An innocent bystander or a predisposing culprit? Kidney injury following pediatric liver transplantation.

BACKGROUND: Survival after pediatric liver transplantation has increased dramatically over the years, revealing extra-hepatic complications including impaired kidney function. We conducted a large single-center retrospective study to evaluate kidney outcomes after pediatric liver transplantation. METHODS: From electronic charts of 121 children who underwent liver transplantation during 2007-2020, we collected pre- and post-transplant data. We investigated the presence of post-transplant permanent kidney injury, including proteinuria, hypertension, and decreased estimated glomerular filtration rate (eGFR). We excluded children who died, underwent liver-kidney transplantation, or had less than 1 year of follow-up. RESULTS: During a median follow-up of 5.1 (interquartile range 2.9-7.3) years, eGFR decreased, mostly in the first year post-transplant. In addition, 41% of the children presented with acute kidney injury. At their last follow-up, 35% showed permanent kidney injury (hypertension 13%, proteinuria 36%, and eGFR < 90 mL/min per 1.73 m2 7%). Kidney ultrasounds were abnormal for 44% of the children at the last visit, compared to 11% before transplant (p < 0.001). In multivariate analysis, abnormal kidney ultrasound before transplant (odds ratio = 4.53, 95% CI 1.1-18.7) and liver disease with potential risk of primary kidney involvement (odds ratio = 4.77, 95% CI 1.58-14.4) were predictors for hypertension or decreased eGFR at the last follow-up. CONCLUSIONS: The high prevalence of kidney injury after pediatric liver transplantation and the pretransplant predictors for kidney injury highlight the importance of a thorough kidney pretransplant evaluation and follow-up.

Biliary strictures post pediatric liver transplantation-incidence and risk factors in a single tertiary referral transplant center.

BACKGROUND: Biliary strictures are a significant cause of morbidity and graft loss in pediatric liver transplant recipients. Risk factors for the development of biliary strictures are not fully established. We aimed to evaluate the incidence of biliary strictures and treatment modalities outcomes and to identify potential risk factors for occurrence. METHODS: Pediatric patients who underwent liver transplantation in the single tertiary pediatric liver transplant center in Israel were evaluated. We compared demographics, presentation, laboratory results, imaging, treatment, and outcomes between patients with and without biliary stricture. Multivariate regression analyses were used to identify risk factors for biliary strictures. RESULTS: Among 121 pediatric liver transplant patients, 65 (53.7%) were males; the median age at the time of liver transplantation was 43 (3-215) months. Fifteen patients (12.4%) had biliary strictures following transplantation. One (7%) patient with biliary stricture was treated via endoscopic retrograde cholangiopancreatography, and 12 patients (80%) underwent interventions via a percutaneous transhepatic approach. Nine of the 12 patients were treated successfully, requiring one or multiple procedures, while the remaining had surgery or laser therapy. Risk factors for the development of biliary strictures were biliary leak, acute cellular rejection, and the presence of two biliary anastomoses. CONCLUSIONS: In our cohort, the presence of two biliary anastomoses and post-transplant complications including acute cellular rejection and early biliary leaks were associated with biliary strictures in pediatric liver transplantation recipients. Percutaneous transhepatic interventions result in good outcomes in most patients.

Cell-based BSEP trans-inhibition: A novel, non-invasive test for diagnosis of antibody-induced BSEP deficiency.

Background & Aims: Antibody-induced bile salt export pump deficiency (AIBD) is an acquired form of intrahepatic cholestasis, which may develop following orthotopic liver transplantation (OLT) for progressive familial intrahepatic cholestasis type 2 (PFIC-2). Approximately 8-33% of patients with PFIC-2 who underwent a transplant develop bile salt export pump (BSEP) antibodies, which trans-inhibit this bile salt transporter from the extracellular, biliary side. AIBD is diagnosed by demonstration of BSEP-reactive and BSEP-inhibitory antibodies in patient serum. We developed a cell-based test directly measuring BSEP trans-inhibition by antibodies in serum samples to confirm AIBD diagnosis. Methods: Sera from healthy controls and cholestatic non-AIBD or AIBD cases were tested (1) for anticanalicular reactivity by immunofluorescence staining of human liver cryosections, (2) for anti-BSEP reactivity by immunofluorescence staining of human embryonic kidney 293 (HEK293) cells expressing BSEP-enhanced yellow fluorescent protein (EYFP) and immunodetection of BSEP-EYFP on Western blot, and (3) for BSEP trans-inhibition using HEK293 cells stably expressing Na+/taurocholate cotransporting polypeptide (NTCP)-mCherry and BSEP-EYFP. The trans-inhibition test uses [3H]-taurocholate as substrate and is divided into an uptake phase dominated by NTCP followed by BSEP-mediated export. For functional analysis, sera were bile salt depleted. Results: We found BSEP trans-inhibition by seven sera containing anti-BSEP antibodies, but not by five cholestatic or nine control sera, all lacking BSEP reactivity. Prospective screening of a patient with PFIC-2 post OLT showed seroconversion to AIBD, and the novel test method allowed monitoring of treatment response. Notably, we identified a patient with PFIC-2 post OLT with anti-BSEP antibodies yet without BSEP trans-inhibition activity, in line with asymptomatic presentation at serum sampling. Conclusions: Our cell-based assay is the first direct functional test for AIBD and allows confirmation of diagnosis as well as monitoring under therapy. We propose an updated workflow for AIBD diagnosis including this functional assay. Impact and Implications: Antibody-induced BSEP deficiency (AIBD) is a potentially serious complication that may affect patients with PFIC-2 after liver transplantation. To improve its early diagnosis and thus immediate treatment, we developed a novel functional assay to confirm AIBD diagnosis using a patient's serum and propose an updated diagnostic algorithm for AIBD.

Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency.

Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p <0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p <0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.

Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants.

PURPOSE: This study aimed to define the genotypic and phenotypic spectrum of reversible acute liver failure (ALF) of infancy resulting from biallelic pathogenic TRMU variants and determine the role of cysteine supplementation in its treatment. METHODS: Individuals with biallelic (likely) pathogenic variants in TRMU were studied within an international retrospective collection of de-identified patient data. RESULTS: In 62 individuals, including 30 previously unreported cases, we described 47 (likely) pathogenic TRMU variants, of which 17 were novel, and 1 intragenic deletion. Of these 62 individuals, 42 were alive at a median age of 6.8 (0.6-22) years after a median follow-up of 3.6 (0.1-22) years. The most frequent finding, occurring in all but 2 individuals, was liver involvement. ALF occurred only in the first year of life and was reported in 43 of 62 individuals; 11 of whom received liver transplantation. Loss-of-function TRMU variants were associated with poor survival. Supplementation with at least 1 cysteine source, typically N-acetylcysteine, improved survival significantly. Neurodevelopmental delay was observed in 11 individuals and persisted in 4 of the survivors, but we were unable to determine whether this was a primary or a secondary consequence of TRMU deficiency. CONCLUSION: In most patients, TRMU-associated ALF was a transient, reversible disease and cysteine supplementation improved survival.

Acute Hepatitis of Unknown Etiology Among Young Children: Research Agenda by the ESPGHAN Hepatology Committee.

In April 2022, an increased incidence of acute hepatitis cases of unknown etiology among previously healthy children across the United Kingdom was described. Since, more than 270 cases from the United Kingdom and hundreds more from all across the world have been reported. The majority of affected children were younger than 6 years of age. The clinical presentation was nonspecific with diarrhea and vomiting usually preceding the appearance of jaundice, abdominal pain, nausea, and malaise. Approximately 5% have required liver transplantation. An infectious etiology has been considered likely given the epidemiological and clinical features of the reported cases. Between 50 and 60% of the children tested were diagnosed with adenovirus infection although a clear etiological connection has still to be demonstrated. No link with SARS-CoV-2 infection and COVID-19 vaccine was found. What is not clear to date is whether the high number of acute hepatitis cases reported is related to a true increase in incidence or heightened awareness following on from the initial reports from the United Kingdom. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed a paper on the current outbreak of acute hepatitis of unknown etiology recognizing its importance and the need of approaching the current situation with a scientifically rigorous approach. The aims of the article are to summarize the current knowledge and to identify the most pertinent issues regarding the diagnosis and management of this condition and the research questions raised.

Long COVID-19 Liver Manifestation in Children.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2, the novel coronavirus responsible for coronavirus disease (COVID-19), has been a major cause of morbidity and mortality worldwide. Gastrointestinal and hepatic manifestations during acute disease have been reported extensively in the literature. Post-COVID-19 cholangiopathy has been increasingly reported in adults. In children, data are sparse. Our aim was to describe pediatric patients who recovered from COVID-19 and later presented with liver injury. METHODS: This is a retrospective case series study of pediatric patients with post-COVID-19 liver manifestations. We collected data on demographics, medical history, clinical presentation, laboratory results, imaging, histology, treatment, and outcome. RESULTS: We report 5 pediatric patients who recovered from COVID-19 and later presented with liver injury. Two types of clinical presentation were distinguishable. Two infants aged 3 and 5 months, previously healthy, presented with acute liver failure that rapidly progressed to liver transplantation. Their liver explant showed massive necrosis with cholangiolar proliferation and lymphocytic infiltrate. Three children, 2 aged 8 years and 1 aged 13 years, presented with hepatitis with cholestasis. Two children had a liver biopsy significant for lymphocytic portal and parenchyma inflammation, along with bile duct proliferations. All 3 were started on steroid treatment; liver enzymes improved, and they were weaned successfully from treatment. For all 5 patients, extensive etiology workup for infectious and metabolic etiologies was negative. CONCLUSIONS: We report 2 distinct patterns of potentially long COVID-19 liver manifestations in children with common clinical, radiological, and histopathological characteristics after a thorough workup excluded other known etiologies.

Portal plate bile duct diameter in biliary atresia is associated with long-term outcome.

PURPOSE: Kasai portoenterostomy (KPE) is the only treatment currently available for biliary atresia (BA). Age at KPE and surgical experience are prognostic factors for a successful KPE. Here, we aimed to assess whether the size of bile ductules at the porta hepatis during KPE correlates with KPE success and transplant-free survival (TFS). METHODS: A retrospective analysis of patients diagnosed with BA during 2000-2019. Porta hepatis biopsies were reviewed for diameters of five representative ducts, and a mean ductal diameter (MDD) was calculated. Laboratory values including pre- and postoperative bilirubin levels were analyzed. RESULTS: The cohort included 77 patients; for 33, ductal plate biopsy was available. KPE was successful in six of eight patients with MDD ≥ 50 µm, and in five of 25 with MDD < 50 µm, p = 0.008, OR = 12.0 (95% CI 1.83-78.3). Ten-year survival with native liver was higher in patients with MDD ≥ 50 µm than in patients with MDD < 50 µm, p < 0.001, HR 0.038 (95% CI 0.007-0.207). Direct bilirubin < 1 mg/dl 3 months post-KPE was associated with improved 2-year post-KPE TFS (27.7% vs. 13.9%, p < 0.0001). CONCLUSIONS: MDD ≥ 50 µm correlates with KPE success and a higher rate of TFS. Direct bilirubin < 1 mg/dl 3 months post-operation may serve as a marker of successful biliary excretion, and a predictor of 2-year TFS.

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

BACKGROUND AND AIMS: Mutations in ATPase phospholipid transporting 8B1 (ATP8B1) can lead to familial intrahepatic cholestasis type 1 (FIC1) deficiency, or progressive familial intrahepatic cholestasis type 1. The rarity of FIC1 deficiency has largely prevented a detailed analysis of its natural history, effects of predicted protein truncating mutations (PPTMs), and possible associations of serum bile acid (sBA) concentrations and surgical biliary diversion (SBD) with long-term outcome. We aimed to provide insights by using the largest genetically defined cohort of patients with FIC1 deficiency to date. APPROACH AND RESULTS: This multicenter, combined retrospective and prospective study included 130 patients with compound heterozygous or homozygous predicted pathogenic ATP8B1 variants. Patients were categorized according to the number of PPTMs (i.e., splice site, frameshift due to deletion or insertion, nonsense, duplication), FIC1-A (n = 67; no PPTMs), FIC1-B (n = 29; one PPTM), or FIC1-C (n = 34; two PPTMs). Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12), despite FIC1-C undergoing SBD less often (% SBD at age 10 years: 65%, 57%, and 45%, respectively; P = 0.03). sBAs at presentation were negatively associated with NLS (NLS at age 10 years, sBAs < 194 µmol/L: 49% vs. sBAs ≥ 194 µmol/L: 15%; P = 0.03). SBD decreased sBAs (230 [125-282] to 74 [11-177] µmol/L; P = 0.005). SBD (HR 0.55, 95% CI 0.28-1.03, P = 0.06) and post-SBD sBA concentrations < 65 µmol/L (P = 0.05) tended to be associated with improved NLS. CONCLUSIONS: Less than half of patients with FIC1 deficiency reach adulthood with native liver. The number of PPTMs did not associate with the natural history or prognosis of FIC1 deficiency. sBA concentrations at initial presentation and after SBD provide limited prognostic information on long-term NLS.

Clinical and Esophagogastroduodenoscopy Findings in Pediatric Patients With Severe Obesity Evaluated Before Bariatric Surgery.

OBJECTIVES: Severe obesity in the pediatric population has lifelong consequences. Bariatric surgery has been suggested for selected adolescents with severe obesity after careful evaluation. The indications for preoperative esophagogastroduodenoscopy (EGD) in this age group are not clear, despite its established usefulness in adults. We aimed to assess the usefulness of EGD before bariatric surgery in pediatric patients with severe obesity and metabolic comorbidities. METHODS: We conducted a retrospective chart review in a single tertiary pediatric medical center of adolescents treated during 2011 to 2018. Data collected from electronic medical records included patient demographics, endoscopic findings, and laboratory parameters. RESULTS: A total of 80 patients (40 boys) underwent evaluation. Macroscopic abnormalities were detected in 54% of the endoscopies, including gastritis, esophagitis, and duodenitis in 46%, 16%, and 13%, respectively. Forty-nine percentage of the biopsies showed histological abnormalities; in 35 (44%) patients, Helicobacter pylori was detected. Thirty-three patients (41%) received medical treatment and 2 (2.5%) required a second EGD. Metabolic comorbidities included hypertriglyceridemia (38% of the patients), low high-density lipoprotein (23%), and prediabetic (16%) or diabetic levels of HbA1C (4%). Fifty-five percentage of the cohort had elevated alanine aminotransferase (ALT), suggestive of nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: Endoscopies performed before bariatric surgeries suggest a higher prevalence of clinically significant findings, many of which required treatment. These findings support incorporating an EGD into the preoperative evaluation of this patient population.

Adenosine kinase deficiency: Three new cases and diagnostic value of hypermethioninemia.

Adenosine kinase (ADK) deficiency is characterized by liver disease, dysmorphic features, epilepsy and developmental delay. This defect disrupts the adenosine/AMP futile cycle and interferes with the upstream methionine cycle. We report the clinical, histological and biochemical courses of three ADK children carrying two new mutations and presenting with neonatal cholestasis and neurological disorders. One of them died of liver failure whereas the other two recovered from their liver damage. As the phenotype was consistent with a mitochondrial disorder, we studied liver mitochondrial respiratory chain activities in two patients and revealed a combined defect of several complexes. In addition, we retrospectively analyzed methionine plasma concentration, a hallmark of ADK deficiency, in a cohort of children and showed that methionine level in patients with ADK deficiency was strongly increased compared with patients with other liver diseases. ADK deficiency is a cause of neonatal or early infantile liver disease that may mimic primary mitochondrial disorders. In this context, an elevation of methionine plasma levels over twice the upper limit should not be considered as a nonspecific finding. ADK deficiency induced-liver dysfunction is most often transient, but could be life-threatening.

Genotype correlates with the natural history of severe bile salt export pump deficiency.

BACKGROUND & AIMS: Mutations in ABCB11 can cause deficiency of the bile salt export pump (BSEP), leading to cholestasis and end-stage liver disease. Owing to the rarity of the disease, the associations between genotype and natural history, or outcomes following surgical biliary diversion (SBD), remain elusive. We aimed to determine these associations by assembling the largest genetically defined cohort of patients with severe BSEP deficiency to date. METHODS: This multicentre, retrospective cohort study included 264 patients with homozygous or compound heterozygous pathological ABCB11 mutations. Patients were categorized according to genotypic severity (BSEP1, BSEP2, BSEP3). The predicted residual BSEP transport function decreased with each category. RESULTS: Genotype severity was strongly associated with native liver survival (NLS, BSEP1 median 20.4 years; BSEP2, 7.0 years; BSEP3, 3.5 years; p <0.001). At 15 years of age, the proportion of patients with hepatocellular carcinoma was 4% in BSEP1, 7% in BSEP2 and 34% in BSEP3 (p = 0.001). SBD was associated with significantly increased NLS (hazard ratio 0.50; 95% CI 0.27-0.94: p = 0.03) in BSEP1 and BSEP2. A serum bile acid concentration below 102 µmol/L or a decrease of at least 75%, each shortly after SBD, reliably predicted NLS of ≥15 years following SBD (each p <0.001). CONCLUSIONS: The genotype of severe BSEP deficiency strongly predicts long-term NLS, the risk of developing hepatocellular carcinoma, and the chance that SBD will increase NLS. Serum bile acid parameters shortly after SBD can predict long-term NLS. LAY SUMMARY: This study presents data from the largest genetically defined cohort of patients with severe bile salt export pump deficiency to date. The genotype of patients with severe bile salt export pump deficiency is associated with clinical outcomes and the success of therapeutic interventions. Therefore, genotypic data should be used to guide personalized clinical care throughout childhood and adulthood in patients with this disease.

Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies.

Reactivation of hepatitis B virus (HBV) is a known complication of immune-suppressive, cytotoxic, and biological modifier therapies in patients currently infected with HBV or who have had past exposure to HBV. Nowadays, newer and emerging forms of targeted biologic therapies are available for the management of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions and solid-organ, bone marrow, or haematologic stem cell transplant but there is currently a lack of a systematic approach to the care of patients with or at risk of HBV reactivation. The Hepatology Committee of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) together with a working group of ESPGHAN members with clinical and research expertise in viral hepatitis developed an evidence-based position paper on reactivation of HBV infection in children identifying pertinent issues addressing the diagnosis, prevention, and treatment of this condition. Relevant clinical questions were formulated and agreed upon by all the members of the working group. Questions were answered and positions were based on evidence resulting from a systematic literature search on PubMed and Embase from their inception to July 1, 2019. A document was produced and the working group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique. A recommendation was accepted provided upon agreement by at least 75% of the working group members. This position paper provides a comprehensive update on the diagnosis, prevention and treatment of HBV reactivation in children.

The Israel Defense Forces experience with freeze-dried plasma for the resuscitation of traumatized pediatric patients.

BACKGROUND: With the growing recognition of the disadvantages of crystalloid- and colloid-based resuscitation and the advantages of using blood products as the preferred resuscitation fluid, the Israel Defense Forces Medical Corps (IDF-MC) adopted plasma as the primary volume resuscitation regimen in 2013. While data are accumulating for prehospital plasma transfusion, little to no data exist regarding using plasma as a prehospital resuscitation fluid for traumatized pediatric patients. METHODS: All patients treated by the IDF-MC personnel are recorded in the IDF Trauma Registry, a unique prehospital trauma registry. All patients treated by the IDF advanced life support providers with FDP at the point of injury between April 2013 and June 2018 who were younger than 18 years at the time of injury were included. RESULTS: Six hundred seventy-nine children were treated by IDF medical providers, of whom 33 (5%) were identified in the IDF Trauma Registry as having received FDP at the point of injury. Most patients (80%) were treated for penetrating injuries. Most patients received one plasma unit. Fifty-four percent of the patients were also treated by Tranexamic Acid (TXA) and 48% were transfused with crystalloids. In 33% of patients, additional life-saving interventions were performed. CONCLUSION: While the ideal resuscitation fluid for the pediatric population remains to be determined, it seems reasonable to pursue a similar approach to that of applied that for adults. In the IDF-MC, the resuscitation fluid of choice for trauma patients in hemorrhagic shock is freeze-dried plasma transfused at the point of injury. The current study demonstrates the feasibility of FDP administration in the prehospital scenario for injured children and further supports the growing confidence in the use of FDP for the treatment of pediatric trauma patients. LEVEL OF EVIDENCE: Retrospective descriptive study, level IV.

Prevalence of acute kidney injury after liver transplantation in children: Comparison of the pRIFLE, AKIN, and KDIGO criteria using corrected serum creatinine.

PURPOSE: To compare the application of three standardized definitions of acute kidney injury (AKI), using corrected serum creatinine values, in children immediately after liver transplantation. METHODS: Retrospective search of a tertiary pediatric hospital database yielded 77 patients (age < 18 years) who underwent liver transplantation in 2007-2017. Serum creatinine levels during the 24 h before and after surgery were corrected to daily fluid balance, and the prevalence of AKI was calculated using the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria. RESULTS: AKI occurred in 44 children (57%) according to the pRIFLE criteria (stage I, 34%; stage II, 10%, stage III, 13%) and 33 children (43%) according to the AKIN and KDIGO criteria (stage I, 20%; stage II, 10%; stage III, 13%). There was a good correlation (kappa = 0.78) among the three criteria. AKI was associated with longer duration of mechanical ventilation (5.5 ±â€¯6.2 vs 3.6 ±â€¯4.0 days, p < .05) and longer ICU stay (15.2 ±â€¯8.8 vs 12.1 ±â€¯7.5 days, p < .05). Serum creatinine normalized in all patients (mean, 0.43 ±â€¯0.17 mg/dl) by one year. CONCLUSIONS: There is a good correlation among the three criteria defining AKI in pediatric liver transplant recipients. AKI is highly prevalent in this patient group and confers a worse ICU course.

Primary infection with human herpes virus type 6, post-pediatric liver transplantation-A pathogen to remember.

BACKGROUND: In recent years, liver transplantation (LT) has become a well-accepted therapeutic modality for children with end-stage liver disease, with transplantation surgery being performed at a younger age. Human herpes virus 6 (HHV-6) infection occurs in most children within the first 2 years of life, therefore, data on primary HHV-6 infection in pediatric liver transplant recipients is scarce. OBJECTIVE: To describe the course of primary HHV-6 infection after pediatric LT. METHODS: Medical files, between the years 2015-2016, of post-LT pediatric patients with suspected primary HHV-6 infection were reviewed. Clinical and laboratory data for enrolled cases were evaluated. Primary infection was defined as DNAemia in children who were seronegative prior to transplantation or seroconversion from negative to positive IgG posttransplantation. RESULTS: Four cases of primary HHV-6 (type B) infection were identified among the 26 children who had undergone LT at our center during the study period. All patients were <1 year old and presented with fever, hepatitis, and elevated inflammatory markers, most (75%) within a short-period posttransplantation. All were initially treated with empiric antibiotics for a suspected bacterial infection and three underwent liver biopsy, one showing signs of rejection. Three were treated with antiviral therapy with a gradual resolution of symptoms. DISCUSSION: Primary HHV-6 should be taken into account in young children shortly after LT, especially when presenting with fever and elevated liver enzymes. Treatment with antiviral therapy should be considered. CONCLUSIONS: In young infants post-LT, a high index of suspicion may promote early detection of HHV-6 primary infection and prevent serious complications.

Predictors of pouchitis after ileal pouch-anal anastomosis in pediatric-onset ulcerative colitis.

OBJECTIVES: Few studies have reported on the incidence and risk factors for pouchitis following colectomy and ileal pouch-anal anastomosis (IPAA) in patients with pediatric-onset ulcerative colitis (UC). We aimed to determine clinical predictors for the development of pouchitis following IPAA in this population. PATIENTS AND METHODS: We performed a retrospective chart review of all pediatric UC cases that were diagnosed at the Schneider Children's Medical Center of Israel between 1981 and 2013 and who underwent colectomy during disease course. Potential predictors for pouchitis and chronic pouchitis including various demographic, clinical, endoscopic, and histological variables at diagnosis and at the time of surgery were assessed. RESULTS: Of 188 patients with pediatric-onset UC, 33 (18%) underwent colectomy and IPAA surgery. During a median postsurgical follow-up of 7.6 (range: 1-21.5) years following IPAA, 20/33 (60%) patients developed pouchitis including 11/33 (33%) patients who developed chronic pouchitis. Kaplan-Meier survival estimates of the cumulative probability for pouchitis were 9% at 1 year and 36 and 55% at 5 and 10 years, respectively. Multivariate Cox models showed that older age at colectomy (hazard ratio: 0.86, P=0.024) was a protective factor, whereas preoperative vitamin-D deficiency (≤20 ng/ml) (hazard ratio: 4.4, P=0.021) increased the risk for pouchitis. Age at diagnosis, sex, disease extent, and preoperative therapeutic regimens did not affect the risk of pouchitis. CONCLUSION: Long-term risk for pouchitis is significantly high in pediatric-onset UC after IPAA. Vitamin-D deficiency and younger age at colectomy may increase the risk for pouchitis.

Oesophageal eosinophilia in children with coeliac disease.

OBJECTIVES: An association between coeliac disease (CD) and eosinophilic oesophagitis (EoE)/oesophageal eosinophilia (EE) has been suggested. We sought to characterise children with CD+EE in-depth and assess the contribution of each condition to the clinical presentation and treatment response. STUDY DESIGN: Medical records of children with both CD+EE, or isolated EoE diagnosed between 2000 and 2014, were retrospectively reviewed and compared with patients with isolated CD or epigastric pain. Frequency of EE was calculated from endoscopy results of patients with suspected CD or epigastric pain between 2011 and 2014. Missing data were obtained via a telephone questionnaire. SETTING: Single large, tertiary paediatric centre. PATIENTS: 17 CD+EE, 46 EoE, 302 isolated CD and 247 epigastric pain. RESULTS: The patients with CD+EE shared characteristics of both individual conditions. While age at diagnosis, family history of autoimmunity/CD and anaemia were similar to patients with CD, other characteristics such as male gender, personal/family history of atopy, peripheral eosinophilia and oesophageal white papules were more similar to patients with EoE. Combined patients (CD+EE) tended to present with CD-associated symptoms; the majority (63%) later developed typical EoE symptoms. Only a minority (21%) of combined patients had EE that resolved after a gluten-free diet; another 21% had normalisation of EE upon proton pump inhibitor treatment. The remainder required EoE-specific treatment. CONCLUSION: Patients with CD found to have EE share characteristics with both isolated CD and EoE. It appears that these are two coexisting entities presenting in the same patient rather than eosinophilia associated with CD, and therefore, interventions separately addressing each condition may be considered.

Risk of Colectomy in Patients With Pediatric-onset Ulcerative Colitis.

OBJECTIVES: Data describing the incidence and risk factors for colectomy in pediatric ulcerative colitis (UC) is inconsistent. Our aim was to describe the colectomy rate and to identify risk factors associated with colectomy in a large cohort of children with UC with long-term follow-up. MATERIALS AND METHODS: We performed a retrospective chart review of pediatric UC cases that were diagnosed at Schneider Children's Medical Center of Israel between 1981 and 2013. Potential predictors for colectomy including age at diagnosis, sex, disease extent, severity indices, and different therapeutic regimens during disease course were assessed. RESULTS: Of 188 patients with pediatric onset UC, 34 (18%) underwent colectomy. Median follow-up was 6.9 years (range, 1-30). Kaplan-Meier survival estimates of the cumulative probability for colectomy were 4% at 1 year and 17% at 10 years from diagnosis. Multivariate Cox models showed that male sex (hazard ratio 4.2, P = 0.001) and severe disease at diagnosis reflected by Pediatric Ulcerative Colitis Activity Index score ≥65 (hazard ratio 8.9, P < 0.001) were associated with increased risk for colectomy. Age, disease extent, ethnicity, family history of inflammatory bowel disease, early introduction of immunomodulators, or treatment with antitumor necrosis factor α agent did not affect the risk of colectomy. CONCLUSIONS: Male sex and higher Pediatric Ulcerative Colitis Activity Index score at diagnosis are independent risk factors for colectomy.