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Portal cavernoma cholangiopathy refers to changes in the intrahepatic and extrahepatic biliary ducts in patients with extrahepatic portal venous obstruction. Spontaneous hemobilia in the setting of portal cavernoma cholangiopathy is extremely rare, and it poses diagnostic as well as therapeutic challenge. Here, we report the case of a 10-year-old girl with extrahepatic portal venous obstruction, who presented with hemobilia. Computed tomography angiography of abdomen and endoscopic ultrasound confirmed the presence of pericholedochal, paracholedochal, and intracholedochal varices. Hemostasis was achieved with the placement of a fully covered self-expanding metallic stent into the common bile duct. Fully covered self-expanding metallic stent is safe and effective for control of bleeding in children presenting with hemobilia.
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Significance of autoantibodies in pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. Our aim was to determine the prevalence and significance of autoantibodies in MASLD. PubMed and Scopus were searched and six articles (689 [487 males] MASLD patients) were identified. Antinuclear antibodies (ANA) was positive in 28% (95% confidence interval [CI]: 17%-39%, n = 6 studies), Antismooth muscle antibodies (ASMA) in 28% (95% CI: 8%-50%, n = 5 studies), Actin-positive in 15% (95% CI: 10%-20%, n = 2 studies) and elevated immunoglobulin G in 17% (95% CI: 1%-39%, n = 4 studies). Anti-liver-kidney-microsomal antibody was not present in any patient. There was no significant association of ANA positivity with degree of liver steatosis, liver fibrosis or nonalcoholic fatty liver disease activity score (NAS) but patients with ASMA positivity had advanced fibrosis (pooled risk ratio [RR] 1.77; 95% CI 1.16-2.71) and higher risk of NAS ≥5 (pooled RR 1.21; 95% CI: 1.01-1.44, n = 2 studies, 243 patients). To conclude, non-organ specific autoantibodies are present in over one-fourth of children with MASLD and the presence of ASMA maybe associated with increased disease severity.
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Objective: Hepatic encephalopathy (HE) is a marker of poor prognosis in adults with chronic liver disease (CLD). We prospectively studied the prevalence and precipitants of HE in children with CLD as there is a paucity of literature on the same. Methods: Children (1-18 years) admitted with CLD were examined daily for the presence and grading of HE (West Haven/Whittington grading). Precipitants were classified as infection, dyselectrolytemia, gastrointestinal bleeding, constipation and dehydration. Changes in grades of HE and outcome were noted. Results: One hundred and sixty children (age 120 [84-168] months) were enrolled. HE was present in 50 (31.2%) patients with a total of 61 episodes. Maximum grade of HE was grade I (n = 16), II (n = 23), III (n = 11) and IV (n = 11). Forty-two cases had single and 8 had recurrent (2-5) episodes. Median duration of HE episodes was 96 (72-192) hours. Precipitants were identified in 55/61 (90.2%) episodes with infection (45/61, 73.7%) and dyselectrolytemia (33/61, 54%) being the most common. Lower albumin and sodium, higher INR and presence of infection were significantly associated with presence of HE. Overall, HE resolved in 33 (54%) episodes, while it progressed and persisted in 28 (45.9%) episodes. Patients with HE had a poorer outcome (25/50 vs 13/110; P < 0.01) with both higher in-hospital (11/50 vs 9/110; P = 0.02) and 1-month post discharge (14/39 vs 4/101; P < 0.01) mortality than those without HE. Conclusion: One-third of admitted CLD children have HE, with identifiable precipitants in 90% of cases. Children with HE have poorer liver functions, higher rate of infections and worse outcome than those without HE.
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OBJECTIVE: Biomarkers with high accuracy for identification of infection in decompensated chronic liver disease (DCLD) are urgently needed. We compared the accuracy of neutrophilic cluster of differentiation 64 (nCD64) with procalcitonin for diagnosis of bacterial infection in children with DCLD. METHODS: Consecutive children admitted with DCLD were enrolled prospectively. nCD64 was assessed by flow cytometry and expressed in percentage. nCD64, procalcitonin and hemogram were measured at admission and 7-14 days after treatment in those with infection. Complete work-up for infection was done. Presence, site and severity of infection was classified as per guidelines. RESULTS: 107 children [64 boys, age 97(18-168) months] were enrolled. 78(72.9%) had infection, 26(24%) had severe sepsis and 60(56%) had systemic inflammatory response syndrome. The commonest site of infection was ascitic fluid (n=37), followed by pneumonia (n=24), urinary tract (n=15), bacteraemia (n=10), cholangitis (n=8) and cellulitis (n=3). nCD64 (cut-off-51%, AUC-0.82) had a higher sensitivity (79.5%) and specificity (82.8%) than procalcitonin (cut-off ≥0.58ng/mL, AUC-0.74, sensitivity-76.9% and specificity-62.1%) for diagnosis of infection. nCD64 and procalcitonin correlated with infection severity, being highest in children with severe sepsis [88(71-97) %and 1.98(0.83-10.36) ng/mL], than in infection alone [72(45-84) % and 1.09(0.45-2.07) ng/mL], and no-infection [36(20.2-48) % and 0.42(0.19-1.08) ng/mL]. There was no difference in diagnostic utility of procalcitonin or nCD64 with different sites of infection. Elevation of all 3 parameters (nCD64, PCT and total leukocyte count) was uncommon but highly specific for presence of infection. CONCLUSION: nCD64 identifies infection better than procalcitonin and correlates well with infection severity in children with DCLD.
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INTRODUCTION: Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare entity that mimics various inflammatory strictures of the small intestine. Pediatric literature is scarce. We analyzed the clinical, radiological, endoscopic and histopathological features of children with CMUSE that differentiate it from small bowel Crohn's disease (SBCD) and gastrointestinal tuberculosis (GITB). METHODS: CMUSE was diagnosed by the following criteria: (1) unexplained small bowel strictures with superficial ulcers, (2) chronic/relapsing ulcers of small bowel after resection, (3) no signs of systemic inflammation, (4) absence of other known etiologies of small bowel ulcers. SBCD and GITB were diagnosed based on standard criteria. The clinical features, laboratory parameters, radioimaging, endoscopy (including video capsule endoscopy [VCE], intra-operative endoscopy), histopathological features and treatment outcome were noted. RESULTS: Out of 48, CMUSE was diagnosed in 13 (27%) isolated small bowel and ileocecal strictures, while GITB and SBCD accounted for 41% and 21% cases, respectively. Common presentations were sub-acute obstruction (46%), obscure gastrointestinal bleeding (38%) and protein-losing enteropathy (38%). CMUSE patients had significantly longer disease duration compared to SBCD and GITB (p < 0.001). SBCD (90.0%) and GITB (85%) cases had elevated C-reactive protein (CRP), none with CMUSE had elevated CRP (p < 0.001). The disease was localized in jejunum (100%) and proximal ileum (56%) in CMUSE, ileocecal region (85%) in GITB, but evenly distributed in small intestine in SBCD. Endoscopy showed evenly placed, superficial, circumferential ulcers with strictures in CMUSE, deep linear ulcers in SBCD and circumferential ulcers in GITB. Upfront immunosuppression was given in four; three (75%) of them relapsed. Only surgery was done in three with one (25%) having relapse. Upfront surgery followed by immunosuppression was used in six, but all relapsed and two required repeat surgery. CONCLUSION: CMUSE is important but underdiagnosed in children. Lack of constitutional symptoms, normal inflammatory parameters and characteristic ulcers with strictures helped in differentiating CMUSE from GITB and SBCD.
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BACKGROUND AND OBJECTIVES: The impact of chronic pancreatitis (CP) on quality of life (QOL) of children is not well established. Our objective was to evaluate the QOL, identify contributing factors, and determine the prevalence of anxiety and depression in children with CP in India. METHODS: Children (8-18y old) with CP were prospectively enrolled across three pediatric gastroenterology centres in India. QOL was assessed using the pediatric QOL inventory (PedsQL 4.0) scale, administered to both children and their parents. Anxiety and depression was studied using the Revised Children's Anxiety and Depression Scale (RCADS 25). Contributing factors were identified using binary logistic regression analysis. The data was compared against published QOL data in healthy Indian children. RESULTS: 121 children with CP (boys-57.9 %, age at QOL-14 ± 3.2years) were enrolled. A majority (82.7 %) had pain and advanced disease (Cambridge grade IV- 63.6 %). Children with CP had poorer QOL compared to controls (total score 74.6 ± 16 vs. 87.5 ± 11.1, p < 0.0001). QOL scores were similar across centres. Older children were similar to younger ones, except for a poorer emotional QOL. Taking QOL < -2 standard deviation (SD) of controls, â¼35 % had poor physical (50.9 ± 11.9) and 20 % had poor psychosocial (PS) QOL score (52.1 ± 7.2). On analysis, presence of pain and lower socio-economic status (SES) adversely affected both physical and PS-QOL. Additionally, girls had poorer PS-QOL than boys (Odds ratio 3.1, 95%CI:1.23-7.31). Anxiety and depression were uncommon (2,1.6 %). CONCLUSIONS: Patients with CP had impaired physical and psycho-social QOL. Presence of pain and lower SES adversely affected QOL. Psychiatric comorbidities were uncommon.
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Introduction Pancreatic fluid collection (PFC) is one of the most frequent complications associated with acute pancreatitis. The route of drainage is guided by the size and site of collection. The present study aims to assess the clinical and technical success of transgastric percutaneous drainage (PCD) for managing retrogastric walled-off pancreatic necrosis (WOPN). Materials and methods A total of 44 patients with acute pancreatitis diagnosed with WOPN who underwent transgastric PCD with ultrasound or CT guidance as part of standard clinical management were included in the study. Patients were observed for improvement in clinical parameters, and treatment outcomes were noted in terms of technical success, clinical success, adverse events, need for additional procedures, hospital stay, and duration of placement of all drains. Data for the internalization of transgastric PCD was also observed in the study. Results Technical success during the drain placement was observed in 93% (n=41) of patients.Internalization of the transgastric drain was attempted in 12 patients and successful in 11 (91%). The median duration of hospital stay from the time of placement of the first PCD until discharge and the median duration of all PCDs placed were higher in patients where the transgastric drain was not internalized as compared to patients where the transgastric drain was internalized. Conclusion In WOPN, transgastric drain placement and successful internalization in any form help in the early resolution of peripancreatic and abdominal collections. It also reduces the time to percutaneous catheter removal, which in turn reduces the morbidity and decreases the need for additional interventions or surgery.
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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in children and adolescents, particularly those with obesity. NAFLD is considered a hepatic manifestation of the metabolic syndrome due to its close associations with abdominal obesity, insulin resistance, and atherogenic dyslipidemia. Experts have proposed an alternative terminology, metabolic dysfunction-associated fatty liver disease (MAFLD), to better reflect its pathophysiology. This study aimed to develop consensus statements and recommendations for pediatric MAFLD through collaboration among international experts. METHODS: A group of 65 experts from 35 countries and six continents, including pediatricians, hepatologists, and endocrinologists, participated in a consensus development process. The process encompassed various aspects of pediatric MAFLD, including epidemiology, mechanisms, screening, and management. FINDINGS: In round 1, we received 65 surveys from 35 countries and analyzed these results, which informed us that 73.3% of respondents agreed with 20 draft statements while 23.8% agreed somewhat. The mean percentage of agreement or somewhat agreement increased to 80.85% and 15.75%, respectively, in round 2. The final statements covered a wide range of topics related to epidemiology, pathophysiology, and strategies for screening and managing pediatric MAFLD. CONCLUSIONS: The consensus statements and recommendations developed by an international expert panel serve to optimize clinical outcomes and improve the quality of life for children and adolescents with MAFLD. These findings emphasize the need for standardized approaches in diagnosing and treating pediatric MAFLD. FUNDING: This work was funded by the National Natural Science Foundation of China (82070588, 82370577), the National Key R&D Program of China (2023YFA1800801), National High Level Hospital Clinical Research Funding (2022-PUMCH-C-014), the Wuxi Taihu Talent Plan (DJTD202106), and the Medical Key Discipline Program of Wuxi Health Commission (ZDXK2021007).
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Consenso , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Criança , Adolescente , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/terapia , Síndrome Metabólica/metabolismoRESUMO
Cholestatic liver diseases in children often have an underlying genetic defect. Genetic testing by next-generation sequencing has become a crucial part of the diagnostic armamentarium in such clinical scenarios. Here, we report three children who presented with early-onset cholestatic jaundice and pruritus. All of them had low gamma-glutamyl transferase and high serum bile acid levels. Symptoms were alleviated with ursodeoxycholic acid and cholestyramine in all 3 children with normal LFT at follow-up. They were detected to have novel pathogenic USP53 mutations (2 homozygous, 1 compound heterozygous) on next-generation sequencing which have previously not been reported.
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BACKGROUND: Ascites in children is multifactorial and serum ascites albumin gradient (SAAG) ≥1.1 helps differentiate portal hypertension (PHTN) related from non-PHTN ascites. AIMS: We evaluated the aetiology and diagnostic accuracy of SAAG in children with ascites. METHODS: Children with ascites were retrospectively evaluated. Etiological diagnosis was based on clinical presentation and investigations. All cases with ascitic fluid analysis and a definite diagnosis were included for calculating the utility of SAAG. RESULTS: We enrolled 878 children (568[64.7%] boys). Majority were PHTN related (638[72.7%]) and secondary to acute viral hepatitis (98,15.4%), acute liver failure (185,29%), chronic liver disease (276,43.3%) and Budd-Chiari syndrome (79,12.4%). Other causes included tubercular (46,5.2%), pancreatic (32,3.6%), chylous (20,2.3%), biliary (12,1.4%), pseudoascites (16,1.8%), infections (46,5.2%), nephrotic (26,2.9%), malignancy (23,2.6%), cardiac (9,1.0%) and others (10,1%). SAAG (n = 305) correctly differentiated PHTN and non-PHTN ascites in 272 (89.2%) cases, with a high sensitivity (97%), specificity (93%) and diagnostic accuracy (95.8%). Reasons for inaccurate SAAG included mixed ascites (n = 9), different day serum and ascitic fluid albumin estimation (n = 5), serum albumin ≤1.1 g/dL (n = 2), chylous ascites (n = 3), hypergammaglobulinemia (n = 1), albumin infusions (n = 1) and unexplained (n = 12). CONCLUSIONS: Nearly 27% children had non-PHTN related ascites. SAAG differentiates PHTN from non-PHTN ascites with a diagnostic accuracy of 95%.
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BACKGROUND: Acute hepatitis due to various tropical infections can mimic the clinical picture of acute viral hepatitis(AVH), leading to increased morbidity and mortality. We aimed to identify clinical and laboratory parameters that could help to distinguish acute hepatitis due to tropical infections from AVH. METHODS: We retrospectively analyzed our database of 150 children (107 boys) with AVH and 50 children(34 boys)with acute hepatitis due to tropical infections between January 2013 and March 2023. Clinical features, investigations, complications and outcomes were compared. RESULTS: Hepatitis A (75%) was the commonest etiology of AVH while enteric fever (34%), dengue (26%), scrub typhus (20%) and leptospirosis (16%) constituted the majority of tropical infections. Persistent fever and skin rashes were found in 88% and 16% of patients respectively in the tropical infection group and none in the AVH group (p < 0.001). On univariate analysis, prodromal symptoms, clinically detectable jaundice, cholestatic pattern, total and direct bilirubin and liver enzymes were significantly higher in AVH while headache, myalgia, leukopoenia, thrombocytopenia, hyponatremia were significantly higher in tropical infections group (all p < 0.05). Multivariate analysis identified thrombocytopenia (Odds ratio [OR] 4.237) as an independent positive predictive factor and markedly elevated total bilirubin (OR 0.575), direct bilirubin (OR 0.498), aspartate aminotransferase (OR 0.841) and alanine aminotransferase (OR 0.863) as independent negative predictive factors for acute hepatitis due to tropical infections. CONCLUSION: High index of suspicion for tropical infections is warranted in patients with persistent fever after the onset of jaundice, especially in the presence of skin rash and thrombocytopenia.SUMMARYAcute viral hepatitis and acute hepatitis due to tropical infections can have similar clinical and biochemical parameters. Milder degree of jaundice, lower elevation of serum transaminases and thrombocytopenia can be useful predictors for acute hepatitis due to tropical infections.
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Idiopathic pulmonary fibrosis (IPF) is a continuous, progressive, and lethal age-related respiratory disease. It is characterized by condensed and rigid lung tissue, which leads to a decline in the normal functioning of the lungs. The pathophysiology of IPF has still not been completely elucidated, so current strategies are lagging behind with respect to improving the condition of patients with IPF and increasing their survival rate. The desire for a better understanding of the pathobiology of IPF and its early detection has led to the identification of various biomarkers associated with IPF. The use of drugs such as pirfenidone and nintedanib as a safe and effective treatment alternative have marked a new chapter in the treatment of IPF. However, nonpharmacological therapies, involving long-term oxygen therapy, transplantation of the lungs, pulmonary rehabilitation, ventilation, and palliative care for cough and dyspnea, are still considered to be beneficial as supplementary methods for IPF therapy. A major risk factor for IPF is aging, with associated hallmarks such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis, and mitochondrial dysfunction. These are promising earmarks for the development of potential therapy for the disease. In this review, we have discussed current and emerging novel therapeutic strategies for IPF, especially for targets associated with age-related mechanisms.
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Fibrose Pulmonar Idiopática , Humanos , Fibrose Pulmonar Idiopática/terapia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/fisiopatologia , Indóis/uso terapêutico , Animais , Piridonas/uso terapêutico , Envelhecimento/fisiologiaAssuntos
Hepatopatias , Transplante de Fígado , Criança , Humanos , Lactente , Hepatopatias/diagnóstico , Hepatopatias/cirurgia , Doença CrônicaRESUMO
BACKGROUND: Post-endoscopic retrograde cholangio-pancreatography pancreatitis (PEP) is seen in 3% to 16% of children undergoing therapeutic endoscopic retrograde cholangio-pancreatography (ERCP). We evaluated the risk factors of PEP and utility of 4-hour post-ERCP amylase and lipase for early prediction of PEP in children with chronic pancreatitis (CP). MATERIALS AND METHODS: Thirty children with CP (boys 20, 14.3 [interquartile range, 9.3-16] years) who underwent 62 ERCP procedures were studied. Clinical and procedural details with outcome were noted. Serum amylase and lipase were measured before, 4 hours, and 24 hours after ERCP. Multivariate analysis was done to identify risk factors for PEP. Cutoff scores of 4-hour amylase and lipase were identified. RESULTS: PEP occurred in 14.5% (9/62) of ERCP procedures (mild, 8; moderate, 1) with no mortality. On univariate analysis, endoscopic sphincterotomy ( P = 0.04), difficult cannulation ( P = 0.004), and prior PEP ( P = 0.036) were risk factors, while prior ERCP ( P = 0.04) was protective. Difficult cannulation (odds ratio, 5.83; 95% confidence interval, 1.329-25.592) was the independent risk factor on multivariate analysis overall and for first ERCP session alone. Amylase >3.3 times upper limit of normal (ULN) and lipase of >5 times ULN at 4 hours had best sensitivity and specificity for diagnosis of PEP. All cases with PEP were symptomatic by 6 hours and none had amylase/lipase <3 ULN at 4 hours. Amylase/lipase of <3 ULN at 4 hours could exclude PEP with good sensitivity (100%) and specificity (76% and 81%, respectively). CONCLUSIONS: PEP occurred in 14.5% of procedures in children with CP, with difficult cannulation being the independent risk factor. Asymptomatic patients with 4-hour amylase/lipase <3 times ULN can be safely discharged.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatite Crônica , Masculino , Criança , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Lipase , Fatores de Risco , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/cirurgia , Pancreatite Crônica/etiologia , AmilasesRESUMO
OBJECTIVES: Radiological intervention (RI) is the preferred treatment in children with Budd-Chiari syndrome (BCS). We studied the comparative long-term outcome of BCS children, with and without RI and utility of liver and splenic stiffness measurement (LSM, SSM) by 2-dimensional shear wave elastography (2D-SWE) in assessing response. METHODS: Sixty children (40 boys, median age 10.5 [6.5-15.25] years) with BCS (29 newly diagnosed, 31 follow-up) were evaluated. LSM and SSM by 2D-SWE and vascular patency were monitored pre- and postprocedure (≥ 6 months postprocedure) in those undergoing RI. Medical therapy without anticoagulation and monitoring was done in subjects without RI. The RI and no-RI groups were compared. RESULTS: Ascites (54,90%), hepatomegaly (56,93%) and prominent abdominal-veins (42,70%), were the commonest features. The majority (46,78%) had isolated hepatic vein block. 44 (73%) cases underwent RI, while 16 (27%) were managed conservatively. Both groups were similar at baseline. Post-RI subjects showed significant improvement in clinical findings, liver functions and portal hypertension. LSM [33 (32-34.5) to 19.2 (18-20.67) kPa] and SSM [54.5 (52.3-57.6) to 28.9 (27.6-30.25) kPa] showed a significant decline from baseline value over a follow-up of 12 (6-13) months. Gradual reduction occurred in the LSM and SSM over 1-5 years, with near-normal LSM [10.2 (9.2-11.5) kPa] and SSM [22.3 (20.5-24.3) kPa] values in patients (n-16) with > 5 years follow-up. Patients without RI showed worsening in LSM and SSM. Hepatopulmonary syndrome and hepatocellular carcinoma developed in 4 (8%) and 1 (1.7%) cases respectively. CONCLUSION: RI leads to clinical recovery and reduction with near normalization of LSM and SSM over long-term follow-up in children with BCS. 2D-SWE is a promising tool to monitor outcomes.
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Síndrome de Budd-Chiari , Técnicas de Imagem por Elasticidade , Hipertensão Portal , Neoplasias Hepáticas , Masculino , Criança , Humanos , Síndrome de Budd-Chiari/diagnóstico por imagem , Síndrome de Budd-Chiari/terapia , Técnicas de Imagem por Elasticidade/métodos , Fígado/patologia , Hipertensão Portal/patologia , Neoplasias Hepáticas/patologia , Cirrose Hepática/patologiaRESUMO
Background and Aim: The prevalence of eosinophilic esophagitis (EoE) is rising in the West. However, data from the Indian subcontinent is limited. In this prospective cross-sectional study, we estimated the prevalence of EoE among children undergoing elective upper gastrointestinal endoscopy (UGIE). Methods: We enrolled 200 consecutive children (123 boys, median age 10.25 years [interquartile range 8.25-14.5]) between March 2020 and November 2022 at our center. Clinical characteristics, endoscopic findings, and laboratory parameters were noted. A total of 12 mucosal biopsies (3 each from the middle and lower third of the esophagus, stomach, and duodenum) were obtained. EoE was diagnosed if the peak eosinophil count was ≥15/high-power field (HPF) in absence of gastric and duodenal eosinophilia. Results: The commonest indications for UGIE were gastroesophageal reflux disease-like symptoms (29%), inflammatory bowel disease (22.5%), celiac disease (15%), and abdominal pain (13%). EoE was detected in seven children, suggesting an overall prevalence of 3.5%. Of the 20 children evaluated for dysphagia, 4 (20%) had EoE. Also, two of three (67%) children presented with food bolus impaction along with dysphagia had EoE. Of the seven children with EoE, three (43%) had bronchial asthma, two (28.5%) had peripheral eosinophilia, and one (14%) had elevated serum IgE. Trachealization and linear furrows were found in 57% and 71% cases, respectively. Four children received high-dose proton pump inhibitor (PPI) for 12 weeks, two received PPI+ stricture dilatation, and one received systemic steroids. All achieved clinical, endoscopic, and histopathological remission. Conclusion: Hospital-based prevalence of EoE among children undergoing elective UGIE was 3.5%. EoE patients had favorable outcomes with PPI.