Clinical experience with hepatorenal tyrosinemia from a single Egyptian center.

Although very recently, in Egypt, sick newborn screening has included screening for hepatorenal tyrosinemia, yet, it is not yet included in nationwide neonatal screening and hence diagnosis may be delayed. The aim of this study was to analyze data of all cases presenting with hepatorenal tyrosinemia to the Pediatric Hepatology Unit, Cairo University, Egypt from 2006 to 2019. Data were retrieved from patients' files including age of onset of symptoms, clinical signs, blood counts, liver functions, serum phosphorous, alpha-fetoprotein, succinylacetone and abdominal ultrasound. During this period, 76 patients were diagnosed with hepatorenal tyrosinemia if succinylacetone in dry blood spot was elevated above 1 µmol/L. These 76 cases came from 70 families; consanguinity was reported in 61 families. In our cohort we reported 30 affected siblings with a similar clinical presentation, who died undiagnosed. Presentation was acute in 26%, subacute in 30% and chronic in 43%. Abdominal distention was the commonest presenting symptom (52.6%). Coagulopathy was the commonest derangement in liver functions; hyperbilirubinemia and raised transaminases were less common. Ultrasound findings included hepatic focal lesions in 47% and enlarged echogenic kidneys in 39% and 45.3% respectively. Only 20 children were treated with Nitisinone because of unavailability and high costs; seven out of them underwent liver transplantation. In conclusion, although hepatorenal tyrosinemia is a rare inborn error of metabolism, in a large population country with high rate of consanguinity; this disease is not uncommonly diagnosed. The current treatment is not readily available because of the costs in a resource-limited country. Neonatal screening and subsidization of the costly medication need to be considered.

Association of Helicobacter pylori and parasitic infections in childhood: impact on clinical manifestations and implications.

The association of Helicobacter pylori (H. pylori) infection and parasitic infections including Giardia lamblia (G. lamblia), especially in childhood, is widely recognized to be high in developing communities. We aimed to study the impact of concomitant intestinal parasitic and H. pylori infections on the different clinical presentation of infected children and whether this coinfection could in turn cause any alteration in the clinical manifestations of each other. This cross-sectional study included 150 children of both sexes with their age ranging from 1 to 15 years, having gastrointestinal complaints, throughout 8 months duration. All cases were subjected to full history taking, clinical examination and stool analysis by direct wet smear and formalin-ethyl acetate concentration technique, permanent staining with cold acid fast stain in addition to H. pylori coproantigen detection in stool. Parasitic infection was recorded in 58.6% of patients, with G. lamblia the most detected parasite (35.2%). Cases infected with H. pylori were 63 cases (42%) of which 61.9% of cases showed associated parasitic infection. Diarrhea was the most frequent complaint (63.2%) in cases infected with intestinal parasites, while it was less frequently recorded in co-infected cases (35.8%) and in cases with H. pylori infection only (29.1%) (P value 0.0008). On the other hand, vomiting was less recorded in coinfected cases than cases with H. pylori infection. Coinfection with intestinal parasites (including G. lamblia) and H. pylori could modulate the clinical manifestation of each other especially diarrhea in parasitic infections and vomiting in H. pylori infection.

Right ventricular functions in subphenotypes of sickle cell disease.

OBJECTIVES: Sickle cardiomyopathy is the most important cause of death in patients with sickle cell disease (SCD). Based on recent evidence, SCD can be divided into two subphenotypes, namely, the viscosity vasoocclusion (VVO) subphenotype and the hemolysis endothelial dysfunction (HED) subphenotype. The aim of our series is to study right ventricular (RV) functions in both subphenotypes. METHODS: Echocardiography including conventional and tissue Doppler imaging as well as speckle tracking echocardiography was performed in 50 patients (23 from the VVO subgroup and 27 from the HED subgroup) based on a serum lactate dehydrogenase (LDH) level below or above 270 U/L, respectively, and in 50 controls. Reticulocyte count and hemoglobin levels were assessed in different groups of patients. RESULTS: The HED subgroup showed RV dysfunction. Patients in this subgroup also showed systolic and diastolic functions similar to those seen in the VVO subgroup and controls. In addition, a tight correlation exists between LDH and both RV global longitudinal strain (-0.68) and RV E/E' ratio (0.9), defined as the ratio of early diastolic tricuspid inflow velocity to tricuspid annular early diastolic velocity. CONCLUSIONS: Results reveal a marked discrepancy in RV functions between HED and VVO subphenotypes of SCD, with patients in the former subgroup being more prone to RV dysfunction. This warrants early screening of such patients in daily practice.

Discrepancy in patterns of myocardial involvement in beta-thalassaemia vs. sickle cell anaemia.

Introduction: Different mechanisms contribute to myocardial dysfunction in sickle cell disease [SCD] and beta thalassaemia major [TM]. TM mainly involves the highly vascular subepicardium by iron load and SCD mainly operates by inducing ischaemia in the relatively ischaemic subendocardium. The aim of this article was to determine if pattern of left ventricular [LV] dysfunction differ among the two groups of patients.Methods: Forty TM and 40 SCD patients and 40 age- and surface area-matched controls were subjected to conventional echocardiography, 2D Speckle tracking myocardial layer strain discriminating echocardiography (MLSD-STE) which is able to discriminate if myocardial dysfunction is predominantly subepicardial or subendocardial and 3D echocardiography for ejection fraction assessment as well as haemoglobin, ferritin, and lactate dehydrogenase levels.Results: TM patients had a deeper subepicardial dysfunction while SCD had prevalent subendocardial dysfunction, epicardial GLS (TM: -10.9 ± 2 vs. SCD: 19.9 ± 1.7; p value < 0.01); endocardial GLS (TM: -19.9 ± 1.7 vs. SCD: -10.6 ± 1.6, p value < 0.01).Conclusion: This study points towards divergent microcirculatory mechanisms in the pathogenesis of myocardial dysfunction in haemoglobinopathies. It shows predominant subendocardial dysfunction with underlying ischaemia of SCD and prevalent subepicardial iron-induced injury in cases of TM.

Drug-Drug Interactions in Children and Adolescents Receiving Ledipasvir/Sofosbuvir for the Treatment of Hepatitis C Virus Infection.

BACKGROUND AND OBJECTIVE: Drug-drug interactions need to be considered to optimize the pharmacotherapeutic outcome of direct-acting antivirals. The aim of this study was to report on possible drug-drug interactions between ledipasvir/sofosbuvir and other medications received by children and adolescents with hepatitis C virus, in addition to suggested management for these drug-drug interactions. METHODS: Hepatitis C virus-infected children and adolescents, 12-17 years of age and/or weighing ≥ 35 kg, who presented to the Pediatric Hepatology Unit at Cairo University Pediatric Hospitals for ledipasvir/sofosbuvir treatment were included. Medication history was taken including long-term medications for chronic conditions and on-demand medications for inter-current illnesses. Medications were reviewed by the Kasr Alainy Drug Information Center to identify possible drug-drug interactions with prescribed ledipasvir/sofosbuvir and their management. HEP Drug Interactions provided by the University of Liverpool, Lexicomp®, and Medscape were the utilized references. Each drug-drug interaction was assigned a risk rating of A, B, C, D, or X. RESULTS: Sixty hepatitis C virus-infected children and adolescents assigned to receive ledipasvir/sofosbuvir were enrolled. Thirty percent of patients had associated chronic co-morbid conditions. The overall number of medications received was 48; 39 were prescribed as long-term medications with a median of 3 (interquartile range 4.24) medications per patient. Proton pump inhibitors, antacids, histamine H2 receptor antagonists, sodium bicarbonate, and colchicine were reported to be associated with a drug-drug interaction risk D necessitating therapy modification, which occurred prior to administration. CONCLUSIONS: Early identification and prompt response to drug-drug interactions with the aid of pharmacists optimize the pharmacotherapeutic outcome and eliminate possible morbidities when using direct-acting antivirals in children and adolescents with hepatitis C virus.

Urinary abnormalities in children and adolescents with Wilson disease before and during treatment with d-penicillamine.

BACKGROUND AND AIM: Renal abnormalities can occur at any time point during the course of Wilson disease (WD). We aimed to fill a literature gap in this respect by studying urinary abnormalities in children and adolescents with WD. METHODS: This study included 60 children with WD presenting to the Pediatric Hepatology Unit, Cairo University. The following data were retrieved from the patients' files including age, sex, liver function tests, serum ceruloplasmin, 24-h urinary copper, serum creatinine, blood urea nitrogen, urinalysis, urinary albumin/creatinine ratio, urinary calcium/creatinine ratio, urinary ß2-microglobulin, liver and renal biopsy results when available. RESULTS: All studied cases had no symptoms related to renal involvement. Microscopic hematuria was detected in 11% and 12% at baseline and within 5 years of therapy, respectively. Moderate microalbuminuria was detected in 34%, 50%, and 33% at baseline, within 5 years and > 5 years after therapy, respectively. Hypercalciuria was detected in 23% at baseline, 34% in those patients treated for up to 5 years and 37.5% > 5 years of therapy. Age and international normalized ratio were significantly higher in patients with high calcium/creatinine ratio compared with those with normal values at initial evaluation. Frequency of elevated urinary ß2-microglobulin was 36%, 36%, and 37% in patients at baseline, up to 5 years and > 5 years of therapy, respectively. CONCLUSION: Asymptomatic urinary abnormalities are present in patients with WD at any time point of the disease and during treatment with d-penicillamine. They have to be searched for, as early intervention may prevent progression to renal insufficiency.

Histopathological changes in the oesophageal mucosa in Egyptian children with corrosive strictures: A single-centre vast experience.

BACKGROUND: The caustic ingestion continues to be a major problem worldwide especially in developing countries. The long-term complications include stricture and increased life time risk of oesophageal carcinoma. Patients suffered from corrosive induced oesophageal strictures have more than a 1000-fold risk of developing carcinoma of the oesophagus. AIM: To determine the possibility of oesophageal mucosal dysplasia after prolonged dilatation in post corrosive stricture. METHODS: This observational study was conducted at the Paediatric Endoscopy Unit in Cairo University Children's Hospital. It included children of both sexes older than 2 years of age who had an established diagnosis of post-corrosive oesophageal stricture and repeated endoscopic dilatation sessions for more than 6 mo. All patients were biopsied at the stricture site after 6 mo of endoscopic dilatation. A histopathological examination of an oesophageal mucosal biopsy was performed for the detection of chronic oesophagitis, inflammatory cellular infiltration and dysplasia. RESULTS: The mean age of the enrolled children was 5.9 ± 2.6 years; 90% of the patients had ingested an alkaline corrosive substance (potash). The total number of endoscopic dilatation sessions were ranging from 16 to 100 with mean number of sessions was 37.2 ± 14.9. Histopathological examination of the specimens showed that 85% of patients had evidence of chronic oesophagitis (group A) in the form of basal cell hyperplasia, hyperkeratosis and subepithelial fibrosis. Thirteen percent of the patients had evidence of reactive atypia (group B) in the form of severe neutrophilic intraepithelial inflammatory cellular infiltration, and 2 patients (2%) had mild squamous dysplasia (group C); we rebiopsied these two patients 6 mo after the initial pathological assessment, guided by chromoendoscopy by Lugol's iodine. CONCLUSION: The histopathology of oesophageal mucosal biopsies in post-corrosive patients demonstrates evidence of chronic oesophagitis, intraepithelial inflammatory cellular infiltration and dysplasia. Dysplasia is one of the complications of post-corrosive oesophageal stricture.

Is sofosbuvir/ledipasvir safe for the hearts of children with hepatitis C virus?

BACKGROUND: Symptomatic bradycardia has been reported in adults treated for chronic hepatitis C using sofosbuvir based regimens. AIM: We studied the cardiac safety of sofosbuvir/ledipasvir in Egyptian children, treated for chronic hepatitis C. METHODS: The study included 40 hepatitis C virus infected children and adolescents 12-17 years old, using the combination of sofosbuvir (400 mg)/ledipasvir (90 mg) in a single oral tablet (Harvoni) taken daily for 12 weeks. All subjects underwent a baseline standard 12-lead surface Electrocardiography that was repeated at 4 and 12 weeks of therapy. Electrocardiography parameters (Heart Rate, RR interval, PR interval, QRS, QT interval, corrected QT interval, QT dispersion, JT interval, corrected JT interval, JT dispersion, Tpeak-Tend interval) were compared at the 3 different time points during antiviral therapy. RESULTS: No symptoms related to the cardiovascular system were reported during treatment. There were no cases of symptomatic bradycardia/syncope. Heart rate was noted to be significantly lower and RR and QT intervals were significantly longer in the baseline electrocardiography. Heart rate was significantly lower and RR interval was significantly longer in patients with higher viral load. CONCLUSION: No adverse cardiovascular events were observed in this group of HCV infected children and adolescents treated with sofosbuvir/ledipasvir. None of the patients developed bradyarrhythmias during treatment.

Gastric antral vascular ectasia in portal hypertensive children: Endoscopic band ligation versus argon plasma coagulation.

BACKGROUND/PURPOSE: Gastric antral vascular ectasia (GAVE) can cause recurrent bleeding and chronic anemia in children with portal hypertension (PHT). We aimed to evaluate the efficacy of EBL in comparison to argon plasma coagulation (APC) in children with PHT, bleeding from GAVE. METHODS: This prospective comparative study included 40 children with PHT who presented with nonvariceal GIT bleeding from GAVE. Patients were divided into 2 groups, each including 20 cases: one group was managed with APC and the other with EBL. Endoscopy was repeated every 3-4 weeks until complete ablation of GAVE. Patients were reevaluated earlier in the event of recurrence of bleeding or in case of severe anemia necessitating blood transfusion. A follow-up endoscopy was done 6 months after the last APC or EBL session. RESULTS: The ages ranged between 2 and 16 years. The EBL group required a significantly lower number of sessions for complete obliteration of the lesions (1.85 ±â€¯0.81) as compared to APC group (4.15 ±â€¯1.22), p < 0.05. EBL was superior to APC as regards shorter procedure time (p = 0.001), lower blood transfusion requirement (p < 0.05), less hospitalization (p < 0.05) and significantly lower recurrence rate of GAVE after 6 months of follow up (p = 0.01) CONCLUSIONS: EBL is more effective and time saving when compared to APC in treatment of bleeding from GAVE in children. LEVELS OF EVIDENCE: Treatment study, Level II (prospective comparative study).

Paediatric chronic hepatitis B virus infection: are children too tolerant to treat?

AIM: Guidelines for managing the hepatitis B (HB) virus infection in children are still evolving. We aimed to assess the eligibility of children with HB virus infections for treatment based on the current guidelines. METHODS: This observational study took place in 2016 and focused on children with isolated chronic HB infections, who attended the paediatric hepatology units at two centres in Egypt. We recruited all treatment-naïve children aged one year to 18 years who had completed at least 12 months of follow-up. RESULTS: The study comprised 103 children aged between 1.5-18 years. Of these, 51 (50%) had the HB e antigen-positive chronic infection, 28 (27%) had the HB-negative chronic infection, 11 (11%) had the HB e antigen-positive chronic hepatitis and none had the HB e antigen-negative chronic hepatitis. The remaining 13 (12%) children did not fulfil the criteria for chronic HB definitions. Only two of the children were candidates for treatment: both had HB e antigen-positive chronic hepatitis and had undergone liver biopsies. CONCLUSION: Only two of the 103 children with chronic HB were eligible for treatment according to the current guidelines and every measure should be taken to prevent the HB virus infection in children.

Helicobacter pylori among symptomatic Egyptian children: prevalence, risk factors, and effect on growth.

AIM: This study was carried out to determine the prevalence and predictors of Helicobacter pylori (H. pylori) infection among symptomatic children and the effect on growth. METHODS: A cross-sectional study was conducted in the Outpatient Clinics of the Gastroenterology Unit of the Pediatric Hospital, Cairo University. A total of 630 children complaining of any symptoms or signs suspicious of H. pylori infection were enrolled. Weight and height were measured for each child, and the standard deviation scores (Z-scores) for weight-for-age (WAZ), weight-for-height (WHZ), and height-for-age (HAZ) were calculated. H. pylori was diagnosed using a stool antigen test. RESULTS: The overall prevalence of infection was 64.6%. Socio-demographic variables significantly associated with H. pylori were residence in Upper Egypt (P = 0.013) and rural areas (P = 0.004), illiteracy of mothers (P = 0.017), household crowding index ≥ 3 (P = 0.011), absence of pure water supply (P = 0.005), and eating from street vendors (P < 0.001). Values of WAZ [median, interquartile range (IQR) in infected = - 1.3(- 2.7 to - 0.4) and non-infected = - 0.7(- 2.1 to - 0.1), P < 0.001], HAZ (P = 0.036), and WHZ (P = 0.005) were significantly lower in children infected with H. pylori. After performing a backward logistic regression analysis, eating from street vendors (OR = 1.879, 95% CI 1.346-2.625, P < 0.001), absence of pure water supply (OR = 1.725, 95% CI 1.162-2.561, P = 0.007), and overcrowding (OR = 1.547, 95% CI 1.100-2.177, P = 0.012) remained the significant predictors of H. pylori infection. CONCLUSION: A high prevalence of H. pylori infection among symptomatic children was detected. The extra-digestive effects of H. pylori were revealed in the form of affection of growth parameters and reduced levels of serum hemoglobin, iron, and ferritin.

Routine analysis of ascitic fluid for evidence of infection in children with chronic liver disease: Is it mandatory?

Ascitic fluid infection is a major cause of morbidity and mortality in cirrhotic patients, requiring early diagnosis and therapy. We aimed to determine predictors of ascitic fluid infection in children with chronic liver disease. The study included 45 children with chronic liver disease and ascites who underwent 66 paracentesis procedures. Full history taking and clinical examination of all patients were obtained including fever, abdominal pain and tenderness and respiratory distress. Investigations included: complete blood count, C-reactive protein, full liver function tests, ascitic fluid biochemical analysis, cell count and culture. Our results showed that patients' ages ranged between 3 months to 12 years. Prevalence of ascitic fluid infection was 33.3%. Gram-positive bacteria were identified in six cases, and Gram-negative bacteria in five. Fever and abdominal pain were significantly more associated with infected ascites (p value = 0.004, 0.006). Patients with ascitic fluid infection had statistically significant elevated absolute neutrophilic count and C-reactive protein. Logistic regression analysis showed that fever, abdominal pain, elevated absolute neutrophilic count and positive C-reactive protein are independent predictors of ascitic fluid infection. Fever, elevated absolute neutrophilic count and positive C-reactive protein raise the probability of ascitic fluid infection by 3.88, 9.15 and 4.48 times respectively. The cut-off value for C-reactive protein for ascitic fluid infection was 7.2 with sensitivity 73% and specificity of 71%. In conclusion, prevalence of ascitic fluid infection in pediatric patients with chronic liver disease and ascites was 33.3%. Fever, abdominal pain, positive C-reactive protein and elevated absolute neutrophilic count are strong predictors of ascitic fluid infection. Therefore an empirical course of first-line antibiotics should be immediately started with presence of any of these predictors after performing ascitic fluid tapping for culture and sensitivity. In absence of these infection parameters, routine ascitic fluid analysis could be spared.

Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus-infected Children and Adolescents Treated With Sofosbuvir/Ledipasvir.

OBJECTIVES: Recently, direct acting antivirals (DAAs), sofosbuvir (SOF) combined with ledipasvir (LED), were approved for treatment of hepatitis C virus (HCV)-infected children 12 years of age and older or weighting at least 35 kg for all HCV genotypes. The aim of this study was to assess the safety and efficacy of SOF/LED in genotype 4 HCV-infected Egyptian children and adolescents. METHODS: This observational study included 40 consecutive HCV-infected children of age 12 to <18 years old or weighing >35 kg, both treatment-naive and treatment-experienced. All of the children were hepatitis B virus-negative and had normal renal functions and heart rate. Patients received oral, fixed-dose combination tablet of SOF/LED (400 mg SOF, 90 mg LED [Harvoni]) once daily for 12 weeks. Potential side effects were recorded at weeks 4, 8, and 12 weeks of treatment. The study primary outcome was sustained virological response 12 weeks (SVR12) after end-of-treatment. RESULTS: The study included 40 children and adolescents, 24 were boys (60%); their age ranged between 11.5 and 17.5 years (mean 13.9 ±â€Š1.5). Baseline viral load ranged between 9630 and 24,600,000 IU/mL. HCV RNA became negative in 39 patients (97.5%) at 4 weeks and in all patients (100%) at weeks 8, 12, and SVR12. Asthenia was the commonest side effect, reported in 52.5% followed by headache in 47.5%. CONCLUSIONS: Treatment with all-oral DAAs (SOF/LED) for 12 weeks was well tolerated in Egyptian children and adolescents infected with genotype 4 HCV, with 100% SVR12 and negligible side effects.

Prospective study of the effect of topical application of Mitomycin C in refractory pediatric caustic esophageal strictures.

BACKGROUND: Esophageal strictures resulting from caustic ingestion in children are usually difficult to be managed, and surgical replacement is usually required for cases refractory to frequent dilatation sessions. Topical Mitomycin C (MMC) has been recently used in the management of resistant strictures. We evaluated the efficacy of MMC application in treatment of long refractory caustic esophageal strictures. METHODS: This prospective study included 120 patients of both sexes with refractory caustic long esophageal strictures (> 3 cm in length). All patients were randomly divided into two equal groups using the research randomizer program (1:1 randomization), group I underwent endoscopic dilatation therapy only and group II underwent dilatation with topical application of MMC. Follow-up was done regularly by assessing the dysphagia score and patients were evaluated after 6 months of management. The procedure was repeated four times with 2-week intervals. Complete relieve of symptoms (dysphagia score = 0) was assessed after the follow-up period. RESULTS: The complete cure was detected in 81.6% of patients in the MMC group compared to only 40% in the first group, p-value < 0.0001. During the follow-up, the average sessions of dilatation needed in group II were 3.25 ± 2.78 compared to 6.25 ± 1.74 sessions in group I (p < 0.001). The mean cost of sessions in patients who showed symptomatic and endoscopic improvement was significantly lower in group II (272.2 ± 51 US$) when compared to group I (404 ± SD 55.7 US$). CONCLUSIONS: Cure rate was double in the MMC group. MMC application significantly improved symptoms and reduced both the number and frequency of dilatations to alleviate dysphagia in patients with refractory caustic esophageal strictures and hence reduced the cost of treatment.

Helicobacter pylori infection in children with portal hypertensive gastropathy.

BACKGROUND: Data about the association of Helicobacter pylori (H. pylori) and portal hypertensive gastropathy (PHG) are scarce in children. The present study aimed to fill the knowledge gap in this area. METHODS: The prevalence of H. pylori infection was studied in a group of infants and children with PHG using rapid urease test and histological demonstration of H. pylori in gastric mucosal biopsy obtained by upper gastrointestinal endoscopy. The results were compared to a control group who underwent endoscopy for other indications mainly hematemesis and/or dyspepsia. RESULTS: H. pylori was equally prevalent in both groups (~60%). Children with PHG were significantly stunted in height, had significantly lower hemoglobin, platelets and serum iron. Severe PHG was associated with higher grade of esophageal varices. Within the group with PHG, H. pylori infection was associated with lower hemoglobin, serum iron and serum ferritin. Moderate to severe PHG was more associated with H. pylori infection. CONCLUSIONS: H. pylori infection was not more commonly associated with PHG, however, it might contribute to the severity of PHG. The synergistic effect of PHG and H. pylori infection might contribute to the retarded growth and iron deficiency status noted in this group.