Discrimination of pediatric cryptogenic multifocal ulcerous stenosing enteritis from small bowel Crohn's disease and gastrointestinal tuberculosis: A retrospective study (with videos).

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.

Fecal microbiota transplantation in the treatment of hepatic encephalopathy: A perspective.

Due to its complex pathogenesis, treatment of hepatic encephalopathy (HE) continues to be a therapeutic challenge. Of late, gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use. New evidence suggests that gut microbiota plays a significant role in cerebral homeostasis. Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies. Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics, prebiotics and the latest fecal microbiota transplantation (FMT). Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE. However, questions over the appropriate dose, duration and route of administration for best treatment outcome remains unsettled.

Hepatic pseudotumor: A diagnostic challenge.

Hepatic pseudotumors are rare lesions of unknown origin, characterized by the proliferation of fibrous connective tissue and inflammatory cell infiltrates. They mimic malignant lesions clinically, and radiologically, given their non-specific clinical and imaging features. The pathophysiology of hepatic pseudotumor is incompletely understood and there are no standardized criteria for diagnosis. Pseudotumors have been reported to develop in various organs in the body with the lung and liver being the most common site. Hepatic pseudotumors develop in patients with underlying triggers of liver inflammation and injury, including infections, autoimmune liver diseases, bile duct injury, or surgery. Hepatic pseudotumors respond well to conservative treatment with antibiotics, and steroids and some may regress spontaneously, thus avoiding unnecessary resection. This condition is rewarding to treat. It is important to recognize pseudotumor as a distinct clinical entity and include it in the differential of liver masses with atypical imaging features.

Metabolic dysfunction-associated steatotic liver disease: A silent pandemic.

The worldwide epidemiology of non-alcoholic fatty liver disease (NAFLD) is showing an upward trend, parallel to the rising trend of metabolic syndrome, owing to lifestyle changes. The pathogenesis of NAFLD has not been fully understood yet. Therefore, NAFLD has emerged as a public health concern in the field of hepatology and metabolisms worldwide. Recent changes in the nomenclature from NAFLD to metabolic dysfunction-associated steatotic liver disease have brought a positive outlook changes in the understanding of the disease process and doctor-patient communication. Lifestyle changes are the main treatment modality. Recently, clinical trial using drugs that target 'insulin resistance' which is the driving force behind NAFLD, have shown promising results. Further translational research is needed to better understand the underlying pathophysiological mechanism of NAFLD which may open newer avenues of therapeutic targets. The role of gut dysbiosis in etiopathogenesis and use of fecal microbiota modification in the treatment should be studied extensively. Prevention of this silent epidemic by spreading awareness and early intervention should be our priority.

Pediatric acute liver failure: Current perspective in etiology and management.

Pediatric acute liver failure (PALF) is a catastrophic clinical condition with very high morbidity and mortality without early detection and intervention. It is characterized by the acute onset of massive hepatocellular injury that releases circulating inflammatory mediators, resulting in metabolic disturbances, coagulopathy, hepatic encephalopathy and multi-organ failure. The etiological spectrum is dominated by hepatotropic viruses, drug-induced liver injury, metabolic and genetic disorders and immune-mediated diseases. Unlike adults, indeterminate causes for acute liver failure constitute a considerable proportion of cases of acute liver failure in children in the west. The heterogeneity of age and etiology in PALF has led to difficulties in developing prognostic scoring. The recent guidelines emphasize prompt identification of PALF, age-appropriate evaluation for hepatic encephalopathy and laboratory evaluation with careful monitoring. Current therapy focuses on supporting the failing liver and other organs, pending either spontaneous recovery or liver transplantation. Targeted therapy is available for a select group of etiologies. Liver transplantation can be lifesaving and a plan for the same should be organized, whenever indicated. The aim of this review is to define PALF, understand its etiopathogenesis, address the challenges encountered during the management and update the latest advances in liver transplantation and non-transplant treatment options in PALF.

Cholestatic Liver Disease due to Novel USP53 Mutations: A Case Series of Three Indian Children.

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.

Persistent fever in acute hepatitis: think beyond acute viral hepatitis.

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.

Risk Factors for Post-Endoscopic Retrograde Cholangio-Pancreatography Pancreatitis in Children With Chronic Pancreatitis and Its Prediction Using 4-Hour Postprocedure Serum Amylase and Lipase Levels.

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.

Eosinophilic esophagitis in children: A cross-sectional study from a tertiary care center.

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.

Budd-Chiari syndrome in children: Radiological intervention and role of shear wave elastography in monitoring response.

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.

Budd-Chiari syndrome in children: Challenges and outcome.

Budd-Chiari syndrome (BCS) is an uncommon disease of the liver, characterised by obstruction of the hepatic venous outflow tract. The etiological spectrum of BCS as well as venous obstruction pattern show wide geographical and demographic variations across the globe. Compared to adults with BCS, children have primary BCS as the predominant etiology, earlier clinical presentation, and hence better treatment outcome. Underlying prothrombotic conditions play a key role in the etiopathogenesis of BCS, though work-up for the same is often unyielding in children. Use of next-generation sequencing in addition to conventional tests for thrombophilia leads to better diagnostic yield. In recent years, advances in radiological endovascular intervention techniques have revolutionized the treatment and outcome of BCS. Various non-invasive markers of fibrosis like liver and splenic stiffness measurement are being increasingly used to assess treatment response. Elastography techniques provide a novel non-invasive tool for measuring liver and splenic stiffness. This article reviews the diagnostic and therapeutic advances and challenges in children with BCS.

Challenges and dilemmas in pediatric hepatic Wilson's disease.

Wilson disease is an autosomal recessive disorder affecting the ATP7B gene located on chromosome 13q. This leads to copper deposition in various organs, most importantly in the liver and brain. The genetic mutations are vast, well reported in the West but poorly documented in developing countries. Hence the diagnosis is made with a constellation of clinico-laboratory parameters which have significant overlap with other liver diseases and often pose a significant dilemma for clinicians. Diagnostic scoring systems are not fool-proof. The availability and affordability of chelators in developing countries impact the drug compliance of patients. While D-penicillamine is a potent drug, its side effects lead to drug discontinuation. Trientine is cost-prohibitive in developing countries. There is no single test to assess the adequacy of chelation. Exchangeable urinary copper is an essential upcoming diagnostic and prognostic tool. In the presence of cirrhosis, hypersplenism clouds the assessment of myelosuppression of drugs. Similarly, it may be difficult to distinguish disease tubulopathy from drug-induced glomerulonephritis. Neurological worsening due to chelators may appear similar to disease progression. Presentation as fulminant hepatic failure requires rapid workup. There is a limited window of opportunity to salvage these patients with the help of plasmapheresis and other liver-assisted devices. This review addresses the challenges and clinical dilemmas faced at beside in developing countries.

Cholestatic Liver Disease in a Child with KIF12 Mutation.

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, authors report an infant with recurrent cholestasis, pruritus, elevated gamma-glutamyl transpeptidase, patent biliary tract and biliary changes on histology who was detected to have a novel KIF12 mutation, which is crucial for intracellular transport of microtubules and cellular polarity in hepatocytes. The child developed progressive liver dysfunction and decompensation in the form of ascites and coagulopathy over a span of eight years. This case highlights the role of next-generation sequencing in identifying novel mutations, which can help in both diagnosis and prognostication.

Endoscopic Band Ligation in Blue Rubber Bleb Nevus Syndrome: A Report of Two Children.

Blue rubber bleb nevus syndrome (BRBNS) is a rare congenital disorder presenting with multifocal venous malformations of the skin, soft tissues, and gastrointestinal (GI) tract. Patients usually present with chronic anemia resulting from occult GI bleeding and sometimes with massive GI bleeding. We report 2 children with blue rubber bleb nevus syndrome with GI bleeding: 1 with obscure GI bleeding and the other with overt GI bleeding. In both cases, the presence of cutaneous lesions provided useful clues toward diagnosis. Colonoscopy and upper GI endoscopy revealed bluish polypoidal lesions in the GI tract. Capsule endoscopy helped in disease mapping. Both of them were successfully treated with endoscopic band ligation and nonselective beta-blockers, which resulted in an improvement in their hemoglobin levels. Our cases highlight the successful use of endoscopic band ligation of GI lesions as a therapeutic modality. It is important for gastroenterologists to be aware of this rare condition for current diagnosis.

How to suspect the presence of high-risk esophageal varices and when to start endoscopic surveillance in children with biliary atresia?

BACKGROUND AND AIM: Portal hypertension determines the outcome of children with biliary atresia (BA) and is common even after a successful Kasai portoenterostomy (KPE). However, there are no clear-cut guidelines on the age of starting surveillance and the modality (endoscopy vs non-invasive tests [NITs]). In this cohort study, we analyzed our database to find out the utility of NITs in detecting high-risk esophageal varices in BA. METHODS: From June 2010 to May 2022, consecutive children of BA who underwent upper gastrointestinal (UGI) endoscopy were included. Esophageal varices were classified as high-risk (grade II with red-color signs or grade III or IV irrespective of red-color signs. NITs such as splenomegaly (clinical and USG), platelet count, aspartate transaminase to platelet ratio index (APRI), and platelet-to-spleen diameter ratio were compared between cases with high-risk and low-risk varices. RESULTS: A total of 110 children, 75 boys (66 successful KPE and 44 failed/KPE not performed) were enrolled. The median age at KPE was 85 days (IQR 63-98). Thirteen (11.8%) children presented with UGI bleeding. The first endoscopy revealed gastroesophageal varices in 75.4% of cases, and 32% of them had high-risk varices. Multivariate analysis revealed failed KPE, history of UGI bleeding, bigger spleen size (> 3.5 cm), lower platelet count (< 150 000), and higher APRI (> 2) are independent predictors of the presence of high-risk esophageal varices. CONCLUSION: Endoscopy is the best in predicting the presence of high-risk varices that might bleed; hence, early surveillance endoscopy should be started in children with splenomegaly, thrombocytopenia, and high APRI score to prevent variceal bleeding.

Modal and nonmodal stability analysis for an electrified falling film.

We have performed the modal and nonmodal stability analyses of a gravity-driven three-dimensional viscous incompressible fluid flowing over an inclined plane in the presence of a uniform electric field acting normal to the plane at infinity. The time evolution equations are derived for normal velocity, normal vorticity, and fluid surface deformation, respectively, and solved numerically by using the Chebyshev spectral collocation method. The modal stability analysis demonstrates the existence of three unstable regions for the surface mode in the wave number plane at the lower value of the electric Weber number. However, these unstable regions coalesce and magnify as the electric Weber number rises. By contrast, there exists only one unstable region for the shear mode in the wave number plane, which attenuates slightly with an increase in the value of the electric Weber number. But both the surface and shear modes are stabilized in the presence of the spanwise wave number, where the long-wave instability shifts towards the finite wavelength instability as the spanwise wave number rises. On the other hand, the nonmodal stability analysis reveals the existence of transient disturbance energy growth, the maximum value of which intensifies slightly with an increase in the value of the electric Weber number.

MPV17 mutation-related mitochondrial DNA depletion syndrome: A case series in infants.

MPV17 is a mitochondrial inner membrane protein, involved in transporting deoxynucleotides into the mitochondria. Pathogenic MPV17 mutations can cause mitochondrial deoxyribonucleic acid (DNA) depletion syndrome, which has a varied presentation with neurological, muscular and hepatic involvement. Presentation as liver failure is relatively uncommon. Here, we report four infants from four separate families with pathogenic, homozygous MPV17 mutations. All had predominant hepatic involvement with cholestasis, lactic acidosis and hypoketotic hypoglycemia. Three of them had presented with liver failure. Interestingly, one of them showed fluctuating liver functions, which worsened with infection and improved after aggressive treatment with antibiotics and supplements. Two of the four cases died in infancy, while the other two improved on conservative management with medium-chain triglyceride-based diet, vitamin supplements, co-enzyme Q and carnitine. The two surviving children are alive at 12 and 25 months of age with native liver with normal to mildly deranged liver function and no neurological dysfunction. Next-generation sequencing confirmed the diagnosis in all of our cases. One of the detected mutations, c.55delC (p.Gln19ArgfsTer3) is a novel pathogenic frameshift mutation, while another mutation c.388G>C (p.Ala130Pro), which was previously reported in Single Nucleotide Polymorphism Database in heterozygous form, is being predicted as likely pathogenic in our case series. We, therefore, propose mutation testing for MPV17 gene during evaluation of indeterminate infantile liver failure, especially those with hypoglycemia and raised plasma lactate.