Comparison of Serum Zinc in Children of Wilson Disease and Non-Wilsonian Volunteers in Bangladesh.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism with diverse clinical manifestations. Zinc (Zn) has been used for treatment of WD. Recent studies showed low serum zinc level in patients suffering from WD than the normal. This cross-sectional analytical study has been designed to compare the serum zinc level between paediatric patients suffering from WD but yet not started treatment and children who have normal ALT level. This study was carried out at the Department of Pediatric Gastroenterology and Nutrition, BSMMU, Dhaka, Bangladesh from July 2018 to June 2019. Total 51 children were included in this study. Among them 27 were diagnosed case of WD aged between three to eighteen years and 24 children of same ages who were suffering from other than liver disease having normal ALT were included as volunteers. The patients of WD were divided into four groups according to their presentation as acute hepatitis, chronic liver disease (CLD), acute liver failure & neuropsychiatric manifestation. Informed written consent was obtained from all patients and volunteers for participation in this study. Along with other physical findings and laboratory investigations 3 ml of venous blood were collected for estimation of serum zinc level. After estimation of serum zinc level results were analyzed statistically. The difference in serum zinc levels were compared between the groups. Serum zinc level was significantly lower in Wilson disease patients (43.8±19.7µg/dl; range: 13-83) compared to volunteers group (67.8±11.8µg/dl; range: 47-97) p<0.001. Among the diseased group, serum zinc level were significantly lower in 18 CLD (38.4±17.4µg/dl) and in 4 acute liver failure (33.1±3.7µg/dl) compared to 4 acute hepatitis (71.8±4.3µg/dl) (p=0.001) and (p<0.001) respectively. Mean serum zinc level was low in 4 Wilsonian acute liver failure (33.1±3.7µg/dl), which was significant compared to those (23) who presented as Wilson disease non acute liver failure (45.7±20.8µg/dl) (p=0.013). Serum zinc level was significantly lower in Wilson disease children compared to the volunteers. Zinc level was also found significantly low in Wilson disease presented as CLD and acute liver failure in comparison to Wilson disease presented as acute hepatitis.

Evaluation of Fecal Pancreatic Elastase-1 as a Measure of Pancreatic Exocrine Function in Children with Pancreatitis.

Pancreatic exocrine insufficiency occurs as a clinical consequence of chronic pancreatitis leading to fat maldigestion, malabsorption and malnutrition. Fecal elastase-1 is a laboratory-based test used for the diagnosis or exclusion of pancreatic exocrine insufficiency. The aim of the study was to observe the value of fecal elastase-1 in children with pancreatitis as an indicator of pancreatic exocrine insufficiency. This was a cross-sectional descriptive study conducted from January 2017 through June 2018. Thirty children with pain abdomen as control and 36 patients with pancreatitis as cases were included. An ELISA technique which recognizes human pancreatic elastase-1 from spot stool sample was employed for the test. Fecal elastase-1 activity in spot stool samples in acute pancreatitis (AP) ranged from 198.2-500µg/g with a mean of 342.1±136.4µg/g, acute recurrent pancreatitis (ARP) ranged from 15-500µg/g with a mean of 332.8±194.5µg/g and chronic pancreatitis (CP) ranged from 15-492.8µg/g with a mean of 222.2±197.1µg/g was obtained. In controls, fecal elastase-1 ranged from 28.4-500µg/g with a mean of 398.8±114.9µg/g. Disease severity was classified as mild to moderate pancreatic insufficiency (fecal elastase-1 100 to 200µg/g stool) was found in AP (14.3%) and CP (6.7%) cases. The severe pancreatic insufficiency (fecal elastase-1<100µg/g stool) was observed in ARP (28.6%) and CP (46.7%) cases. Malnutrition was observed in severe pancreatic insufficiency cases. This study result showed that fecal elastase-1 can be used as a measure of pancreatic exocrine function in children with pancreatitis.

Diagnostic Value of Serum Gamma Glutamyl Transpeptidase (GGT) for Early Diagnosis of Biliary Atresia.

Early differentiation of biliary atresia (BA) from idiopathic neonatal hepatitis (INH) is of important as outcome of Kasai portoenterostomy is directly related to the age of surgery. We need to have a simple and cheap biochemical test in resource poor countries like Bangladesh, to pick up BA early. Serum gamma glutamyl transpeptidase (GGT) has been shown to be a useful marker to differentiate BA from INH. Objective of the study was to find out the diagnostic value of gamma glutamyl transpeptidase (GGT) in differentiating Biliary atresia (BA) from idiopathic neonatal hepatitis (INH). This observational cross section study was carried out at the Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Study period was from January 2014 to June 2015. Consecutive infants with neonatal cholestasis (defined as conjugated bilirubin >1.0mg/dL when total bilirubin was ≤5.0 or >20.0% to total bilirubin) were included in this study. Clinical details and the results of laboratory tests were recorded in a proforma. BA was diagnosed on the basis of liver biopsy. Different biochemical parameters especially the results of serum GGT level (normal up to 60U/L), were compared between two groups (BA and INH). Receiver Operator Characteristic (ROC) curve for GGT was constructed to find out the best cut off value to discriminate BA from INH by using SPSS (version 20.0). After confirming cholestasis, a total of 165 cases were enrolled for study. Among them 86 cases were diagnosed as INH or BA. Among these 86 cases, 38(44.2%) cases were BA and 48(55.8%) cases were INH. On comparing 38(44.2%) cases of BA with 48(55.8%) cases of INH it was found that low birth weight (13.0% vs. 31.0%, p<0.05), persistently acholic stools (76.0% vs. 44.0%, p=0.002) and mean GGT values (921 vs. 264, p<0.001) were significantly different between them. At a cut off value of 524U/L (8.7 times upper limit of normal) the area under curve (AUC) for GGT was 0.81 with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 81.7%, 72.9%, 70.5%, 83.3% and 76.1% respectively for the diagnosis of Biliary atresia. Serum GGT value of >524 U/L or 8.7 times upper limit of normal value was fairly good in differentiating BA from INH and can be used as a screening investigation in developing countries.

Efficacy of Different Diagnostic Test for Identifying Wilson's Disease.

Wilson disease is an autosomal recessive disorder in which copper pathologically accumulates primarily within the liver, brain and other tissues. It can presents clinically as liver disease, as a progressive neurological disorder or as psychiatric illness. The wide array of clinical manifestations of WD can lead to misdiagnosis with subsequent greater risk of irreversible damage to liver and brain. Many tests can be used to investigate patients of Wilson disease, including serum free copper, 24 hours urine copper estimation, hepatic copper estimation and genetic mutation testing. But there is no single ideal diagnostic test that can exclude or confirm the disease with certainty. The aim of the study was to find out the efficacy of different diagnostic test for the diagnosis of Wilson disease. This cross-sectional analytical study was conducted at department of Paediatric Gastroenterology and Nutrition of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh from January 2016 through January 2018. A total of 56 cases of Wilson disease and 39 patients with a liver disease other than WD were studied. Wilson disease was diagnosed by Leipzig score. Along with other physical findings and laboratory investigations slit lamp eye examination for KF ring, serum ceruloplasmin and 24 hour urinary copper excretion were done. The mean age of WD patients was 9.69±2.37 years, male female ratio was 1:1. Serum ceruloplasmin level was significantly lower in WD patient (p<0.001). Median of 24 hour urinary copper in WD was 702.75µg/ 24 hr (range119-11210µg/24 hour) and in non WD group it was 77.41µg/24 hour (range 20.0-478µg/24 hour) and the difference between them is statistically significant (p=0.001). The sensitivity of KF ring was 82.1% and specificity was 100%. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of serum ceruloplasmin were 98.2%, 92.3%, 94.8%, 97.2% and 95.7% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 24 hour urinary copper were 100%, 63%, 80% and 85.1% respectively. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of KF ring, serum ceruloplasmin and basal 24 hour urinary copper excretion when combined together came out to be 70.4%, 100%, 100%, 59.3% and 79.3% respectively. This study result showed that serum ceruloplasmin and 24 hour urinary copper can be used as a screening test for the diagnosis of Wilson disease.

Chronic Hepatitis B in Children - A Review.

Hepatitis B Virus (HBV) infection is prevalent worldwide. The prevalence is lowest (0.2-0.5%) in countries having high standard of living. About 10 million people are chronically infected with HBV in Bangladesh and it is possible that most infections occur during childhood. Overall prevalence is about 3% in Bangladesh. Perinatal transmission is more common in hyper-endemic areas of South East Asia. Chronic hepatitis B infection evolves through five phases. Most of the children belong to immune tolerant phase. About 57% patients of chronic hepatitis B are asymptomatic. Treatment of chronic hepatitis B is difficult. Decision regarding when, whom and how to treat in children is complex. Moreover, there are only limited drugs that can be used in treating chronic hepatitis B in children. Goal of therapy are to reduce viral replication, to minimize liver injury, to reduce consequence of liver injury like cirrhosis, hepatocellular carcinoma and to reduce infectivity of HBV. Treatment should be considered in chronic hepatitis B if patient have persistently elevated ALT of more than twice normal and evidence of viral replication. There are some special circumstances where treatment of chronic hepatitis B can be given in absence of standard criteria. These conditions are cirrhosis, chemotherapy, immunosuppression, presence of co-infection (HBV-HIV), family history of HCC and pregnant women with high viral load. Sero-conversion occurs in about 17-32% cases if treated with oral nucleot(s)ide analogue and in about 58% cases if treated with interferon. These expensive drugs with limited treatment success are not suitable for the people of Bangladesh. Therefore, risk factors identification and prevention of HBV infection is the logical and rational approach for a country like Bangladesh. Vaccination against HBV play central role in preventing infection. HBV vaccine has been incorporated in EPI schedule since 2004 in Bangladesh. Immunoprophylaxis of babies of HBsAg positive mother and post exposure prophylaxis are effective ways of prevention.

Penicillamine challenge test in the diagnosis of Wilson's disease.

Wilson's disease (WD) is one of the most common metabolic liver diseases encountered in children. Early diagnosis of the disease is essential because specific treatment can be offered, that will prevent further hepatocellular injury and neurologic complications. There is no single diagnostic test that can exclude or confirm the disease with certainty. Penicillamine challenge has proved itself to be a useful diagnostic test in the detection of WD. The main purpose of this study was to observe the reliability of penicillamine challenge test, in the diagnosis of WD. The cross sectional study was done with a case control design in the department of paediatric gastroenterology & Nutrition, BSMMU, Dhaka. The study was carried out on 60 patients of CLD. Along with other physical findings and laboratory investigations, 24 hours urinary copper excretions were estimated before and after penicillamine challenge. Study results were analyzed statistically. Thirty CLD patients who fulfilled the inclusion and exclusion criteria of WD were considered as cases (Group I) and remaining 30 CLD patients were considered as non-Wilsonian CLD and was labeled as control (Group II). Among the control group, 12 CLD patients were found to be HBsAg positive, 1 had hepatitis-C virus infection, 1 had autoimmune hepatitis and the remaining 16 CLD patients were Cryptogenic. The (mean±SD) age of WD patients was 9.90±28 years; male female ratio was 1.5:1. Most common presentation was ascites (70%). K-F ring was found in 86.7% cases. Serum ceruloplasmin level was found significantly lower in WD patients (mean±SD, 0.1197±23g/L, p<0.001). Baseline urinary copper excretion of WD patients differed significantly from controls (Median 219.0µg/24hour, range 35-2018µg/24hour, versus median 44µg/24hour, range 20-238µg/24hour, p<0.001). Baseline urinary copper excretion above 100µg/24hour was observed in 80% WD patients whereas it was 10% in controls. post penicillamine urinary copper excretion was significantly greater in WD patients than controls (Median 2635µg/24hour, range 648-6222µg/24hour, versus median 423µg/24hour, range 91-1250µg/24hour, p<0.001). Post penicillamine urinary copper above 1600µg/24hour observed in 70% of WD patients whereas not a single patient reached the value in control group. Twenty four hours urinary copper estimation after penicillamine challenge was found to be a valuable test in the diagnosis of WD.

Wilson's disease in children with blindness: an atypical presentation.

Wilson's disease (WD) is an autosomal recessive disease affecting copper metabolism causing copper induced organ damage. Common organs involved are liver and central nervous system. But RBC, eye, kidneys and bone may also be affected. In WD main defect remains in copper transporter protein p type ATPase resulting from gene mutation in chromosome 13. Neurological manifestations in WD develop due to deposition of copper in different brain areas like basal ganglia, cerebral cortex, corticospinal and corticobulbar pathway. Different types of neurological manifestations develop in WD but visual impairment is very rare. A 14 years old boy of WD presented to us with blindness, tremor and slurred speech along with end stage liver disease. Blindness was thought to be due to optic neuropathy which reversed after drug treatment.

Wilson's disease with hepatic presentation in childhood.

Diagnosis of Wilson's disease with hepatic presentation in childhood using clinical and common laboratory parameters is still challenging and is often missed or delayed. The aim of the study was to document the clinical and laboratory parameters of hepatic presentation of Wilson's disease in children. The study was conducted at a tertiary-care hospital in a developing country. Clinical and common laboratory parameters were recorded in 32 Wilson's disease children with hepatic presentation. The diagnosis was based on positive family history, Kayser-Fleischer ring, low serum ceruloplasmin level, elevated basal urinary copper excretion and favorable response to therapy with D-penicillamine. Mean age+/-SD at presentation was 9+/-2.97 years and 21 (65.6%) were boys. Chronic liver disease (21; 65.6%) followed by fulminant hepatic failure 1(6; 18.8%) were the commonest presentation. In the whole group, Kayser-Fleischer ring was found in 21 (65.6%), low serum ceruloplasmin in 16 (50%) and elevated basal urinary copper excretion in all 32 (100%) children. Diagnosis of Wilson's disease was made at presentation on the basis of i) Kayser-Fleischer ring, low serum ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 11 (34.4%), ii) Kayser-Fleischer ring, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 10 (31.2%), iii) elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 6 (18.8%) and iv) low ceruloplasmin, elevated basal urinary copper excretion and favorable response to D-penicillamine therapy in 5 (15.6%) children. Wilson's disease can not be excluded in children presenting with hepatic involvement using the commonly practiced clinical and laboratory parameters. A combination of various clinical and laboratory parameters were used for the diagnosis of Wilson's disease in the studied children with hepatic presentation.