Acute pancreatitis in children with inflammatory bowel disease: Risk factors, clinical course, and prognosis.

OBJECTIVES: To characterize the clinical course of acute pancreatitis (AP) in pediatric inflammatory bowel disease (IBD) patients compared to children with AP without IBD and to identify risk factors associated with AP among IBD patients. METHODS: This retrospective, single-center study compared clinical characteristics of children (<19 years) with AP with and without concomitant IBD who were hospitalized 2005-2019. We also conducted a risk factor analysis of AP development in pediatric IBD. RESULTS: Sixty-eight (54% males) patients with 120 episodes of AP were admitted at a median age of 15.3 years. Thirteen patients (14 episodes) had a co-diagnosis of IBD, representing 4% of our IBD patient population. The AP-IBD patients presented with lower amylase levels compared to the non-IBD patients (160 [interquartile range, IQR: 83-231] vs. 418 [IQR: 176-874] U/L, p > 0.01), all had a mild pancreatitis, and none required invasive intervention. The presumed etiology for AP in all IBD patients was IBD-related: IBD flare-up in five, side effects of medications in two, and undetermined in seven. The only risk factor for AP development among IBD patients was IBD-associated arthritis (23% vs. 3% for IBD-non-AP, p = 0.04), while extracolonic Crohn's disease and induction therapy with nutrition were negative risk factors (15% vs. 51%, p = 0.05, and 8% vs. 44%, p = 0.04, respectively). Other parameters, including disease type and medications, were nonsignificant. CONCLUSION: The clinical course of AP in pediatric IBD patients is mild. Only IBD-associated arthritis emerged as a risk factor for the development of AP, while, unexpectedly, IBD medication did not.

The Yield of Routine Tissue Sampling in Pediatric Gastrointestinal Endoscopy.

OBJECTIVES: Societies' guidelines suggest routine tissue sampling in all children undergoing esophagogastroduodenoscopy and ileocolonoscopy, even in the absence of visible endoscopy abnormalities. We aimed to determine the agreement between endoscopic and histopathological findings in pediatric endoscopy and to assess the yield of routine biopsies from all sites. METHODS: Since January 2019, our endoscopy institute protocol has included routine biopsies sampling from the esophagus, stomach, duodenum, ileum, and colon in all diagnostic procedures. Agreement between tests was done using the kappa coefficient ( κ ). The study included all endoscopies performed during 2019. RESULTS: In total, 541 diagnostic endoscopies were done during the study period with 434 (80%) esophagogastroduodenoscopy and 107 (20%) were ileocolonoscopy. Compared to histology, endoscopic findings performance were: esophagus-sensitivity 33%, specificity 98%; stomach-sensitivity 60%, specificity 89%; duodenum-sensitivity 50%, specificity 97%; duodenal bulb-sensitivity 47%, specificity 89%; terminal ileum-sensitivity 82%, specificity 100%; colon-sensitivity 84%, specificity 96%. Assessment of concordance between endoscopic and histopathologic findings reveals an overall low level of agreement in esophagogastroduodenoscopy ( κ of 0.39, 0.51, 0.53, and 0.24 for the esophagus, stomach, duodenal second part, and bulb, respectively), and good agreement in ileocolonoscopy ( κ of 0.88 and 0.81 for the ileum and colon, respectively). CONCLUSIONS: Endoscopy findings are highly specific for histologic pathology, whereas the absence of findings correlates poorly with histologic findings. Ileocolonoscopy shows better agreement than esophagogastroduodenoscopy. Our data support routine tissue sampling in pediatric endoscopy.

Bacterial resistance to commonly prescribed antibiotics was rare among children hospitalised for clinical dysentery.

AIM: Temporal changes in common pathogens that cause clinical dysentery have been described in Europe. We aimed to describe the distribution of pathogens and their antibiotic resistance in hospitalised Israeli children. METHODS: This study retrospectively studied children hospitalised for clinical dysentery, with or without a positive stool culture, from 1 January 2016 to 31 December 2019. RESULTS: We diagnosed 137 patients (65% males), with clinical dysentery at a median age of 3.7 (interquartile range 1.5-8.2) years. Stools were cultured in 135 patients (99%), and the results were positive in 101 (76%). These comprised Campylobacter (44%), Shigella sonnei (27%), non-typhoid Salmonella (18%) and enteropathogenic Escherichia coli (12%). Only one of the 44 Campylobacter cultures was resistant to erythromycin and one of the 12 enteropathogenic Escherichia coli cultures was resistant to ceftriaxone. None of the Salmonella and Shigella cultures were resistant to ceftriaxone or erythromycin. We did not find any pathogens that were associated with a typical clinical presentation or laboratory results on admission. CONCLUSION: The most common pathogen was Campylobacter, in line with recent European trends. Bacterial resistance for commonly prescribed antibiotics was rare, and these findings support the current European recommendations.

Oral Vancomycin, Ursodeoxycholic Acid, or No Therapy for Pediatric Primary Sclerosing Cholangitis: A Matched Analysis.

BACKGROUND AND AIMS: Many children with primary sclerosing cholangitis (PSC) receive oral vancomycin therapy (OVT) or ursodeoxycholic acid (UDCA). There is a paucity of data on whether these medications improve outcomes. APPROACH AND RESULTS: We analyzed retrospective data from the Pediatric PSC Consortium. Children treated with OVT were matched 1:1:1 to those treated with UDCA or managed with observation (no treatment) based on the closest propensity score, ensuring similar baseline characteristics. Two hundred sixty-four patients (88 each with OVT, UDCA, or observation) had matching propensity scores and were similar in demographics, phenotype, immunosuppression, baseline biochemistry, and hepatic fibrosis. After 1 year in an intention-to-treat analysis, all outcome metrics were similar regardless of treatment group. In OVT, UDCA, and untreated groups, respectively: Gamma-glutamyltransferase normalized in 53%, 49%, and 52% (P = not significant [NS]), liver fibrosis stage was improved in 20%, 13%, and 18% and worsened in 11%, 29%, and 18% (P = NS), and the 5-year probability of liver transplant listing was 21%, 10%, and 12% (P = NS). Favorable outcome was associated with having a mild phenotype of PSC and minimal hepatic fibrosis. CONCLUSIONS: We presented the largest-ever description of outcomes on OVT in PSC and compared them to carefully matched patients on UDCA or no therapy. Neither OVT nor UDCA showed improvement in outcomes compared to a strategy of observation. Patients progressed to end-stage liver disease at similar rates. Spontaneous normalization of biochemistry is common in children receiving no therapy, particularly in the majority of children with a mild phenotype and an early stage of disease. Placebo-controlled treatment trials are needed to identify effective treatments for pediatric PSC.

The Sclerosing Cholangitis Outcomes in Pediatrics (SCOPE) Index: A Prognostic Tool for Children.

BACKGROUND AND AIMS: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. APPROACH AND RESULTS: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of <1%, 3%, and 9% annually and to HBCs at rates of 2%, 6%, and 13% annually, respectively (P < 0.001). C-statistics to discriminate outcomes at 1 and 5 years were 0.95 and 0.82 for TD and 0.80 and 0.76 for HBCs, respectively. Baseline hepatic fibrosis stage was worse with increasing risk score, with extensive fibrosis in 8% of the lowest versus 100% with the highest risk index (P < 0.001). The model was validated in 240 children from 11 additional centers and performed well. CONCLUSIONS: The SCOPE index is a pediatric-specific prognostic tool for PSC. It uses routinely obtained, objective data to predict a complicated clinical course. It correlates strongly with biopsy-proven liver fibrosis. SCOPE can be used with families for shared decision making on clinical care based on a patient's individual risk, and to account for variable disease progression when designing future clinical trials.

Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study.

Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3 months and all within 1 year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.

Increasing rate of a positive family history of inflammatory bowel disease (IBD) in pediatric IBD patients.

The role of a positive family history in pediatric inflammatory bowel disease (IBD) in the era of biologic therapy has not been elucidated. We retrospectively reviewed the medical records of children with IBD and retrieved demographic and clinical characteristics, including the presence of a positive family history of IBD, IBD phenotype, disease course, and therapy. Overall, 325 children (age range at diagnosis 11-15 years) were included, of whom 82 (25.2%) had a positive family history. Children diagnosed during 2016-2020 had a higher frequency of positive family history compared to those diagnosed during 2010-2015 (31.8% versus 20.7%, respectively, p = 0.024). Children with a positive family history had a higher risk for a stricturing phenotype than those with a negative family history (11.3% versus 2.8%, respectively, p = 0.052). They more often received nutritional therapy (53.7% versus 36.6%, p = 0.007) and less often received corticosteroids (36.6% versus 52.7%, p = 0.012). More children with a negative family history needed intensification of biologic therapy (p = 0.041).Conclusion: The rate of a positive family history of IBD in the pediatric IBD population is increasing. A positive family history may have some impact upon IBD phenotype but none on IBD outcome. What is Known: •Familial clustering of inflammatory bowel disease (IBD) has been reported in 5%-15% of IBD patients. •The investigation of the impact of a positive family history upon IBD characteristics and severity revealed conflicting results. What is New: •In this cohort of 325 children with IBD, 25.2% had a positive family history. •The rate of a positive family history of IBD in the pediatric IBD population is increasing. •A positive family history may have some impact upon IBD phenotype but none on IBD outcome.

Colorectal Dysplasia and Cancer in Pediatric-Onset Ulcerative Colitis Associated With Primary Sclerosing Cholangitis.

Inflammatory bowel disease (IBD), especially when associated with primary sclerosing cholangitis (PSC), is a risk factor for developing colorectal cancer (CRC).1-3 We aimed to determine the incidence of CRC in a large cohort of pediatric-onset PSC-ulcerative colitis (UC) patients.

A recurrent, homozygous EMC10 frameshift variant is associated with a syndrome of developmental delay with variable seizures and dysmorphic features.

PURPOSE: The endoplasmic reticulum membrane complex (EMC) is a highly conserved, multifunctional 10-protein complex related to membrane protein biology. In seven families, we identified 13 individuals with highly overlapping phenotypes who harbor a single identical homozygous frameshift variant in EMC10. METHODS: Using exome, genome, and Sanger sequencing, a recurrent frameshift EMC10 variant was identified in affected individuals in an international cohort of consanguineous families. Multiple families were independently identified and connected via Matchmaker Exchange and internal databases. We assessed the effect of the frameshift variant on EMC10 RNA and protein expression and evaluated EMC10 expression in normal human brain tissue using immunohistochemistry. RESULTS: A homozygous variant EMC10 c.287delG (Refseq NM_206538.3, p.Gly96Alafs*9) segregated with affected individuals in each family, who exhibited a phenotypic spectrum of intellectual disability (ID) and global developmental delay (GDD), variable seizures and variable dysmorphic features (elongated face, curly hair, cubitus valgus, and arachnodactyly). The variant arose on two founder haplotypes and results in significantly reduced EMC10 RNA expression and an unstable truncated EMC10 protein. CONCLUSION: We propose that a homozygous loss-of-function variant in EMC10 causes a novel syndromic neurodevelopmental phenotype. Remarkably, the recurrent variant is likely the result of a hypermutable site and arose on distinct founder haplotypes.

BMI in the lower and upper quartiles at diagnosis and at 1-year follow-up is significantly associated with higher risk of disease exacerbation in pediatric inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition, but obesity may also serve as a negative prognostic factor. This study aimed to present the longitudinal course of height, weight, and body mass index (BMI) of children from IBD diagnosis to 18 months of follow-up, and to describe the impact of BMI on the clinical course of the disease. One hundred and fifty-two children were identified, of whom 85 had Crohn's disease (CD) and 67 had ulcerative colitis (UC). During a median (interquartile range) follow-up of 2.95 (1.73-4.5) years, weight and BMI Z-scores increased in the first 18 months since diagnosis in both the CD (P < 0.001) and UC (P < 0.028) groups. BMI in lower and upper quartiles at diagnosis was associated with higher risk of hospitalization (hazard ratio [HR] = 2.72, P = 0.021). In a multivariate analysis, BMI in the lower quartile at diagnosis and at 6, 12, and 18 months was associated with higher risk of disease exacerbation (HR = 2.36, 1.90, 1.98, and 2.43, respectively, P < 0.021), as was BMI in the upper quartile (HR = 2.59, 2.91, and 2.29, respectively, P < 0.013).Conclusion: BMI in the lower and upper quartiles at diagnosis and during follow-up was associated with a more severe disease course in children with IBD. What is Known: • Inflammatory bowel disease (IBD) has been associated with underweight and malnutrition. • The impacts of weight and body mass index (BMI) on the presentation and course of IBD have been mainly investigated in the adult population. What is New: • In the era of the obesity epidemic, this study identifies both low and high BMIs at diagnosis and at follow-up as a marker for poor outcome in pediatric IBD. • The results support using BMI as a predictor of IBD course and prognosis.

Higher BMI predicts liver fibrosis among obese children and adolescents with NAFLD - an interventional pilot study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) can range from simple steatosis to steatohepatitis with or without fibrosis. The predictors for liver fibrosis and the effect of nutritional intervention on hepatic fibrosis in pediatric population are not well established. We aimed to investigate the predictors for liver fibrosis and the effects of short-term nutritional intervention on steatosis and fibrosis among obese adolescents with NAFLD. METHODS: Cross-sectional study among obese adolescents. Sociodemographic and clinical data were collected. Liver fibrosis was estimated by Shearwave elastography. All participants were recommended to consume a low carbohydrate diet and were followed biweekly. Blood tests and elastography were performed upon admission and repeated after 3 months. RESULTS: Fifty-seven pediatric patients were recruited (35 males, mean age 13.5±2.9 years, mean body mass index [BMI] 38.8±9.7). Liver fibrosis was diagnosed in 34 (60%) subjects, which was moderate/severe (F≥2) in 24 (70%). A higher BMI Z score and moderate/severe steatosis correlated with moderate/severe fibrosis (P < 0.05). Seventeen patients completed 3 months of follow-up and displayed a decrease in BMI Z score (from BMI Z score 2.6±0.5 before intervention to 2.4±0.5 after intervention), with a significant decrease in liver fibrosis (P = 0.001). CONCLUSION: Pediatric patients with high BMIs and severe liver steatosis are at risk for severe liver fibrosis. Nutritional intervention with minimal weight loss may improves hepatic fibrosis among the pediatric population. TRIAL REGISTRATION: TRN NCT04561804 (9/17/2020).

The effect of gluten-free diet on body mass index in paediatric celiac disease.

AIM: More normal weight and overweight children are currently diagnosed with celiac disease (CD). We aimed to describe the relation between body mass index (BMI) and the clinical characteristics of paediatric CD and to determine the effect of a gluten-free diet (GFD) on BMI. METHODS: Data on all children diagnosed with CD during 7/2010-7/2019 with documented anthropometric data at diagnosis were retrospectively analysed. The children were divided into three groups according to BMI status at diagnosis: underweight, normal weight and overweight (BMIs <5%, 5%-85% and >85%, respectively). RESULTS: Of the 236 children [median age 7.87 (4.91-11) years] included in the study, 24 (10.1%) were underweight at diagnosis and 32 (13.6%) were overweight. Diarrhoea as the presenting symptom was significantly more common in the overweight group (p = 0.012), while short stature was more common in the underweight group (p = 0.002). Following a GFD had no significant effect on the children's BMI during a median follow-up of 15.7 (0-85) months, but there was a significant shift of patients between the BMI categories (p < 0.001). CONCLUSION: Although a shift of patients between the BMI categories was observed, following a GFD did not significantly affect the overall BMI in children with CD.

Age and pain score before gastrointestinal endoscopies in children are predictors for post procedure pain.

BACKGROUND: Gastrointestinal endoscopy may be associated with pain and anxiety. Predictors for high pain scores after endoscopies in children are not known. The aim of our study was to identify risk factors for prolonged recovery and higher pain scores after gastrointestinal endoscopy in children. METHODS: All the children that were electively admitted for gastrointestinal endoscopies were included. We retrospectively collected demographic, clinical and endoscopic data as well as information on the recovery process. A numerical rating scale and the Faces, Legs, Activity, Cry, and Consolability Scale were used for pain scoring. RESULTS: During the study period (01/2016-10/2016), 284 children (median age 10.7 years, interquartile range 6.7-14.8) were recruited. In a univariate analysis, older age, higher pre-procedure pain scores, longer procedure durations, higher number of biopsies and longer recovery duration were associated with higher post-procedure pain scores. In a multivariate analysis higher pain scores before the procedure (OR 12.42, 95% CI 3.67-42, P < 0.001) and older age (OR 1.016, 95% CI 1.007-1.025, P < 0.001) were associated with higher pain scores after the procedure. Children with a higher pain score before the procedure also had a longer recovery period (OR 5.28, 95% CI (1.93-14.49), P = 0.001). CONCLUSION: Older age and higher pain score before the procedure were identified as predictors for higher pain score after pediatric gastrointestinal endoscopies. Children with these risk factors should be identified before the procedure in order to personalize their post-procedure management.

Assessing the Validity of Adult-derived Prognostic Models for Primary Sclerosing Cholangitis Outcomes in Children.

BACKGROUND: Natural history models for primary sclerosing cholangitis (PSC) are derived from adult patient data, but have never been validated in children. It is unclear how accurate such models are for children with PSC. METHODS: We utilized the pediatric PSC consortium database to assess the Revised Mayo Clinic, Amsterdam-Oxford, and Boberg models. We calculated the risk stratum and predicted survival for each patient within each model using patient data at PSC diagnosis, and compared it with observed survival. We evaluated model fit using the c-statistic. RESULTS: Model fit was good at 1 year (c-statistics 0.93, 0.87, 0.82) and fair at 10 years (0.78, 0.75, 0.69) in the Mayo, Boberg, and Amsterdam-Oxford models, respectively. The Mayo model correctly classified most children as low risk, whereas the Amsterdam-Oxford model incorrectly classified most as high risk. All of the models underestimated survival of patients classified as high risk. Albumin, bilirubin, AST, and platelets were most associated with outcomes. Autoimmune hepatitis was more prevalent in higher risk groups, and over-weighting of AST in these patients accounted for the observed versus predicted survival discrepancy. CONCLUSIONS: All 3 models offered good short-term discrimination of outcomes but only fair long-term discrimination. None of the models account for the high prevalence of features of autoimmune hepatitis overlap in children and the associated elevated aminotransferases. A pediatric-specific model is needed. AST, bilirubin, albumin, and platelets will be important predictors, but must be weighted to account for the unique features of PSC in children.

Higher prevalence of obesity among children with functional abdominal pain disorders.

BACKGROUND: Functional abdominal pain (FAP) disorders are one of the most common gastrointestinal disorders in children. We aimed to define the association between obesity and functional abdominal pain (FAP) disorders and to assess differences between overweight/obese children and normal weight children with FAP disorders. METHODS: We conducted a retrospective study of children (2-18 years old) with a clinical diagnosis of FAP who were followed-up in our pediatric gastroenterology unit between 1/2016-10/2018. FAP disorders were defined according to the ROME IV criteria. Body mass index (BMI) percentiles were defined by CDC standards. Patients with BMIs ≥85th percentile were designated as being overweight/obese. A population control group was obtained from the 2015-2016 Israel national health survey. RESULTS: Data from 173 children with FAP disorders (median age 11.5 years, 114 females) were included. Seventy-one children (41%) were classified as having functional abdominal pain-NOS, 67 (38.7%) as having irritable bowel syndrome (IBS), and 35 (20.2%) has having functional dyspepsia. Fifty-three children (30.6%) were classified as being overweight/obese. Adolescents with FAP disorders had a significantly higher prevalence of overweight/obesity compared to controls (39.5% vs. 30%, respectively, p = 0.04). Children with FAP and overweight were older [12.4 (range 9.8-15.3) vs. 10.8 (7.4-14.1) years, p = 0.04] and had more hospitalizations due to FAP (20.8% vs. 7.6%, p = 0.01) compared to Children with FAP and normal weight. CONCLUSIONS: Adolescents with FAP had higher prevalence of overweight/obesity compared to controls. Future studies are warranted to raise awareness of weight issues in FAP and determine the effect of weight loss on FAP.

Ursodeoxycholic Acid Therapy in Pediatric Primary Sclerosing Cholangitis: Predictors of Gamma Glutamyltransferase Normalization and Favorable Clinical Course.

OBJECTIVE: To investigate patient factors predictive of gamma glutamyltransferase (GGT) normalization following ursodeoxycholic acid (UDCA) therapy in children with primary sclerosing cholangitis. STUDY DESIGN: We retrospectively reviewed patient records at 46 centers. We included patients with a baseline serum GGT level ≥50 IU/L at diagnosis of primary sclerosing cholangitis who initiated UDCA therapy within 1 month and continued therapy for at least 1 year. We defined "normalization" as a GGT level <50 IU/L without experiencing portal hypertensive or dominant stricture events, liver transplantation, or death during the first year. RESULTS: We identified 263 patients, median age 12.1 years at diagnosis, treated with UDCA at a median dose of 15 mg/kg/d. Normalization occurred in 46%. Patients with normalization had a lower prevalence of Crohn's disease, lower total bilirubin level, lower aspartate aminotransferase to platelet ratio index, greater platelet count, and greater serum albumin level at diagnosis. The 5-year survival with native liver was 99% in those patients who achieved normalization vs 77% in those who did not. CONCLUSIONS: Less than one-half of the patients treated with UDCA have a complete GGT normalization in the first year after diagnosis, but this subset of patients has a favorable 5-year outcome. Normalization is less likely in patients with a Crohn's disease phenotype or a laboratory profile suggestive of more advanced hepatobiliary fibrosis. Patients who do not achieve normalization could reasonably stop UDCA, as they are likely not receiving clinical benefit. Alternative treatments with improved efficacy are needed, particularly for patients with already-advanced disease.

Young Age Predicts Acute Pancreatitis Severity in Children.

OBJECTIVES: The course and evolution of pediatric acute pancreatitis (AP) is poorly understood. Prognostication models in children perform poorly and lack consensus. We aimed to identify predictors of AP severity, and the risk for AP recurrence. METHODS: We retrospectively studied all patients hospitalized with AP at a single tertiary center, between January 1995 and June 2016. Patient demographics and admission laboratory data were assessed for severity and recurrence prediction. RESULTS: A total of 68 patients accounting for a total of 117 (15 moderate-severe) AP episodes were reviewed. Patients with moderate-severe disease were significantly younger (median [interquartile range (IQR)] of 8.3 [4.0-14.4] vs 13.8 [8.1-16.0] years, P = 0.02). Young age at presentation was associated with odds ratio of 3.8 (confidence interval [CI] 1.2-12.1) for children younger than 12 years and 5.8 (CI 1.6-21.4) for children younger than 6 years for developing moderate-severe disease.Further subanalysis of the 59 patients with first-time AP episodes, demonstrated younger age (median [IQR] of 5.3 [2.9-10.4] vs 12.0 [6.3-15.8] years, P = 0.03) and elevated white blood cell count (median [IQR] of 22.8 [11.8-31.3] vs 11.0 [8.1-14.6] 10/L, P < 0.01) of patients with moderate-severe disease, conferring a risk for moderate-severe disease with odds ratio of 7.5 (CI 1.5-38.2) for children younger than 6 years and 5.3 (CI 1.1-25.4) for patients with white blood cell count >15 × 10/L, respectively. Fourteen (23.7%) of 59 patients with first-time episodes had recurrent AP. Analysis of the data at the primary episode failed to identify predictors to indicate future recurrence. CONCLUSIONS: In our cohort, only young age (<12 years) predicted AP severity. No parameters were identified to predict future development of AP recurrence.

Ultra-short Celiac Disease Is a Distinct and Milder Phenotype of the Disease in Children.

BACKGROUND AND AIMS: Approximately 10% of children with celiac disease (CD) have ultra-short celiac disease (USCD), where histological abnormalities are limited to the duodenal bulb. The aim of our retrospective study was to identify clinical and serological characteristics at baseline and at follow-up of children with USCD. METHODS: All children that were diagnosed with CD in our unit during 7/2010-12/2017, in whom biopsies were taken from duodenal bulb and second part, were included. We compared disease characteristics and course between children with USCD and children with involvement in the second part of the duodenum. RESULTS: Out of 3740 children who underwent upper gastrointestinal endoscopies, 648 were diagnosed with CD. Seventy-one (11%) of those children had limited involvement in the duodenal bulb. The USCD group included more females (P = 0.021), were older (P = 0.005), had a lower prevalence of diarrhea (P = 0.003), anemia (P = 0.007), anti-tissue transglutaminase (TTG) antibodies count (P < 0.001) at presentation, lower frequency of endoscopic abnormality, lower Marsh score, and a trend toward shorter time to the normalization of anti-TTG antibodies under a gluten-free diet compared to the extensive CD. There were no differences in body mass index or duration of symptoms before diagnosis. CONCLUSION: Children with USCD presented with a distinct phenotype of milder symptoms, lower celiac serology, and milder endoscopic and histological findings, with a trend toward faster normalization under a gluten-free diet compared to those with extensive CD. Further studies are needed to determine the long-term course and prognosis of USCD.

De Novo Allergy and Immune-Mediated Disorders Following Solid-Organ Transplantation-Prevalence, Natural History, and Risk Factors.

OBJECTIVES: To describe the prevalence, natural course, outcome, and risk factors of post-transplant de novo allergy and autoimmunity. STUDY DESIGN: A cross-sectional, cohort study of all children (<18 years) who underwent a solid-organ transplantation, between 2000 and 2012, in a single transplant center, with a follow-up period of 6 months or more post-transplant and without history of allergy or immune-mediated disorder pretransplant. RESULTS: A total of 626 eligible patients were screened, and 273 patients (160 males; 59%) met the inclusion criteria; this included 111 liver, 103 heart, 52 kidney, and 7 multivisceral recipients. Patients were followed for a median period of 3.6 years. A total of 92 (34%) patients (42 males, 46%) developed allergy or autoimmune disease after transplantation, with a high prevalence among liver (41%), heart (40%), and multivisceral (57%) transplant recipients compared with kidney recipients (4%; P < .001). Post-transplant allergies included eczema (n = 44), food allergy (22), eosinophilic gastrointestinal disease (11), and asthma (28). Autoimmunity occurred in 18 (6.6%) patients, presenting mainly as autoimmune cytopenia (n = 10). In a multivariate analysis, female sex, young age at transplantation, family history of allergy, Epstein-Barr virus infection, and elevated eosinophil count >6 months post-transplantation were associated with an increased risk for allergy or autoimmunity. Two patients (0.7%) died from autoimmune hemolytic anemia and hemophagocytic lymphohistiocytosis, and 52 episodes of post-transplant allergy, autoimmunity, and immune-mediated disorders (37%) did not improve over time. CONCLUSIONS: Allergy and autoimmunity are common in pediatric liver, heart, and multivisceral transplant recipients and pose a significant health burden. Further studies are required to clarify the mechanisms behind this post-transplant immune dysregulation.

The natural history of primary sclerosing cholangitis in 781 children: A multicenter, international collaboration.

There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes. (Hepatology 2017;66:518-527).