Evaluation of Clinical Outcomes in Children with Intrahepatic Cholestasis Postpartial External Biliary Diversion: A Single-Center Experience.

Background: Severe pruritus caused by progressive familial intrahepatic cholestasis (PFIC) and Alagille syndrome (AGS) is refractory to medical treatment. Surgical interruption of the enterohepatic circulation is considered the mainstay of alleviating distressing symptoms and delaying cirrhosis. Aim and Objectives: This study aims to evaluate the short-term effect of partial external biliary diversion (PEBD) on pruritus, liver disease progression, patient's growth, and quality of life. Material and Methods: This prospective cohort study enrolled children with PFIC and AGS from July 2019 to July 2021, whose guardians consented to the PEBD procedure. A standard surgical approach was performed by a single surgeon. Outcomes were measured subjectively and objectively pre- and post-procedure using the pruritus 5-D itching score, Paediatric Quality of Life Inventory scale (PedsQL), growth parameters, bile acids level, and liver function tests. Patients' follow-up period ranged from 6 to 12 months. Results: Seven patients had PEBD procedure; five with PFIC and two with AGS. A significant improvement was detected in the 5-D itching score (p-value < 0.001), PedsQL (p-value < 0.001), and bile acids level (p-value 0.013). The preexisting growth failure was ameliorated. The downward trend in the bilirubin level was not significant. No influential difference in the other liver function tests occurred. No intra-operative complications encountered. Only one case had a post-operative stoma prolapse which was managed surgically. Conclusion: PEBD procedure could be considered as an effective and safe treatment options for intractable pruritus in patients with PFIC or AGS, providing preserved synthetic liver functions.

Patterns of respiratory tract infections in children under 5 years of age in a low-middle-income country.

BACKGROUND: Respiratory tract infections (RTIs) are among the most commonly encountered major public health problems, with a higher prevalence of lower RTIs among children and more generally the poor. The present study aimed to describe the pattern of respiratory tract infections in Egyptian children aged under 5 years and explore possible associations between socio-demographics and nutritional status and types of RTIs. METHODS: Over 6 months beginning in September 2018 (including one winter season), a cross-sectional, observational, epidemiological study was conducted on a sample of patients with upper and lower RTIs diagnosed clinically and/or radiologically in the outpatient clinics at Cairo University Children's Hospital in Egypt. An interview questionnaire was employed to collect socio-demographic and nutritional data. Heights/lengths and weights were measured and analyzed using the World Health Organization's (WHO) Anthro Plus [Computer Program]. Patients with pneumonia (n = 28) were compared to 97 healthy children of the same age and sex. RESULTS: The total number of children diagnosed with upper and lower respiratory infections was 611. Malnutrition was present in 12.4% of all children with upper and lower RTIs. Lower RTI and malnutrition were substantially more prevalent among children aged under 2 years (p = 0.048 and p < 0.001, respectively). The strongest predictor of lower RTI was a younger age (OR 0.797, CI 0.713-0.89, p < 0.001). CONCLUSION: At our center, approximately one-third of infections in under-fives were lower RTI. Malnutrition was one of the significant risk factors for lower RTI in children below 2 years. The nutritional status of infants and young children should be improved by encouraging exclusive breastfeeding during the first 6 months of life and strengthening the healthcare and nutritional counseling available for vulnerable children, particularly in rural regions.

Basic anthropometry, micronutrients status and growth velocity of patients with early-onset inflammatory bowel disease: A prospective cohort study.

BACKGROUND AND STUDY AIM: Failure of optimal growth and lack of appropriate weight gain are major nutritional problems in children with inflammatory bowel disease (IBD). Therefore, this study was designed to assess the nutritional and growth status of patients with very-early-onset IBD (VEO-IBD) before and after individual-based nutritional interventions. PATIENTS AND METHODS: This prospective cohort study assessed the nutritional status of 30 pediatric patients with VEO-IBD by performing comprehensive clinical examinations and evaluating anthropometric and biochemical parameters. The latter included the initial evaluation of serum albumin, prealbumin, minerals, and 25-hydroxyvitamin D. A 24-month nutritional strategy was designed for each patient. Patients who completed the study were reassessed after 6 months and their growth rate was calculated 2 years later. RESULTS: The initial assessment of malnutrition severity using the World Health Organization's z-score revealed that 36.7%, 43.3%, and 26.7% of the study group were underweight, stunted, and wasted, respectively. Among the study population, Crohn's disease has the highest prevalence. Almost all patients had micronutrient deficiencies (i.e., iron, calcium, zinc, magnesium, and vitamin D) and subnormal serum levels of nutritional markers (i.e., prealbumin and albumin). Six months after the intervention, a significant improvement in anthropometric and biochemical parameters was detected (p < 0.05); nevertheless, the calculated growth rate revealed a considerable decrease after 2 years. CONCLUSION: The early detection of nutritional impairment in patients with VEO-IBD remains a major challenge. Therefore, nutritional support and constant monitoring of these patients are necessary to ensure the improvement in their nutritional status and achieve an acceptable growth rate. Furthermore, we found that prealbumin could be a good discriminative tool for screening malnutrition in such patients.

Early myocardial functional abnormalities in primary dyslipidemia: clinical and echocardiographic observations in young children from a highly consanguineous population.

BACKGROUND: Dyslipidemia is a major health problem among children and adolescents worldwide due to its significant association with cardiovascular disease. Primary dyslipidemias are commonly familial syndromes that can be completely asymptomatic. PURPOSE: Apart from the risk of coronary artery disease (CAD), limited data are currently available on the direct effects of dyslipidemia on myocardial function in children. METHODS: We recruited 25 children with primary dyslipidemia (14 with isolated hypercholesterolemia, 4 with isolated hypertriglyceridemia, and 7 with combined dyslipidemia). Relevant clinical manifestations and laboratory and radiological investigations were evaluated. Pulsed-wave Doppler and tissue Doppler imaging echocardiography were performed for all recruited patients and the results were compared with those of 15 age- and sex-matched healthy children. RESULTS: The median age of the dyslipidemic children was 8 years (range, 1.5-16 years). A family history was documented in 13 cases (52%), while 18 (72%) had consanguineous parents. None of the dyslipidemic children had a personal history or clinical manifestations of CAD. In contrast, echocardiographic findings differed in several diastolic function parameters of both right and left ventricles in dyslipidemic children compared to controls. Based on normalized z scores, aortic valve narrowing was detected in 7 patients (28%), while narrowing of the aortic sinus (sinus of Valsalva) was detected in 15 patients (60%). CONCLUSION: Different types of primary dyslipidemia produce functional myocardial abnormalities early in childhood. Biochemical and echocardiographic screening of high-risk children is advised to minimize the incidence of serious cardiovascular complications.

Management strategy and novel ophthalmological findings in neonatal severe hypertriglyceridemia: a case report and literature review.

BACKGROUND: Neonatal severe hypertriglyceridemia is rarely reported in the literature and there is no consensus for hypertriglyceridemia management at this age group. METHODS: The index case is a 4-week-old male infant with severe hypertriglyceridemia accidentally discovered during a circumcision surgery. His clinical and genetic characteristics and his successful management strategy are described. Furthermore, a detailed ophthalmological examination of the proband was conducted at 3 and 6 months of age using Fourier-domain-optical coherence tomography. RESULTS: Triglycerides level at presentation was extremely high 33,727 mg/dL (380.8 mmol/L). Two sessions of exchange blood transfusion on two consecutive days successfully reduced triglycerides to 382 mg/dL (4.3 mmol/L) with no adverse effects. The infant was discharged 3 days later. At discharge, the mother was advised to continue breastfeeding together with a medium-chain triglycerides formula. Satisfactory growth parameters and lipid profile values were obtained for a follow-up duration of 5 months with no reported attacks of acute pancreatitis. Lipoprotein lipase deficiency was confirmed by the detection of the LPL homozygous pathogenic variant c.805G > A; p.(Glu269Lys). Early corneal and macular lesions were detected and persisted on follow-up despite relatively good lipemic control. CONCLUSION: This case highlights the importance of the early discovery of severe hypertriglyceridemia during the neonatal period, which is needed for prompt management and prevention of severe complications. Rationalized breastfeeding can be tolerated within the diet plan of the disease with satisfactory outcomes. To our knowledge, it is the first study reporting early corneal and macular affection by severe hypertriglyceridemia in a neonate. Prolonged follow-up is needed to determine the extent of ophthalmological lesions.

The value of different insulin resistance indices in assessment of non-alcoholic fatty liver disease in overweight/obese children.

OBJECTIVE: The aim of the present study was to determine the association between insulin resistance (IR) and both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in a group of Egyptian overweight/obese children and adolescents and to evaluate different IR indices in detection of NAFLD. PATIENTS AND METHODS: The study included 76 overweight/obese children aged 2-15 years; 52.6% were males. Laboratory analysis included fasting blood glucose, serum insulin, lipid profile, liver biochemical profile, and liver ultrasound. IR was calculated using the following indices; the homeostasis model assessment method (HOMA-IR), the quantitative insulin-sensitivity check index (QUICKI) and hepatic insulin sensitivity. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of MetS. Liver biopsy was done when medically indicated and accepted by parents. RESULTS: IR was detected in 43.4% and 34.2% by using QUICKI and HOMA, respectively. MetS was detected in 36.8% and NAFLD was detected in 45.5% among those performing liver biopsy. Cases with NAFLD had more frequent IR than children with normal histology. QUICKI showed significant difference between normal subjects and both steatosis and non-alcoholic steatohepatitis; while HOMA-IR was sensitive in cases with NASH only. MetS was present in 100% of patients with NASH and in 75% of those with steatosis and they were all obese. Patients with NASH had significantly higher ALT than those with normal histology. CONCLUSION: IR was significantly associated with NAFLD. QUICKI is considered more sensitive than HOMA-IR in differentiating simple steatosis from normal liver histology.

The association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children.

BACKGROUND/AIM: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). PATIENTS AND METHODS: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. RESULTS: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). CONCLUSION: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.

Genetic polymorphisms in non-alcoholic fatty liver disease in obese Egyptian children.

BACKGROUND/AIM: Polymorphisms in the promoter of microsomal triglyceride transfer protein (MTP) lead to decreased MTP transcription, less export of triglyceride from hepatocytes, and greater intracellular triglyceride accumulation. Therefore, functional polymorphisms in MTP may be involved in determining susceptibility to nonalcoholic steatohepatitis (NASH). The aim of this study is to examine the effect of some genetic influences among a group of obese Egyptian children. PATIENTS AND METHODS: A cross-sectional study was conducted on 76 overweight and obese children presenting to the Pediatric Endocrinology Unit, Cairo University Children's Hospital, Egypt, as well as on 20 healthy controls. Anthropometric measurements were taken for all the patients and they underwent clinical examination, ultrasonographic examination of the liver, and liver biopsy when appropriate. Liver functions, blood glucose, serum insulin, C-peptide, and lipid profile were assessed and HOMA-IR calculated. Blood samples from biopsy-proven NASH patients and controls were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism for the -493 G/T polymorphism in the promoter of MTP and the 1183 T/C polymorphism in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD). RESULTS: Eight had biopsy-proven simple steatosis and 7 had NASH. NASH patients had a much higher incidence of the MTP G/G genotype (P = 0.002, CI: 2.9-392) compared with the controls. NASH patients also had a 100% prevalence of the MnSOD T/T genotype. CONCLUSION: Certain genotypes in MTP and MnSOD are significantly more prevalent among obese children with NASH and may be responsible for such a phenotype.

Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian children: single center study.

BACKGROUND/AIM: Pediatric non-alcoholic fatty liver disease (NAFLD) is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. MATERIALS AND METHODS: Seventy-six children (2-15 years) were included after an informed consent. All were subjected to full anthropometric assessment (including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio), biochemical assessment of liver function tests, lipid profile and insulin resistance and sonographic assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33 patients. RESULTS: Sixteen patients (21%) had elevated ALT and 6 (7.9%) had elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high LDL-c and triglycerides) and higher insulin resistance were found in obese patients (P<0.01). The main sonographic findings were hepatomegaly in 20 patients (26.3%) and echogenic liver in 41 patients (53.9%). Liver biopsy showed simple steatosis in eight cases (24.2%) and non-alcoholic steatohepatitis (NASH) in seven cases (21.2%). Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor (independent variable) for NAFLD in both uni- and multivariate logistic regression analyses. CONCLUSION: Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children.

Study of predictive value of pediatric risk of mortality (PRISM) score in children with end stage liver disease and fulminant hepatic failure.

OBJECTIVE: To evaluate the use of the PRISM score as a predictor of outcome in patients with end stage liver disease (ESLD) and fulminant hepatic failure (FHF). METHODS: The present study included 30 patients with ESLD and FHF, with ages ranging from 2 to 108 months, who were admitted to the Emergency room (ER) and the Pediatric Hepatology Unit at Cairo University Children's Hospital (tertiary referral hospital) over a six-month-period from May through October 2008. Survivors were followed up for 6 months. Two other scores were also calculated, the PELD score and the Child-Pugh score. The outcome was defined as survivors and deceased. RESULTS: Deceased patients as compared with survivors were significantly younger (median age 7 vs. 24 months, p=0.003). A ROC curve was constructed for the PRISM score, the predicted death rate (PDR) and the PELD score in the 30 patients. PRISM score was significantly associated with mortality (p=0.04). The best cut off value was 9.5 (70.6% sensitive and 61% specific). PDR was also significantly associated with mortality (p=0.011). The best cut off value for PDR was 5.95 (70.6% sensitive, 85% specific). On the other hand, the PELD score was not associated with mortality (p=0.202). CONCLUSIONS: PRISM score can be applied with an adequate degree of accuracy for severity assessment and mortality prediction to pediatric patients with ESLD or FHF.

Alagille syndrome: clinical and ocular pathognomonic features.

PURPOSE: This study was carried out to determine the frequency of clinical diagnostic criteria in patients with Alagille syndrome (AGS) in comparison to a group of children with cholestasis and histologically proven neonatal hepatitis (NH). The type and frequency of ocular manifestations are highlighted. METHODS: According to histologic findings on liver biopsy, the 32 patients included in the study were classified into 2 groups: group 1 had paucity of interlobular bile ducts (PILBD) (n=13) and at least 3 of 5 characteristics of AGS and group 2 had NH on liver biopsy (n=19). RESULTS: The mean age of patients with AGS was higher than in group 2 (3.9 vs 1.6 years) (p<0.05). Pruritus was a significant symptom in the AGS group (p<0.05). Characteristic facies was detected in 61.5% of the AGS group. None of our patients with AGS had vertebral anomalies. Although cardiac murmurs were heard in 5 patients with AGS, cardiac anomalies were detected in only 3 by echocardiography: pulmonary stenosis in 2 patients and patent foramen ovale in 1. Posterior embryotoxon (PE) was detected in 69.2% of patients with AGS as compared to 10.5% of the NH group. Optic nerve drusen was detected in 91% of patients with AGS as compared to 5.3% of patients with NH. CONCLUSIONS: Optic nerve drusen was the most common finding in AGS, followed by PE and facial features. Ocular ultrasound needs to be performed in all cholestatic infants with PILBD.

A comparative study of endoscopic ultrasonography versus endoscopic retrograde cholangiopancreatography in children with chronic liver disease.

BACKGROUND: Endoscopic ultrasonography (EUS) is a less invasive modality and may be equal or superior to endoscopic retrograde cholangiopancreatography (ERCP) in visualizing the biliary tree. Its role and feasibility in children need to be accurately defined. AIM: This study aimed at evaluation of EUS in assessment of children with chronic liver disease (CLD) in comparison with ERCP. MATERIALS AND METHODS: The present study was carried out between September 2004 and February 2006 on 40 children suffering from CLD. Patients were selected from the Pediatric Hepatology Unit, Cairo University Children's Hospital, Egypt. They were included if they had: sonographic (n = 8) or histopathological evidence of biliary pathology (n = 2); autoimmune hepatitis with high gamma glutammyl transpeptidase (GGT) levels and/or not responding to immunosuppressive therapy (n = 15); cryptogenic CLD (n = 13); neonatal cholestasis with relapsing or persistent course (n = 2). They all underwent EUS and ERCP. RESULTS: Three of six cases with intrahepatic biliary radicle dilatation had Caroli's disease by EUS and ERCP; and the other 3 had sclerosing cholangitis. EUS was equal to ERCP in diagnosis of biliary pathology. However, one false positive case was described to have dilatation and tortuosity of the pancreatic duct by EUS as compared to ERCP. EUS could detect early pancreatitis in 5 cases. One case with cryptogenic liver disease proved to have sclerosing cholangitis by both EUS and ERCP. CONCLUSION: EUS is an important diagnostic tool for biliary pathology and pancreatitis in children with pancreatico-biliary pathology. ERCP should be reserved for therapeutic purposes.