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Abstract Background Psycho-social outcome in children after liver transplantation (LT) is known to be inferior to age-related peers. Yet, when children and their parents are questioned by their nurse or physician about the child’s psycho-social well-being, the answers usually are very positive. We hypothesized that patients and their parents after LT report their psycho-social well-being too enthusiastically when enquired by their personal care takers. Methods Inclusion criteria: LT at the Children’s University Hospital of Geneva 1992–2007, age >3 years, 2 years. Children and their parents were questioned by their well-known, familiar nurse at the annual follow up visit about their personal well-being. To allow for evaluation of answers, scores (good, medium, bad) were attributed to the different questions. 46 children were included in the study. Results Mean age at enquiry was 9.7 years (SD 4 years), mean time after LT was 7.5 years (SD 4.2 years). The different themes were reported as good for: parent–child relationship (83%), relationship with peers (98%), relation with siblings (39%), sport activities (54%), play activities (78%), school performance (87%), expression skills (67%), and general behavior (89%). Conclusion Most of our LT children and their parents consider, during a personal interview with a closely related, familiar nurse, that the child’s psycho-social outcome is good. Yet, it is generally acknowledged that children after LT have negatively altered psycho-social outcomes. Thus, emotionally influenced reports about psycho-social outcome in children after LT must be looked at with care.

Objectives: Optimal nutrition is associated with positive outcomes in critically ill children. In 2017, the Society of Critical Care Medicine (SCCM) and the American Society of Parenteral and Enteral Nutrition (ASPEN) updated guidelines for nutritional support for this population. However, implementation of these guidelines may be delayed due to clinical barriers. We aimed to assess our practice against the recommendations of the ASPEN guidelines, hypothesizing that caregiver bias and clinical factors may hinder their implementation in our pediatric intensive care unit (PICU)., Methods: We focused on two ASPEN recommendations: (1) feeding within 48 h (48H) of admission and (2) meeting two thirds of estimated caloric requirements after seven calendar days. All children aged 1 month to 16 years admitted to our PICU from July 2017 to January 2020 were eligible. Using a retrospective chart review, nutritional and clinical data were collected at the time of admission, at 48H, and 7 calendar days after admission., Results: A total of 533 patients were included. After 48H of admission to the PICU, 402 out of 533 (75.4%) patients received feeding. The following factors were associated with not reaching nutritional goals at 48H: invasive ventilation support, inotropic and vasoactive support, and extracorporeal life support. After 7 days, 95 out of 118 (80.5%) received two thirds of caloric needs. At 7 days, the main obstacle to meeting caloric goals was invasive ventilation., Conclusion: In a representative tertiary PICU, barriers to meeting ASPEN nutritional recommendations included hemodynamic instability or invasive ventilator support, especially within the first 48H of admission., (© 2025 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Liver transplantation (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 nonseroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95% confidence interval [CI], 73%-98%) after a first dose, 95% (95% CI, 85%-99%) after primary vaccination with 1 to 3 doses, comparable to nonimmunocompromized populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with a high seroconversion rate. At their last follow-up (median, 6.1 years; interquartile range, 3.0-8.1 after inclusion), 63% (95% CI, 49%-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Intestinal complications (IC) represent serious adverse events after liver transplantation (LT), however limited research has been conducted in pediatric cohorts. This study aims to describe IC after pediatric LT and to identify associated factors., Methods: Retrospective review of 153 patients having undergone LT, aged 0-18 years, treated in the Swiss Pediatric Liver Center in Geneva. Pre-, per- and postoperative data were analyzed. IC were defined as pathologies or lesions directly associated with LT and attributable to the surgical procedure., Results: 16/153 (11%) patients developed IC: 10/16 mechanical obstructions, 4/16 intestinal perforations and 2/16 sub-mesocolic abscesses. IC patients had a significantly lower Body Mass Index (BMI) (15.5 vs. 16.4, p = 0.019). Children with IC had significantly higher incidence of previous Kasai hepatoportoenterostomy associated with Ladd procedure (13% vs. 2%, p = 0.055), a history of intraoperative iatrogenic intestinal perforation(s) (31% vs. 5%, p = 0.003) and prolonged LT surgery duration (536 vs. 415 min, p = 0.007). Significantly more children with IC had received basiliximab (69% vs. 40%, p = 0.048). Patients with IC exhibited a higher incidence of post-LT sub-occlusions (p < 0.001) and an increased requirement for post-LT parenteral nutrition (p = 0.027). Additionally, IC patients underwent significantly more reoperations (p < 0.001)., Conclusion: One in 10 children post-LT experiences IC, which are associated with significant morbidity. Pre-LT nutritional status appears as an associated factor with IC, along with the necessity for adhesiolysis during LT, often leading to prolonged operative time. These associated factors should alert medical teams to promote early IC diagnosis in patients after LT., (© 2024 The Author(s). Pediatric Transplantation published by Wiley Periodicals LLC.)

Adults and children with cholestatic liver disease are at risk for type C hepatic encephalopathy (HE) and may present lifelong neurocognitive impairment. While the underlying cellular and molecular mechanisms are still incompletely understood, ammonium and bile acids (BAs) seem to play a key role in this pathology, by crossing the blood-brain-barrier and modifying neuronal homeostasis and synaptic plasticity. This experimental study aimed to investigate the effects of ammonium and BAs on dendritic spines of rat hippocampal CA1 neurons. Taking advantage of the bile duct ligated (BDL) in vivo rat model and a hippocampal organotypic rat ex vivo slice model, we analyzed dendritic spine density in both models and spine turnover ex vivo. BDL rats showed decreased dendritic spine densities after 8 weeks, paralleled with increased concentrations of blood ammonium. In organotypic hippocampal slices, exposure to ammonium, tauro-α-muricholic and taurocholic acid induced a decrease in dendritic spine density during the first 3 days, followed by an increase in dendritic spinogenesis during days 4-5, resulting in an increased number of dendritic spines. These observations provide new insights into the effects of ammonium and BAs on dendritic spines and consequently synaptic plasticity in chronic cholestatic liver disease., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Prenatally diagnosed hepatic hilar cysts are a challenging finding for the clinician. They can either be a sign of cystic biliary atresia (BA) or a choledochal cyst (CC), two diagnoses with different postnatal management and prognosis. Based on a case report of four patients, we aim to propose a management algorithm for prenatally diagnosed "hepatic hilar cysts"., Case Presentation: A hepatic hilar cyst, ranging from 5 to 25 mm, was detected prenatally in all four girls confirmed postnatally along with the presence of a gallbladder. Stool color was normal until two weeks of life at which time the stool color became lighter, and the patients developed cholestasis. All were operated before seven weeks of life: Case 1 had a CC with patent but irregular intrahepatic bile ducts at intraoperative cholangiogram, and no communication with the duodenum. A Roux-en-Y bilioenteric anastomosis was performed. The cyst showed complete epithelial lining loss, and liver pathology showed BA features. Case 2 had the final diagnosis of cystic BA with patent but abnormal intrahepatic bile ducts. She underwent two operations: the first operation at four weeks as described for case 1, since intraoperative findings were similar, as was histology. As cholestasis increased postoperatively, she underwent a Kasai hepato-porto-enterostomy six weeks later, where distinct BA findings were found with complete scarring of the hilar plate. Case 3 had a cystic BA with the cyst located within the common bile duct and atretic bile ducts proximal to the porta hepatis. It exhibited no communication with the liver or duodenum. A Kasai operation was performed, with histology showing complete epithelial loss within the cyst wall and scarring of the hilar plate. Case 4 had a cystic BA presenting a completely obliterated hepatic duct with the cyst lying within the common bile duct. A Kasai procedure was performed. Histology showed a common bile duct with a residual lumen of 0.1 mm., Conclusions: The spectrum of disease from CC to BA in the setting of a prenatally discovered hepatic hilar cyst is emphasized. Even if cholangiogram differentiates most patients with BA from those with CC, caution is advised for transitional types., (© 2024. The Author(s).)

Objectives: In 2022, the Biliary Atresia and Related Diseases (BARD) community reached a consensus for the definition of suspected and confirmed cholangitis for biliary atresia (BA) patients after hepatoportoenterostomy (HPE). This study assessed the new standardized BARD definition in a retrospective, multicenter cohort study., Methods: We included BA cases managed between 2010 and 2020 at the Hannover Medical School and Geneva University Hospitals' Swiss Pediatric Liver Center. The standardized BARD cholangitis definition assesses four clinical items and four imaging/laboratory items to define cholangitis. The definition was retrospectively applied to all BA cases having presented, according to their physician, cholangitis within the first year after the HPE. The diagnosis defined by the standardized BARD definition was compared with the final clinical diagnosis made by physicians. The Spearman's correlation coefficient was used to test for correlation between diagnoses made by standardized and clinical appreciation., Results: Of 185 consecutive BA patients, 59 (32%) had at least one episode of cholangitis within the first year after HPE. The correlation between the clinician's impression and the standardized BARD definition was very strong ( r  = 0.8). Confirmed cholangitis definition coincided with the clinician's impression (2.5 [±0.7]/4 clinical items, 2.6 [±0.5]/4 imaging/laboratory items). For suspected cholangitis, the threshold for diagnosis was lower within the standardized BARD definition (1.1 [±0.3]/4 clinical items, 2.2 [±0.8]/4 laboratory/imaging items)., Conclusions: This first retrospective application of the standardized BARD cholangitis definition reveals a very strong correlation with the physician's assessment before standardization. A prospective study is needed to further refine the standardized definition for cholangitis in BA patients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Introduction: Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant., Methods: We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis., Results: A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%)., Conclusion: Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited., (© 2024 S. Karger AG, Basel.)

Background: Chronic hepatic encephalopathy (CHE) has been reported both in patients with congenital porto-systemic shunts (CPSS) and chronic liver disease. CHE is difficult to recognize in children as there is no clear definition and its manifestations are highly variable. CHE is associated with variations in brain volumes and metabolites that have already been demonstrated using 1.5-3T MRI systems. However, the in-depth study of brain metabolism requires the high spectral resolution of high magnetic fields., Objectives and Methods: We analyzed the neurometabolic profile, brain volumes and T 1 relaxation times of a child with a CPSS using high field proton magnetic resonance spectroscopy ( 1 H MRS, 7T) combined with MRI and compared it to an age-matched control group. We also evaluated the impact of shunt closure on neurocognitive symptoms using adapted neuropsychological tests., Results: 7T MRS revealed a significant increase in glutamine compared to controls, a decrease in brain osmolytes, and a slight elevation in NAA concentrations. 7T MRI scans showed morphological abnormalities but no changes in the signal intensity of the globus pallidus. Neurocognitive testing revealed attention deficit disorder, language difficulties, and mild intellectual disability. Most of these areas improved after shunt closure., Conclusions: In this paediatric case of type B HE with normal fasting ammonia, neurometabolic profile was compatible with what has been previously shown in chronic liver disease, while also demonstrating an isolated glutamine peak. In addition, neurocognitive function partially improved after shunt closure, arguing strongly for shunt closure in both presymptomatic and symptomatic patients., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. JPGN Reports published by Wiley Periodicals LLC on behalf of The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: 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., Methods: 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., Results: 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)., Conclusions: 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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Congenital portosystemic shunts are often associated with systemic complications, the most challenging of which are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. In the present paper, we offer expert clinical guidance on the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, and we make recommendations regarding shunt closure and follow-up., Competing Interests: The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2023 The Author(s).)

Background: There is increasing evidence that children or young adults having acquired liver disease in childhood display neurocognitive impairment which may become more apparent as they grow older. The molecular, cellular and morphological underpinnings of this clinical problem are incompletely understood., Aim: Therefore, we used the advantages of highly-resolved proton magnetic resonance spectroscopy at ultra-high magnetic field to analyze the neurometabolic profile and brain morphometry of children with chronic, compensated liver disease, hypothesizing that with high field spectroscopy we would identify early evidence of rising brain glutamine and decreased myoinositol, such as has been described both in animals and humans with more significant liver disease., Methods: Patients (n = 5) and age-matched controls (n = 19) underwent 7T MR scans and short echo time 1 H MR spectra were acquired using the semi-adiabatic SPECIAL sequence in two voxels located in gray and white matter dominated prefrontal cortex, respectively. A 3D MP2RAGE sequence was also acquired for brain volumetry and T 1 mapping. Liver disease had to have developed at least 6 months before entering the study. Subjects underwent routine blood analysis and neurocognitive testing using validated methods within 3 months of MRI and MRS., Results: Five children aged 8-16 years with liver disease acquired in childhood were included. Baseline biological characteristics were similar among patients. There were no statistically significant differences between subjects and controls in brain metabolite levels or brain volumetry. Finally, there were minor neurocognitive fluctuations including attention deficit in one child, but none fell in the statistically significant range., Conclusion: Children with chronic, compensated liver disease did not display an abnormal neurometabolic profile, neurocognitive abnormalities, or signal intensity changes in the globus pallidus. Despite the absence of neurometabolic changes, it is an opportunity to emphasize that it is only by developing the use of 1 H MRS at high field in the clinical arena that we will understand the significance and generalizability of these findings in children with CLD. Healthy children displayed neurometabolic regional differences as previously reported in adult subjects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Chronic liver disease (CLD) is a serious condition where various toxins present in the blood affect the brain leading to type C hepatic encephalopathy (HE). Both adults and children are impacted, while children may display unique vulnerabilities depending on the affected window of brain development.We aimed to use the advantages of high field proton Magnetic Resonance Spectroscopy ( 1 H MRS) to study longitudinally the neurometabolic and behavioural effects of Bile Duct Ligation (animal model of CLD-induced type C HE) on rats at post-natal day 15 (p15) to get closer to neonatal onset liver disease. Furthermore, we compared two sets of animals (p15 and p21-previously published) to evaluate whether the brain responds differently to CLD according to age onset.We showed for the first time that when CLD was acquired at p15, the rats presented the typical signs of CLD, i.e. rise in plasma bilirubin and ammonium, and developed the characteristic brain metabolic changes associated with type C HE (e.g. glutamine increase and osmolytes decrease). When compared to rats that acquired CLD at p21, p15 rats did not show any significant difference in plasma biochemistry, but displayed a delayed increase in brain glutamine and decrease in total-choline. The changes in neurotransmitters were milder than in p21 rats. Moreover, p15 rats showed an earlier increase in brain lactate and a different antioxidant response. These findings offer tentative pointers as to which neurodevelopmental processes may be impacted and raise the question of whether similar changes might exist in humans but are missed owing to 1 H MRS methodological limitations in field strength of clinical magnet., (© 2023. The Author(s).)

Background: Congenital portosystemic shunts (CPSS) are rare vascular malformations associated with the risk of life-threatening systemic conditions, which remain underdiagnosed and often are identified after considerable diagnostic delay. CPSS are characterized by multiple signs and symptoms, often masquerading as other conditions, progressing over time if the shunt remains patent. Which patients will benefit from shunt closure remains to be clarified, as does the timing and method of closure. In addition, the etiology and pathophysiology of CPSS are both unknowns. This rare disorder needs the strength of numbers to answer these questions, which is the purpose of the international registry of CPSS (IRCPSS)., Method: A retrospective and prospective registry was designed using secuTrial® by the ISO certified Clinical Research Unit. Given that a significant number of cases entered in the registry are retrospective, participants have the opportunity to use a semi-structured minimal or complete data set to facilitate data entry. In addition, the design allows subjects to be entered into the IRCPSS according to clinically relevant events. Emphasis is on longitudinal follow-up of signs and symptoms, which is paramount to garner clinically relevant information to eventually orient patient management. The IRCPSS includes also three specific forms to capture essential radiological, surgical, and cardiopulmonary data as many times as relevant, which are completed by the specialists themselves. Finally, connecting the clinical data registry with a safe image repository, using state-of-the-art pseudonymization software, was another major focus of development. Data quality and stewardship is ensured by a steering committee. All centers participating in the IRCPSS have signed a memorandum of understanding and obtained their own ethical approval., Conclusion: Through state-of-the-art management of data and imaging, we have developed a practical, user-friendly, international registry to study CPSS in neonates, children, and adults. Via this multicenter and international effort, we will be ready to answer meaningful and urgent questions regarding the management of patients with CPSS, a condition often ridden with significant diagnostic delay contributing to a severe clinical course., (© 2022. The Author(s).)

Type C hepatic encephalopathy (HE) is a complex neuropsychiatric disorder occurring as a consequence of chronic liver disease. Alterations in energy metabolism have been suggested in type C HE, but in vivo studies on this matter remain sparse and have reported conflicting results. Here, we propose a novel preclinical 18 F-FDG PET methodology to compute quantitative 3D maps of the regional cerebral metabolic rate of glucose (CMR glc ) from a labelling steady-state PET image of the brain and an image-derived input function. This quantitative approach shows its strength when comparing groups of animals with divergent physiology, such as HE animals. PET CMR glc maps were registered to an atlas and the mean CMR glc from the hippocampus and the cerebellum were associated to the corresponding localized 1 H MR spectroscopy acquisitions. This study provides for the first time local and quantitative information on both brain glucose uptake and neurometabolic profile alterations in a rat model of type C HE. A 2-fold lower brain glucose uptake, concomitant with an increase in brain glutamine and a decrease in the main osmolytes, was observed in the hippocampus and in the cerebellum. These novel findings are an important step towards new insights into energy metabolism in the pathophysiology of HE., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

That children present with hepatic encephalopathy (HE) in the setting of acute liver failure (ALF) is accepted and a recognized prognostic factor for survival [1,2]. What is less understood is the impact of chronic liver disease (CLD) on the neuro-cognitive and -psychiatric development and outcomes of children with chronic liver disease early in life. Much is extrapolated from the adult literature or from work in experimental models. But what distinguishes children is that central nervous system development, characterized by massive brain growth, is ongoing at the time of liver disease, arguably exposing them to unique risks, something which cannot be extrapolated from adults. The purpose of this brief review is to summarize what is distinctive about the neurocognition of children with CLD or having presented CLD or portosystemic bypass in childhood., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: In patients with biliary atresia (BA) liver nodules can be identified either by pre-transplant imaging or on the explant. This study aimed to (i) analyze the histopathology of liver nodules, and (ii) to correlate histopathology with pretransplant radiological features. (2) Methods: Retrospective analysis of liver nodules in explants of BA patients transplanted in our center (2000−2021). Correlations with pretransplant radiological characteristics, patient age at liver transplantation (LT), time from Kasai hepatoportoenterostomy (KPE) to LT, age at KPE and draining KPE. (3) Results: Of the 63 BA-patients included in the analysis, 27/63 (43%) had nodules on explants. A majority were benign macroregenerative nodules. Premalignant (low-grade and high-grade dysplastic) and malignant (hepatocellular carcinoma) nodules were identified in 6/63 and 2/63 patients, respectively. On pretransplant imaging, only 13/63 (21%) patients had liver nodules, none meeting radiological criteria for malignancy. The occurrence of liver nodules correlated with patient age at LT (p < 0.001), time KPE-LT (p < 0.001) and draining KPE (p = 0.006). (4) Conclusion: In BA patients, pretransplant imaging did not correlate with the presence of liver nodules in explants. Liver nodules were frequent in explanted livers, whereby 25% of explants harboured malignant/pre-malignant nodules, emphasizing the need for careful surveillance in BA children whose clinical course may require LT.

Introduction: Little is known about bile acid transporter defects on the basolateral side of hepatocytes. In 2015 Vaz et al. published a first case of SLC10A1 mutation causing Na-taurocholate Co-transporting Polypeptide deficiency with hypercholanemia and normal bilirubin and Autotaxin levels. The index patient presented with failure to thrive, but without pruritus or jaundice. Several new cases have been published since, but the full spectrum of clinical presentation of mutations in SLC10A is not known. The primary aim of this review is to report a patient with a novel homozygous mutation and discuss the findings in the light of all other reported cases to date., Material and Methods: We describe the findings of a patient with a previously unreported homozygous mutation and review all published cases to date in English on PubMed., Results: Our female patient born in 2002 presented with a feeding disorder and failure to thrive akin to the first description by Vaz. Workup suggested underlying liver disease although she did not complain of pruritus. Serum levels of aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and bilirubin were normal. Plasma bile acids were chronically elevated, up to 150-fold. A first liver biopsy performed at 2 years of age showed unspecific findings with focal steatosis. Ursodeoxycholic acid treatment was introduced and the liver panel monitored regularly. At age 14, a second biopsy was performed, and histology was within normal limits. At this time, serum Autotaxin levels were found to be in normal range. Finally, genetic analysis revealed a homozygous 5 bp deletion in the gene SLC10A1 resulting in a premature stop codon predicted to lead to a complete NTCP loss of function. Most other reported cases to date carry the c.800C>T (p.Ser267Phe) mutation and are asymptomatic., Discussion: NTCP deficiency appears to have a benign course as most patients are asymptomatic. Many patients seem to present with transient neonatal jaundice. Large variations in total plasma bile acid levels are observed between patients; they may be linked to the underlying genetic mutation or to yet uncharacterized compensatory mechanisms. Longer follow-up is needed to evaluate the long-term consequences of this newly identified inherited disease of bile acid transport., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Patients who have a prolonged stay in the intensive care unit (ICU) are often excluded for organ donation because of supposed deleterious effects of a lengthy ICU stay. We aimed to determine the effects of a prolonged donor stay in the ICU on the outcome of liver transplantation (LT) in children., Methods: Retrospective review of 89 pediatric LT patients, age 0-18 years, period 2003-2018, including patients having undergone whole organ or in situ split LT. The patients were divided into two groups according to the donor length of stay in the ICU. A prolonged stay was defined as >5 days. Recipient, graft, and donor characteristics were compared; outcome parameters included recipient and graft survival rates and postoperative complications., Results: Group short (donor ICU stay <5 days) included 75 patients, group long (donor ICU stay >5 days) 14 patients. Baseline characteristics between recipients did not differ. Donors in group long had significantly more infectious complications and a higher gamma glutamyl transferase (gGT) the day of organ recovery. Incidence of biliary complications post-LT was significantly higher in group long (p = .029). Patient and graft survival rates did not differ significantly between groups., Conclusions: Donors with a prolonged stay in the ICU should still be considered for liver donation if they fulfill most other selection criteria. Recipients from donors having stayed in ICU >5 days may be at increased risk of biliary complications., (© 2021 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Congenital portosystemic shunts (CPSS) are rare vascular anomalies resulting in communications between the portal venous system and the systemic venous circulation, affecting an estimated 30,000 to 50,000 live births. CPSS can present at any age as a multi-system disease of variable severity mimicking both common and rare pediatric conditions., Case Presentations: Case A: A vascular malformation was identified in the liver of a 10-year-old girl with tall stature, advanced somatic maturation, insulin resistance with hyperinsulinemia, hyperandrogenemia and transient hematuria. Work-up also suggested elevated pulmonary pressures. Case B: A young girl with trisomy 8 mosaicism with a history of neonatal hypoglycemia, transient neonatal cholestasis and tall stature presented newly increased aminotransferase levels at 6 years of age. Case C: A 3-year-old boy with speech delay, tall stature and abdominal pain underwent abdominal ultrasound (US) showing multiple liver nodules, diagnosed as liver hemangiomas by hepatic magnetic resonance imaging (MRI). Management and outcome: After identification of a venous malformation on liver Doppler US, all three patients were referred to a specialized liver center for further work-up within 12 to 18 months from diagnosis. Angio-computed tomography (CT) scan confirmed the presence of either an intrahepatic or extrahepatic CPSS with multiples liver nodules. All three had a hyperintense signal in the globus pallidus on T1 weighted cerebral MRI. Right heart catheterization confirmed pulmonary hypertension in cases A and C. Shunts were closed either using an endovascular or surgical approach. Liver nodules were either surgically removed if there was a risk of malignant degeneration or closely monitored by serial imaging when benign., Conclusion: These cases illustrate most of the common chief complaints and manifestations of CPSS. Liver Doppler US is the key to diagnosis. Considering portosystemic shunts in the diagnostic work-up of a patient with unexplained endocrine, liver, gastro-intestinal, cardiovascular, hematological, renal or neurocognitive disorder is important as prompt referral to a specialized center may significantly impact patient outcome.

The role and coexistence of oxidative stress (OS) and inflammation in type C hepatic encephalopathy (C HE) is a subject of intense debate. Under normal conditions the physiological levels of intracellular reactive oxygen species are controlled by the counteracting antioxidant response to maintain redox homeostasis. Our previous in-vivo 1 H-MRS studies revealed the longitudinal impairment of the antioxidant system (ascorbate) in a bile-duct ligation (BDL) rat model of type C HE. Therefore, the aim of this work was to examine the course of central nervous system (CNS) OS and systemic OS, as well as to check for their co-existence with inflammation in the BDL rat model of type C HE. To this end, we implemented a multidisciplinary approach, including ex-vivo and in-vitro electron paramagnetic resonance spectroscopy (EPR) spin-trapping, which was combined with UV-Vis spectroscopy, and histological assessments. We hypothesized that OS and inflammation act synergistically in the pathophysiology of type C HE. Our findings point to an increased CNS- and systemic-OS and inflammation over the course of type C HE progression. In particular, an increase in the CNS OS was observed as early as 2-weeks post-BDL, while the systemic OS became significant at week 6 post-BDL. The CNS EPR measurements were further validated by a substantial accumulation of 8-Oxo-2'-deoxyguanosine (Oxo-8-dG), a marker of oxidative DNA/RNA modifications on immunohistochemistry (IHC). Using IHC, we also detected increased synthesis of antioxidants, glutathione peroxidase 1 (GPX-1) and superoxide dismutases (i.e.Cu/ZnSOD (SOD1) and MnSOD (SOD2)), along with proinflammatory cytokine interleukin-6 (IL-6) in the brains of BDL rats. The presence of systemic inflammation was observed already at 2-weeks post-surgery. Thus, these results suggest that CNS OS is an early event in type C HE rat model, which seems to precede systemic OS. Finally, our results suggest that the increase in CNS OS is due to enhanced formation of intra- and extra-cellular ROS rather than due to reduced antioxidant capacity, and that OS in parallel with inflammation plays a significant role in type C HE., (Copyright © 2021 Swiss Federal Institute of Technology Lausanne. Published by Elsevier Inc. All rights reserved.)

Type C hepatic encephalopathy (HE) is a neuropsychiatric disease caused by chronic liver disease. Management of type C HE remains an important challenge because treatment options are limited. Both the antibiotic rifaximin and probiotics have been reported to reduce the symptoms of HE, but longitudinal studies assessing their effects on brain metabolism are lacking and the molecular mechanisms underpinning their effects are not fully understood. Therefore, we evaluated in detail the effects of these different treatments on the neurometabolic changes associated with type C HE using a multimodal approach including ultra-high field in vivo 1 H MRS. We analyzed longitudinally the effect of rifaximin alone or in combination with the probiotic Vivomixx on the brain metabolic profile in the hippocampus and cerebellum of bile duct ligated (BDL) rats, an established model of type C HE. Overall, while rifaximin alone appeared to induce no significant effect on the neurometabolic profile of BDL rats, its association with the probiotic resulted in more attenuated neurometabolic alterations in BDL rats followed longitudinally (i.e. a smaller increase in Gln and milder decrease in Glu and Cr levels). Given that both rifaximin and some probiotics are used in the treatment of HE, the implications of these findings may be clinically relevant., (© 2021. The Author(s).)

Objectives : T-cell mediated rejection (TCMR) can compromise long-term liver allograft survival. The immunomodulatory properties of vitamin D are increasingly recognized. We investigated whether perturbations in vitamin D metabolism prior to LT may predispose to TCMR in a representative cohort of paediatric LT recipients. Methods : In this retrospective single-center study of children who underwent liver transplantation between 2005 and 2017, we collected serum 25(OH) vitamin D levels and other parameters related to vitamin D metabolism. Post-transplant variables were collected from medical records during the first year following LT. Results : Eighty-two patients were included. Twenty-six (32%) developed TCMR, 52 (65%) presented at least one event of 25(OH) D insufficiency during the year before the transplant, while 23 (32%) had at least one documented elevated plasma parathyroid hormone level. Forty-six patients benefited from nutritional support (56%). The development of TCMR was associated with vitamin D insufficiency pre-LT ( p = 0.01). No significant correlations were identified between PTH levels and incidence of TCMR. The association was stronger in patients transplanted for cholestatic diseases ( p = 0.004). Conclusions : Vitamin D insufficiency before a liver transplant may be associated with TCMR during the first year post-LT. These findings warrant further investigation.

Objectives: The aim of this study was to analyze if contrast-enhanced echocardiography (CEE) is as reliable as lung perfusion scintigraphy (LPS) to detect intrapulmonary shunting (IPS) in children with portal hypertension (PHTN) or congenital/surgical portosystemic shunts (PSS) and to define the number of cardiac cycles required to exclude intrapulmonary shunting., Methods: Inclusion criteria for this cross-sectional study were: (1) presence of PHTN or PSS diagnosed on abdominal ultrasound, (2) technically valid saline contrast echocardiography, (3) lung perfusion scintigraphy within 6 months of CEE. The number of cardiac cycles between right atrial opacification and the arrival of contrast in the left atrium were counted. We analyzed our CEE data at three and five cardiac cycles and compared them with LPS results., Results: The study population was composed of 78 children (38 girls, 49%) ages 2.1-18.8 years (mean 9.8). Sixty-nine patients had PHTN (88%), and nine had a PSS (11%). Eleven subjects (14%) presented evidence of IPS on LPS. Peripheral oxygen saturation was lower in the subjects with IPS detected on LPS (95.3 ± 1.7% vs 99.0 ± 1.4%; P < 0.01). Comparison of LPS with CEE before three and five cardiac cycles showed that CEE is highly specific (95.7%) as early as three cardiac cycles with markedly better sensitivity (72.7%) when using five cardiac cycles. Furthermore, a negative study using five cardiac cycles ruled out IPS with a 95% negative predictive value. The cardiac cycle at which the bubbles appeared in the left atrium was inversely correlated to the shunt index measured using LPS (r = -0.563; P = 0.001)., Conclusion: CEE is sufficient for the screening of IPS in children with PHTN or congenital/surgical PSS, obviating the need for LPS., Competing Interests: The authors have no conflicts of interest to report. No financial support was received for this study. No funds were received from National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); and other(s)., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Brain metabolism evolves rapidly during early post-natal development in the rat. While changes in amino acids, energy metabolites, antioxidants or metabolites involved in phospholipid metabolism have been reported in the early stages, neurometabolic changes during the later post-natal period are less well characterized. Therefore, we aimed to assess the neurometabolic changes in male Wistar rats between post-natal days 29 and 77 (p29-p77) using longitudinal magnetic resonance spectroscopy (MRS) in vivo at 9.4 Tesla. 1 H MRS was performed in the hippocampus between p29 and p77 at 1-week intervals (n = 7) and in the cerebellum between p35 and p77 at 2-week intervals (n = 7) using the SPECIAL sequence at ultra-short echo-time. NOE enhanced and 1 H decoupled 31 P MR spectra were acquired at p35, p48 and p63 (n = 7) in a larger voxel covering cortex, hippocampus and part of the striatum. The hippocampus showed a decrease in taurine concentration and an increase in glutamate (with more pronounced changes until p49), seemingly a continuation of their well-described changes in the early post-natal period. A constant increase in myo-inositol and choline-containing compounds in the hippocampus (in particular glycero-phosphocholine as shown by 31 P MRS) was measured throughout the observation period, probably related to membrane metabolism and myelination. The cerebellum showed only a significant increase in myo-inositol between p35 and p77. In conclusion, this study showed important changes in brain metabolites in both the hippocampus and cerebellum in the later post-natal period (p29/p35-p77) of male rats, something previously unreported. Based on these novel data, changes in some neurometabolites beyond p28-35, conventionally accepted as the cut off for adulthood, should be taken into account in both experimental design and data interpretation in this animal model., (© 2021 International Society for Neurochemistry.)

Portopulmonary hypertension is a rare but serious complication of portal hypertension or portosystemic shunting. Portopulmonary hypertension is an indication for liver transplantation or shunt closure. However, liver transplantation is contraindicated in patients with severe pulmonary arterial hypertension. Reported mortality rates are high in children with portopulmonary hypertension and there are scarce recommendations on its management. Our aim was to report on our real-world experience of managing portopulmonary hypertension in a specialised centre. We describe a series of 6 children with portopulmonary hypertension. Their median age at diagnosis was 13 years (range 10-15). The underlying liver conditions were cirrhosis of unknown origin (1), congenital portocaval shunts (3), biliary atresia (1), and portal vein cavernoma with surgical mesenterico-caval shunt (1). Median mean pulmonary arterial pressure was 47 mmHg (range 32-70), and median pulmonary vascular resistance was 6.6 Wood units (range 4.3-15.4). All patients except one were treated with a combination of pulmonary arterial hypertension-specific therapy (phosphodiesterase type 5 inhibitors and/or endothelin receptor antagonists and/or prostacyclin analogues). Three patients then benefited from shunt closure and the others underwent liver transplantation. Five patients showed improvement or stabilisation of pulmonary arterial hypertension with no deaths after a mean follow-up of 39 months. Based on our limited experience, early and aggressive treatment with a combination of pulmonary arterial hypertension-specific therapy significantly improves patients' haemodynamic profile and enables the performance of liver transplantation and shunt closure with satisfactory outcomes., Competing Interests: Conflict of interest Frédéric Lador reports grants, personal fees and non-financial support from Actelion, personal fees from MSD, grants and personal fees from Bayer, outside the submitted work. Maurice Beghetti has received grants from Actelion and Bayer, contracted as consultant and participate to steering committee for Actelion, Bayer, GSK, Eli Lilly and Acceleron, outside the submitted work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Congenital portosystemic shunts are rare vascular malformations that may have an impact on the heart-lung system. Associated congenital and/or acquired heart diseases are poorly reported., Aims: To analyse cardiovascular disorders within a large congenital portosystemic shunt population, and develop a diagnostic strategy., Methods: Among the 168 consecutive fetuses and children referred for congenital portosystemic shunt (1996-2019), patients presenting with at least one cardiovascular disorder, including congenital heart disease, heart failure, portopulmonary hypertension and/or hepatopulmonary syndrome, were reviewed retrospectively. Cardiovascular disorders were detected using echocardiography and one or more of the following: right-sided heart catheterization; contrast-enhanced transthoracic echocardiography; or lung perfusion radionuclide scan., Results: Overall, 46/168 patients with a congenital portosystemic shunt (27.4%) had one or more clinically significant cardiovascular disorders. Congenital heart disease was present in 28 patients, including six with left heterotaxy. Heart failure was present in six fetuses and 21 neonates (eight without congenital heart disease, and 13 with congenital heart disease). In neonates without congenital heart disease, heart function recovered by the age of 3years. Portopulmonary hypertension was identified in 11 patients (mean age at diagnosis: 9years); it was fatal in one patient, and remained stable in five of six patients after congenital portosystemic shunt closure. In six patients, hepatopulmonary syndrome presented as hypoxia (mean age at diagnosis: 5.3years), which reversed after congenital portosystemic shunt closure., Conclusions: Evaluation and monitoring of the cardiopulmonary status of patients with a congenital portosystemic shunt is mandatory to detect and prevent cardiovascular complications. Furthermore, congenital portosystemic shunts must be sought in patients with unexplained cardiovascular disorders, especially when malformations are present., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Chronic liver disease leads to neuropsychiatric complications called hepatic encephalopathy (HE). Current treatments have some limitations in their efficacy and tolerability, emphasizing the need for alternative therapies. Modulation of gut bacterial flora using probiotics is emerging as a therapeutic alternative. However, knowledge about how probiotics influence brain metabolite changes during HE is missing. In the present study, we combined the advantages of ultra-high field in vivo 1 H MRS with behavioural tests to analyse whether a long-term treatment with a multistrain probiotic mixture (VIVOMIXX) in a rat model of type C HE had a positive effect on behaviour and neurometabolic changes. We showed that the prophylactic administration of this probiotic formulation led to an increase in gut Bifidobacteria and attenuated changes in locomotor activity and neurometabolic profile in a rat model of type C HE. Both the performance in behavioural tests and the neurometabolic profile of BDL + probiotic rats were improved compared to the BDL group at week 8 post-BDL. They displayed a significantly lesser increase in brain Gln, a milder decrease in brain mIns and a smaller decrease in neurotransmitter Glu than untreated animals. The clinical implications of these findings are potentially far-reaching given that probiotics are generally safe and well-tolerated by patients.

Aims and Background: Ophthalmic abnormalities are amongst the 5 major criteria required for a diagnosis of Alagille syndrome (ALGS), of which embryotoxon, pseudopapilledema, and hypopigmented retinopathy are the most common. Papilledema with or without intracranial hypertension (ICHT) is rarely described. We report 9 pediatric cases of ALGS with bilateral papilledema, 5 of which were diagnosed with ICHT., Methods: The ophthalmic data from 85 patients with clinically and/or genetically (n = 37) proven ALGS were reviewed. The study inclusion criteria were a positive diagnosis of ALGS and availability of ophthalmic follow-up data. Ophthalmic data from 40 patients after liver transplantation (LT) for other indications were also analyzed., Results: Nine (13.0%) of the 69 patients meeting the inclusion criteria had papilledema. The neurological and neuroimaging results in all 9 patients were normal. These 9 patients were categorized into 4 groups: a nontransplant group (n = 1), a group with pretransplant papilledema persistent after LT (n = 2), a group with papilledema occurring after LT with spontaneous resolution (n = 1), and a group with papilledema and signs of ICHT after LT (n = 5). The patients with ICHT were treated with steroids alone (n = 1) or with acetazolamide (n = 4). A ventriculoperitoneal shunt was placed in 2 of the 5 cases because of progressive visual loss. Pseudopapilledema was present in 10 additional patients (14.5%, 10/69). One (2.5%) of the 40 patients without ALGS developed papilledema after LT., Conclusions: True ICHT may be underdiagnosed in patients with ALGS. Our findings underscore the need for close ophthalmic follow-up before and after LT in these patients.

Background: The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype., Methods: PB were performed at least 1 year after transplantation. We identified 4 phenotypes: normal, fibrosis, inflammation, inflammation with fibrosis. Cell types were counted after immunostaining for CD3, CD4, CD8, CD68, CD20, MUM1, and FoxP3., Results: Forty-four patients underwent 1 PB between 2000 and 2015. Eleven percent (5/44) of PB displayed normal histology, 13.6% (6/44) fibrosis, 34.1% (15/44) inflammation, and 40.9% (18/44) inflammation and fibrosis. The main cell types in the portal tracts and lobules were CD3+ and CD68+ cells. Frequency of de novo DSA was 63% (27/44). The presence of CD8+ cells in the lobules was associated with fibrosis. Inflammation and fibrosis in PB were associated with the presence of circulating de novo DSA, number of de novo DSA, and C1q binding activity when compared to other phenotypes., Conclusions: T cells (CD3+) and macrophages (CD68+) were the most prevalent cell-types in PB. In the presence of inflammation, portal tracts were enriched in CD3+, CD20+ but displayed fewer CD68+. This coincided with the presence and number of de novo DSA. How these cellular and humoral actors interact is unclear, but peripheral DSA may be a marker of immune cellular activity in the seemingly quiescent allograft.

Introduction:  Hepatoportoenterostomy (HPE) is the first-line treatment for biliary atresia (BA) patients. This study aims to describe perioperative complications after HPE and to analyze their impact on outcome., Materials and Methods:  Patients with HPE (Swiss National Biliary Atresia Registry, 1994-2017) were retrospectively analyzed. Perioperative complications were defined as complications occurring up to 30 days after surgery. Surgical complications were defined as directly related to the surgical act; medical complications were defined as any other deviation from the uneventful postoperative course., Results:  Sixty-two patients were included. Median age at HPE was 63 days (18-126). Twenty six patients out of 62 (42%) had ≥ 1 complications: 6/62 (10%) surgical, 24/62 (39%) medical, that is, we observed 7 surgical and 28 medical complications. As for medical complications, cholangitis was the most frequent: 19/28 (68%). Lower gestational age at birth correlated with more overall complications ( p  = 0.02). Age, weight at HPE, syndromic BA, and postoperative steroid administration were not significantly correlated. There were no perioperative deaths. Perioperative complications did not correlate with overall survival ( p  = 0.14) and survival with native liver ( p  = 0.55)., Conclusion:  HPE is often associated with perioperative medical complications. Lower gestational age at birth was significantly associated with more complications. Perioperative complications had no impact on overall outcome., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Type C hepatic encephalopathy (type C HE) is increasingly suspected in children with chronic liver disease (CLD), and believed to underlie long-term neurocognitive difficulties. The molecular underpinnings of type C HE in both adults and children are incompletely understood. In the present study we combined the experimental advantages of in vivo high field 1 H magnetic resonance spectroscopy with immunohistochemistry to follow longitudinally over 8 weeks the neurometabolic changes in the hippocampus of animals having undergone bile duct ligation as pups. Rats who develop CLD early in life displayed pronounced neurometabolic changes in the hippocampus characterized by a progressive increase in glutamine concentration which correlated with plasma ammonia levels and a rapid decrease in brain myo-inositol. Other neurometabolic findings included a decrease in other organic osmolytes (taurine, choline-containing compounds and creatine), ascorbate and glutamate. At the cellular level, we observed an increase in glial fibrillary acidic protein (GFAP) and aquaporin 4 (AQP4) expression in the hippocampus at 4 weeks post bile duct ligation (BDL), together with astrocytic morphological alterations. These findings differ from observations in the brain of adult rats following BDL, and are in keeping with the commonly accepted theory of age-dependent vulnerability.

Despite growing interest about the impact of donor-specific HLA antibodies (DSA) in LT limited data are available for pediatric recipients. Our aim was to perform a retrospective single-center chart review of children (0-16 years) having undergone LT between January 1, 2005 and December 31, 2017, to characterize DSA, to identify factors associated with the development of de novo DSA, and to analyze potential associations with the diagnosis of TCMR. Information on patient- and donor-characteristics and LB reports were analyzed retrospectively. Serum obtained before LT and at LB was analyzed for presence of recipient HLA antibody using Luminex ® technology. MFI > 1000 was considered positive. In 63 pediatric LT recipients with a median follow-up of 72 months, the overall prevalence of de novo DSA was 60.3%. Most were directed against class II antigens (33/38, 86.8%). Preformed DSA were present in 30% of patients. Twenty-eight (28/63) patients (44.4%) presented at least one episode of TCMR, mostly (12/28, 43%) moderate (Banff 6-7). De novo DSA were significantly more frequent in patients with TCMR than in patients without (75% vs 48.6%, P = .03), and patients with preformed and de novo DSA had a significantly higher rate of TCMR than patients without any DSA (66.7% vs 20%, P = .02). Neither preformed DSA nor de novo DSA were associated with frequency or severity of TCMR. Recipients with lower weight at LT developed de novo DSA more frequently (P = .04). De novo DSA were highly prevalent in pediatric LT recipients. Although associated with the development of TCMR, they did not appear to impact the frequency or severity of TCMR or graft survival. Instead, de novo DSA may suggest a state of insufficient IS., (© 2019 Wiley Periodicals, Inc.)

Background: Immunosuppressive therapy must be guided by therapeutic drug monitoring (TDM) in paediatric liver (LT) and kidney transplantation (KT) patients to prevent under- and overdosing, which have clinical consequences., Aim: The purpose of our study was to analyse TDM results in our institutions and evaluate factors associated with blood level stabilisation after LT and KT., Methods: Blood levels of immunosuppressants were measured by immunoassay analysis. We compared blood level stabilisation between LT and KT, and evaluated associated factors in a retrospective study in two Swiss university hospitals., Results: Forty-six patients (27 LT [median age 1.0 y], 19 KT [15.1 y]) were included. During the first month after transplantation, 32.8% (LT) and 41.2% (KT) of tacrolimus, and 22.1% (KT) of ciclosporin trough levels (measured before the next dose) were within target. In KT, trough levels stabilised earlier for tacrolimus than for ciclosporin (p = 0.02). Intensive care and hospital discharge occurred earlier in KT patients (p &lt;0.001). Living-donor LT was associated with an earlier intensive care discharge compared with deceased donor (5.5 vs 11 days, p = 0.02). Primary metabolic disease and graft/recipient weight-ratio &ge;0.03 was associated with earlier tacrolimus level stabilisation (14 vs 18 days, p = 0.01 and 15 vs 22 days, p = 0.05, respectively). In KT, recipient age (&ge;15.1 years) and weight (&ge;39.4 kg) were associated with an earlier trough level stabilisation (both 13 days vs not reached, p &lt;0.001), and age with earlier hospital discharge (10 vs 14 days, p = 0.02)., Conclusion: Immunosuppressant trough levels were often outside the target range in the first month after LT and KT. Organ-specific factors were associated with trough stabilisation.