiple cardiometabolic risk factors is increased in pediatric solid organ transplant recipients, it is not clear whether they have subclinical CV changes. c IMT, central p WV, and CAC are indicative of subclinical CV disease, and, in adults, predict future CV events. The objective of this systematic review and meta-analysis was to investigate the prevalence of subclinical CV changes, as measured by c IMT, p WV, and CAC among pediatric solid organ transplant recipients. We searched MEDLINE® and EMBASE and conducted meta-analysis for studies that evaluated c IMT, central p WV, and CAC among pediatric solid organ transplant recipients (kidney, lung, intestine and liver). The search identified nine eligible studies that included a total of 259 patients and 685 healthy controls. Eight studies reported on kidney transplant recipients and one study on a combined cohort of kidney and liver transplant recipients. The mean c IMT of transplant recipients was significantly higher than that of healthy controls (mean difference = 0.05 mm, 95% CI 0.02-0.07; p < 0.0001) with an estimated pooled prevalence of elevated c IMT of 56.0% (95% CI 17.0-95.0). The one study that assessed p WV showed increased vascular stiffness in transplant recipients compared to healthy controls. No studies assessing for CAC were found. There were limited data regarding subclinical CV disease following pediatric solid organ transplantation. In conclusion, kidney transplantation in childhood is associated with a higher prevalence of subclinical CV changes compared to healthy children. Longitudinal studies are needed to determine whether children have increased CV morbidity and mortality after transplantation. [ABSTRACT FROM AUTHOR]