A 8- year Bangladeshi girl with disseminated histoplasmosis, presented as chronic liver disease with portal hypertension: a rare case report.

BACKGROUND: Histoplasmosis is a rare infectious condition with mainly pulmonary involvement. Disseminated histoplasmosis may occur in immunocompromised condition. It can present in different ways but jaundice and ascites is very uncommon. CASE PRESENTATION: A 8- year old girl visited to department of pediatric gastroenterology & nutrition, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Child presented with fever, jaundice and abdominal distension for 2 ½ months. There was no history of contact with tuberculosis patient and travelling to kala-azar, malaria endemic zone and no history of previous jaundice, blood or blood product transfusion, history of sib death, family history of jaundice or neuropsychiatric disorder, significant weight loss. On general examination she was fretful, febrile, moderately icteric, mildly pale, vitally stable, severely wasted and moderately stunted, skin survey revealed infected scabies, BCG vaccine mark was absent, generalized lymphadenopathy, hepato-splenomegaly and ascites present. After evaluating the physical findings, several investigations was done including lymphnode biopsy, then the case was finally diagnosed as Disseminated histoplasmosis with portal hypertension. Child was treated with injectable Deoxycholate Amphotericin B for 28 days and improved on follow up. CONCLUSION: We suggest that children presenting with fever, jaundice, lymphadenopathy and hepatosplenomegaly and portal hypertension, disseminated histoplasmosis can be one differential.

Endoscopic Retrograde Cholangiopancreatography in Bangladeshi Children: Experiences and Challenges in a Developing Country.

Purpose: Although endoscopic retrograde cholangiopancreatography (ERCP) has been used for more than five decades, its applicability in Bangladeshi children has recently become more common. Therefore, this manuscript aims to describe our experience in performing ERCPs in Bangladeshi children with hepatopancreaticobiliary diseases, focusing on presenting diseases, as well as the diagnostic and therapeutic efficacy. Methods: Between 2018 and 2021, 20 children underwent 30 ERCP procedures at the Bangladesh Specialized Hospital, Dhaka. A single trained adult gastroenterologist performed all procedures using a therapeutic video duodenoscope. The indications for ERCP, diagnostic findings, therapeutic procedures, and complications were documented. Results: The median age of the study patients was 10 years (range, 1.7-15 years). Successful cannulation of the papilla was achieved in 28 procedures and failed in 2 cases. Repeated ERCP was required in seven patients. Nine patients had biliary indications and 11 had pancreatic indications. Choledocholithiasis was the most common indication for ERCP in patients with biliary disease, while chronic pancreatitis was common among patients with pancreatic indications. Pancreatic divisum was observed in only one patient. Pancreatic and biliary sphincterotomy was performed in 14 and 9 cases, respectively. A single pigtail or straight therapeutic stent was inserted in seven cases and removed in five cases. Stone extraction was performed in six procedures, and balloon dilatation was performed in five procedures. The post-procedural period for these patients was uneventful. Conclusion: We found that ERCP is a practical and successful therapeutic intervention for treating hepatopancreaticobiliary disorders in children when performed by experienced endoscopists.

Ratio of aspartate aminotransferase to alanine aminotransferase and alkaline phosphatase to total bilirubin in Wilsonian acute liver failure in children.

BACKGROUND: Acute liver failure (ALF) caused by Wilson disease (WD) is always fatal. Therefore, a quick diagnosis of WD is needed to start immediate management. This study aims to determine the ratio of aspartate aminotransferase to alanine aminotransferase (AST/ALT) and the ratio of alkaline phosphatase to total bilirubin (ALP/TB) in diagnosing Wilsonian acute liver failure (WALF) in children. METHODS: Sixty children with acute liver failure were included in this study, of whom 40 had WALF and 20 had a non-Wilsonian acute liver failure (non-WALF). The serum ALT, AST, alkaline phosphatase, and total bilirubin of each blood sample were measured. We evaluated the sensitivity and specificity of AST/ALT ratio and ALP/TB ratio in WALF diagnosis. RESULTS: Consanguinity and Kayser-Fleischer (K-F) rings were found in 32.5% and 72.5% of WALF cases, respectively. The mean hemoglobin, median ALT, median alkaline phosphatase, and mean ceruloplasmin of children with WALF were lower than those in the non-WALF group. In WALF cases, the median AST/ALT ratio was higher than in non-WALF cases. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of the ratio of AST to ALT were 70%, 95%, 96.5%, 61.3% and 78.3%, respectively. However, when the cutoff value is ≥ 1.85, the maximum sensitivity produced by the AST/ALT ratio is 77.5% and the specificity is 95%. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy of the ratio of ALP/TB < 4 were 32.5%, 100%, 100%, 42.5%, and 55%, respectively. The overall mortality rate was 50%, while the WALF mortality was 60%. CONCLUSION: A positive AST/ALT and ALP/TB ratio strongly suggest WALF, but a negative result does not exclude WALF. We cannot use these ratios as a diagnostic tool for children with WALF. In WALF cases, the mortality rate is remarkably high, and the high score of the new Wilson index predicts the mortality rate without liver transplantation.

A Comparative Study Between Cytomegalovirus Immunoglobulin M-Positive and CMV Immunoglobulin M-Negative Biliary Atresia in Infants Attending a Tertiary Care Hospital in Bangladesh.

Purpose: Perinatal cytomegalovirus (CMV) infection can lead to biliary atresia (BA) in different entities. This study aimed to compare the clinical, hematological, biochemical, and histological features of infants with BA based on their CMV immunoglobulin M (IgM) status at presentation. Methods: This cross-sectional descriptive study was carried out between January 2019 and June 2020 at the Department of Pediatric Gastroenterology and Nutrition at the Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka. Forty-three patients with BA were selected purposively and categorized into either the CMV IgM-positive or CMV IgM-negative BA group. Categorical variables were compared using Fisher's exact test and chi-square tests, while the Student's t-test and Mann-Whitney U-test were used to compare continuous variables. For all statistical tests, a p-value <0.05 was considered statistically significant. Results: Thirty-three (76.7%) of the cases were between 2 and 3 months of age on admission. The clinical, hematological, and biochemical parameters did not differ significantly between the CMV IgM-positive and CMV IgM-negative BA groups. Most (50.0%) of the CMV IgM-positive cases had fibrosis stage F2, while 43.5% of the CMV IgM-negative cases had fibrosis stage F3, with no significant difference between the groups (p=0.391). Conclusion: Our data shows no significant distinction between CMV IgM-positive and CMV IgM-negative BA, suggesting that CMV does not contribute to BA pathogenesis.

Juvenile Polyps in Bangladeshi Children and Their Association with Fecal Calprotectin as a Biomarker.

PURPOSE: Colonoscopy is considered the most reliable method for the diagnosis of juvenile polyps. However, colonoscopic screening is an invasive and expensive procedure. Fecal calprotectin (FCP), a marker of intestinal inflammation, has been shown to be elevated in patients with polyps. Therefore, this study aimed to evaluate FCP as a screening biomarker for the diagnosis of juvenile polyps. METHODS: This cross-sectional, observational study was conducted at the Pediatric Gastroenterology and Nutrition Department, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. For children with polyps, colonoscopic polypectomy and histopathology were performed. FCP levels were analyzed before and 4 weeks after polypectomy in all patients. Information was recorded in a datasheet and analyzed using the computer-based program SPSS. RESULTS: The age of the children was between 2.5 and 12 years. Approximately 93% of the polyps were found in the rectosigmoid region. Children with juvenile polyps had elevated levels of FCP before polypectomy that subsequently normalized after polypectomy. The mean FCP levels before and after polypectomy were 277±247 µg/g (range, 80-1,000 µg/g) and 48.57±38.23 µg/g (range, 29-140 µg/g) (p<0.001), respectively. The FCP levels were significantly higher in patients with multiple polyps than in those with single polyps. Moreover, mean FCP levels in patients with single and multiple polyps were 207.6±172.4 µg/ g and 515.4±320.5 µg/g (p<0.001), respectively. CONCLUSION: Colonic juvenile polyps were found to be associated with elevated levels of FCP that normalized after polypectomy. Therefore, FCP may be recommended as a noninvasive screening biomarker for diagnosis of colonic juvenile polyps.

Mutational analysis of exon 8 and exon 14 of ATP7B gene in Bangladeshi children with Wilson disease.

BACKGROUND : Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the Adenosine Triphosphate 7B (ATP7B) gene. The spectrum of ATP7B mutation varies in different populations. The objective of this study was to identify the mutation in exon 8 and exon 14 of ATP7B gene in Bangladeshi children clinically diagnosed as WD. We also aimed to explore the phenotypic presentation. METHODS: It was a cross sectional observational study. The study was conducted at the Department of Paediatric Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2017 to June 2018. A total of 37 patients diagnosed with WD were enrolled for the study. Venous blood (about 3 mL) was drawn aseptically from each patient into tube containing ethyline diamine tetraacetic acid (EDTA) and preserved at -30°C for long-term preservation. The peripheral blood leukocytes of the patients and genomic DNAs were extracted. Exons 14 and 8 of ATP7B and their associated splice-site junctions were amplified by the polymerase chain reaction (PCR). The size and quantity of PCR products were verified by electrophoresis in 1.5% (w/v) agarose gel. 74 (37 × 2) PCR products were sent for Sanger Sequencing. The sequences were analyzed by Chromas version 2.6.6 software and the nucleotide blast was done by National Center for Biotechnology Information (NCBI) nucleoblast. Finally, the sequences were analyzed using AB Applied Bio systems and were matched with the reference sequences using MEGA software. RESULTS: In this study, a single novel homozygous mutation pLeu.1071Val in the exon 14 was found in every (100%) studied child clinically diagnosed with WD. Heterozygous mutation p.Gly1061Glu in exon14 was also found in 6 patients (11%) with WD, which is one of the common mutations in this disease. In exon 8, p.Arg778Leu mutation was detected in one patient (2.7%), which is common in the Chinese and the South Asian populations and was heterozygous. Two novel heterozygous missense mutations p.K785R (2.7%) and p.S744F (2.7%) were also found in two other children in the exon 8. CONCLUSION: We found three novel mutations in Bangladeshi children with WD, one of which may be tagged as founder mutation for Bangladeshi population. This finding indicates the necessity to study the mutation profiles of the whole ATP7B gene in our population for risk prediction. A further large-scale study will help in the development of a Mutational Data Base of Bangladeshi population with WD.

Atypical manifestations of acute viral hepatitis A in children in Bangladesh: Are these really uncommon?

BACKGROUND/AIM: The aim of this study was to find out the clinical spectrum of acute viral hepatitis A (AVH-A) infection in children, the relationship between atypical manifestations and laboratory findings and the outcome of patients with typical and atypical hepatitis A virus (HAV) manifestations. METHODS: From January 2018 to September 2019, consecutive children (<18 years of age) with features suggestive of AVH with positive IgM anti-HAV both from inpatient and outpatient services were included in this study. Detailed history, physical findings, and investigations were recorded in the study questionnaire. Patients were followed up weekly until complete recovery. The Statistical Package for the Social Sciences (SPSS) version 22 was used for statistical analysis. RESULT: The mean age of 200 children who were finally included in the study was 8.3±3.5 years with male to female ratio of 134:66. Atypical features were present in 30 (15%) children; prolonged cholestasis (17, 8.5%), ascites (12, 6%), pleural effusion (4, 2%), thrombocytopenia (2, 1%), and hemolysis (1, 0.5%) were observed. Pruritus (p=0.005), higher serum total and direct bilirubin (p=0.00 and 0.001 respectively), and lower serum albumin (p=0.01) levels were statistically significant in children with atypical manifestations. Moreover, this group had prolonged mean duration of jaundice and hospital course (p=0.00 and 0.083 respectively). CONCLUSION: Atypical manifestations such as prolonged cholestasis and ascites are not uncommon in children with AVH-A in developing countries and seen in almost one-sixth of patients.

Omental Cyst - Rare Cause of Abdominal Pain in a 7-Year-Old Child: A Case Report.

INTRODUCTION: Abdominal pain is a common complaint in children. In most cases it may be functional. Among all organic causes, an abdominal cyst of omental or mesenteric origin is an uncommon etiology. CASE PRESENTATION: A 7-year-old girl presented with a short history of abdominal pain for 1 month associated with gradual abdominal distention. Physical examination revealed a large oval palpable firm, non-tender mass extending almost the whole abdomen. Imaging studies were suggestive of an intra-abdominal cyst, and the diagnosis was confirmed after exploratory laparotomy. The patient was managed surgically by enucleation of the cyst. CONCLUSION: Omental cysts are a rare benign condition, but should be considered as a diagnostic hypothesis in children with abdominal pain with or without a mass. It is difficult to diagnose an omental/mesenteric cyst clinically. A proper imaging study can guide the diagnosis. After confirming the diagnosis, the main treatment would be surgical excision.

INTRODUÇÃO: A dor abdominal é um sintoma comum durante a infância, mas na maioria dos casos é funcional. Entre as causas orgânicas potenciais, os quistos abdominais de origem epiplóica ou mesentérica são raros. CASO CLÍNICO: Uma menina de 7 anos de idade desenvolveu um quadro clínico caracterizado por dor e distensão abdominal gradual, com aproximadamente 1 mês de evolução. O exame objetivo revelou uma massa abdominal oval, de grandes dimensões, de consistência firme, mas indolor. Os estudos imagiológicos sugeriram a presença de um quisto intra-abdominal que se confirmou durante uma laparotomia exploradora. O tratamento foi cirúrgico e consistiu na enucleação do quisto. CONCLUSÕES: Os quistos epiplóicos são uma condição benigna rara, mas devem ser considerados no diagnóstico diferencial em crianças com dor abdominal, independentemente da presença de uma massa. O diagnóstico semiológico é difícil, mas um estudo imagiológico adequado pode ser esclarecedor. Após confirmação do diagnóstico a excisão cirúrgica é a modalidade terapêutica de eleição.

Non-endoscopic predictors of esophageal varices in children with chronic liver disease and their utility in resource-constrained countries.

BACKGROUND: Although endoscopy is the standard diagnostic screening test to identify esophageal varices in patients with chronic liver disease (CLD), selective endoscopy in patients who are at higher risk of having varices may be cost-effective in a resource-constrained country. The aim of this prospective study was to identify non-endoscopic parameters that may predict the presence of varices, especially high-risk esophageal varices in children with CLD. METHODS: From January 2016 through March 2018, consecutive children with CLD without a history of variceal bleeding were prospectively included. Esophagogastroduodenoscopy was done in all the children to detect and to grade esophageal varices. Both univariate and multivariate logistic regression analyses were done using SPSS version 22 to identify factors associated with esophageal varices. RESULTS: The mean age of 84 children was 9.7 ± 3.2 years (male 44). Esophageal varices were present in 71.4% of children and 55% of them had large varices. On univariate analysis, low platelet count (< 100,000/mm3) and splenomegaly were found to be associated with the presence of esophageal varices (p = 0.006 and 0.001, respectively) and large varices (p = 0.03 and 0.01, respectively). On multivariate analysis, both low platelet count and splenomegaly were independent predictors for the presence of esophageal varices (respectively, OR 11.21, 95% CI 1.2-96.9; and OR 11.39, 95% CI 3.19-40.59). CONCLUSIONS: Splenomegaly and low platelet count independently predict the presence of any grade of esophageal varices and can be used as screening tests to select children for endoscopy. This strategy may help in relieving medical, social, and economic costs in resource-constrained countries.

Bangladesh Environmental Enteric Dysfunction (BEED) study: protocol for a community-based intervention study to validate non-invasive biomarkers of environmental enteric dysfunction.

INTRODUCTION: Environmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting. METHODS AND ANALYSIS: The BEED study is a community-based intervention where participants are recruited from three cohorts: stunted children aged 12-18 months (length for age Z-score (LAZ) <-2), at risk of stunting children aged 12-18 months (LAZ <-1 to -2) and malnourished adults aged 18-45 years (body mass index <18.5 kg/m2). After screening, participants eligible for study provide faecal, urine and plasma specimens to quantify the levels of candidate EED biomarkers before and after receiving a nutritional intervention. Participants who fail to respond to nutritional therapy are considered as the candidates for upper gastrointestinal endoscopy with biopsy. Histopathological scoring for EED will be performed on biopsies obtained from several locations within the proximal small intestine. Candidate EED biomarkers will be correlated with nutritional status, the results of histochemical and immunohistochemical analyses of epithelial and lamina propria cell populations, plus assessments of microbial community structure. ETHICS AND DISSEMINATION: Ethics approval was obtained in all participating institutes. Results of this study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID: NCT02812615. Registered on 21 June 2016.

Caroli's disease.

Carolis disease is a rare communicating segmental or diffuse dilatation of the intrahepatic biliary tree. Cholangitis, liver cirrhosis and cholangiocarcinoma are its potential complications. A case of Carolis disease in a boy of 6 years with bilobal involvement presenting with intermittent abdominal pain, fever and hepatomegaly is reported here.

Ulcerative colitis in infancy.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder of colon. Frequency of UC is gradually increasing over few years worldwide. Prevalence is 35 to 100/100,000 people in USA, 1% of them are infants. UC develops in a genetically predisposed individual with altered intestinal immune response. An eight-month-old girl presented with loose bloody stool, growth failure, and moderate pallor. The girl was diagnosed as a case of UC by colonoscopy and biopsy. Treatment was thereafter started with immunosuppressive drugs. After initial induction therapy with parenteral steroid and infliximab, the patient is now on remission with azathioprine and mesalamine. UC is rare in Bangladesh, especially in children, and it is rarer during infancy. Several conditions like infective colitis, allergic colitis, Meckel's diverticulitis, Crohn's disease, etc. may mimic the features of UC. So, if a child presents with recurrent bloody diarrhea, UC should be considered as differential diagnosis.