Mortada El-Shabrawi

Burden of pediatric hepatitis C

Hepatitis C virus (HCV) is a major health burden infecting 170-210 million people worldwide. Additional 3-4 millions are newly-infected annually. Prevalence of pediatric infection varies from 0.05%-0.36% in the United States and Europe; up to 1.8%-5.8% in some developing countries. The highest prevalence occurs in Egypt, sub-Saharan Africa, Amazon basin and Mongolia. HCV has been present in some populations for several centuries, notably genotypes 1 and 2 in West Africa. Parenteral anti-schistosomal therapy practiced in the 1960s until the early 1980s had spread HCV infection throughout Egypt. Parenteral acquisition of HCV remains a major route for infection among Egyptian children. Insufficient screening of transfusions, unsterilized injection equipment and re-used needles and syringes continue to be major routes of HCV transmission in developing countries, whereas vertical transmission and adolescent high-risk behaviors (e.g., injection drug abuse) are the major routes in developed countries. The risk of vertical transmission from an infected mother to her unborn/newborn infant is approximately 5%. Early stages of HCV infection in children do not lead to marked impairment in the quality of life nor to cognitive, behavioral or emotional dysfunction; however, caregiver stress and family system strain may occur. HCV slowly progresses to serious complications as cirrhosis (1%-2%) and hepatocellular carcinoma (HCC) especially in the presence of risk factors as hemolytic anemias, obesity, treated malignancy, and concomitant human immune deficiency and/or hepatitis B virus co-infection. HCV vaccine remains elusive to date. Understanding the immune mechanisms in patients who successfully cleared the infection is essential for vaccine development. The pediatric standard of care treatment consists of pegylated interferon-α 2a or b plus ribavirin for 24-48 wk. The new oral direct acting antivirals, approved for adults, need further evaluation in children. Sustained virologic response varies depending on the viral load, genotype, duration of infection, degree of aminotransferase elevation, adiposity and single nucleotide polymorphisms of interleukin (IL)-28B locus. The goals of treatment in individual patients are virus eradication, prevention of cirrhosis and HCC, and removing stigmatization; meanwhile the overall goal is decreasing the global burden of HCV. IL-28B polymorphisms have been also associated with spontaneous clearance of vertically acquired HCV infection. The worldwide economic burden of HCV for children, families and countries is estimated to be hundreds of millions of US dollars per year. The United States, alone, is estimated to spend 199-336 million dollars in screening, monitoring and treatment during one decade. The emotional burden of having an HCV infected child in a family is more difficult to estimate.

Prevalence of factor V Leiden mutation and other hereditary thrombophilic factors in Egyptian children with portal vein thrombosis: results of a single-center case-control study

No identifiable cause can be found in more than half of the cases of portal vein thrombosis (PVT). Our aim was to assess the prevalence of factor V Leiden mutation and other thrombophilic factors as risk factors in the development of PVT in the pediatric age group. From March 2001 to January 2002, 40 children with PVT were enrolled in the study, in addition to 20 age-matched and sex-matched controls. Protein C, protein S, antithrombin III, and activated protein C resistance (APCR) were assayed. Molecular study of factor II and factor V mutations was carried out. Of the patients, 25 had detectable hereditary thrombophilia (62.5%), 12 had factor V Leiden mutation (30%), 11 had protein C deficiency (27.5%), 6 had factor II mutation (15%), 1 had antithrombin III deficiency (2.5%), and none had protein S deficiency. Five children had concurrence of more than one defect. Factor V Leiden mutation is the most common hereditary thrombophilia associated with PVT and the relative risk of factor V Leiden mutation, as a cause of PVT, was six times more than in controls (odds ratio=6). Concurrence of more than one hereditary thrombophilic factor was seen in 12.5% of our patients. Circumstantial risk factors (neonatal sepsis, umbilical sepsis, umbilical catheterization) were not more significantly prevalent among patients with hereditary thrombophilia than among those with no detectable abnormalities in anticoagulation.

99mTechnetium-macroaggregated albumin perfusion lung scan versus contrast enhanced echocardiography in the diagnosis of the hepatopulmonary syndrome in children with chronic liver disease.

Background and aims The hepatopulmonary syndrome (HPS) is a triad of advanced chronic liver disease (CLD), arterial hypoxemia and intrapulmonary arteriovenous shunting in the absence of a primary cardiopulmonary disease. HPS has been more frequently reported in adults than in children with no data on its prevalence in children with CLD. The aim of this study was to detect the prevalence of the HPS in a cohort of children with CLD because of chronic hepatitis B and/or C virus infection, schistosomiasis as well as inborn metabolic errors. We also aimed to evaluate the role of 99mTechnetium labeled macroaggregated albumin (99mTc--MAA) perfusion lung scan versus contrast enhanced echocardiography (CEE) with intravenous injection of agitated saline in the diagnosis and quantification of intrapulmonary shunts and their relationship to important clinical and laboratory findings. Methods Forty Egyptian children (22 males) were investigated. Their ages ranged from 5 to 12 years (with a mean of 9.5 years). Twenty individuals proved to have cirrhosis. Results Blood gas determination revealed more significant arterial hypoxemia in cirrhotics than noncirrhotics both under room air and after breathing 100% oxygen for 15 mins. CEE showed comparable cardiac measurements in cirrhotic and noncirrhotic patients, and diagnosed intrapulmonary shunts in three hypoxemic cirrhotic patients; whereas 99mTc--MAAperfusion lung scan diagnosed shunts in seven patients (five of them cirrhotic). The presence of shunts was significantly correlated with the duration of CLD, clinical findings, presence of cirrhosis and porto-systemic collaterals. We calculated for each patient a shunt index (SI) by the formula: (activity outside thorax/activity outside plus inside thorax) 100; and an SI value of 0.278 was found to be a cutoff value for shunt detection. All patients with SI above this value had shunting associated with hypoxemia and all patients with SI below this value had no hypoxemia (specificity 100%). Conclusion Arterial hypoxemia and intrapulmonary shunts were diagnosed in 17.5% of this cohort of children with cirrhotic or noncirrhotic CLD representing the classic HPS. 99mTc--MAA perfusion lung scan was more sensitive than CEE in detection of intrapulmonary shunts. SI cutoff value of 0.278 was found to be highly specific for shunt detection and we recommend its validation in further studies.

Gastrointestinal basidiobolomycosis in children: an overlooked emerging infection?

Basidiobolus ranarum is a known cause of chronic subcutaneous zygomycosis. During the past decade, many cases have been reported with extracutaneous basidiobolomycosis. We aimed to review the medical literature on gastrointestinal basidiobolomycosis (GIB) as an emerging fungal infection causing a serious, and occasionally fatal, paediatric disease. We reviewed all reported cases of visceral basidiobolomycosis with special focus on the gastrointestinal involvement in children. Twenty-six cases of GIB have been reported worldwide, in 14 adults and 12 children. All cases presented with fever, abdominal pain with mass and high blood eosinophilia and were misdiagnosed as other chronic granulomatous diseases or malignancies. A few cases of retroperitoneal, pulmonary, nasal and disseminated basidiobolomycosis have also been reported. Basidiobolomycosis mostly affects young males as a subcutaneous infection. The visceral form of infection is rare. GIB has been scarcely reported in the medical literature, but recently it has been increasingly recognized. GIB poses diagnostic difficulties. Abdominal pain with mass and eosinophilia were present in all cases, highlighting the necessity of considering GIB in the differential diagnosis of this presentation. B. ranarum has been reported to cause disseminated fatal disease in both immune-competent and -compromised individuals. Culture is the gold standard for diagnosis, but the characteristic histopathological picture of chronic granulomas rich in eosinophils and the Splendore-Hoeppli phenomenon are the usual diagnostic tools. Surgery plus long courses of itraconazole treatment, up to 1 year, appear to be the best management options. GIB is an emerging infection that might lead to diagnostic confusion, morbidity and mortality. Diagnosis requires a high index of suspicion in the differential diagnosis of patients with fever, abdominal pain with mass and eosinophilia.

Gastrointestinal basidiobolomycosis: an emerging fungal infection causing bowel perforation in a child.

Basidiobolomycosis is an unusual fungal skin infection that rarely involves the gastrointestinal (GI) tract. We report a 10-year-old boy diagnosed as suffering GI basidiobolomycosis after being misdiagnosed first as suffering intestinal malignancy then schistosomiasis. The patient presented with fever, abdominal pain, vomiting, abdominal tenderness and rigidity with marked blood eosinophilia. Abdominal ultrasonographic and computed tomographic scans revealed a large caecal mass. Biopsy of the mass showed transmural granulomatous inflammation interpreted as schistosomal granuloma, ruling out lymphoma. The patients condition deteriorated despite anti-schistosomal therapy. Emergency surgery was then performed, and caecal perforation was found. The mass was excised; cultures were negative and histopathological examination was suggestive of schistosomal granuloma. The mass recurred 3 weeks post-operatively. Second-opinion histopathological examination diagnosed Basidiobolus ranarum infection. Treatment with itraconazole produced marked improvement, with diminution of the mass. B. ranarum was unequivocally identified in the archival formalin-fixed and paraffin-embedded (FFPE) tissue by PCR. This case emphasizes the need to consider GI basidiobolomycosis in children presenting with fever, abdominal mass and eosinophilia, especially those complicated by bowel perforation.

Celiac Disease in Children and Adolescents with Autoimmune Hepatitis: a Single-centre Experience

OBJECTIVES Celiac disease (CD) is increasingly reported from North Africa, including Egypt. Autoimmune hepatitis (AIH) is considered a high risk factor for CD. We aimed to investigate the frequency of CD diagnosis in AIH. METHODS We prospectively enrolled 26 AIH patients aged 3.5-21 (mean 9.98 ± 3.94) years and 20 healthy age- and sex-matched controls. Serodiagnosis of CD was based on the most sensitive tests namely immunoglobulin A (IgA) human tissue transglutaminase antibody (IgA-tTGA) by enzyme-linked immunosorbent assay and/or IgA endomysial antibody (IgA-EMA) by immunofluoresence and confirmed the diagnosis by upper gastrointestinal endoscopy and histo-pathological findings in jejunal biopsy. RESULTS IgA-EMA was positive in four patients (15.4%), whereas IgA-tTGA was positive in two of them (7.7%). Histopathology was confirmatory in three (11.5%) seropositive patients. CONCLUSION The high prevalence (11.5%) of CD among Egyptian children with AIH indicates that CD exists in high-risk groups in our region and must be carefully looked into.

Human Fascioliasis: Clinical Features and Diagnostic Difficulties in Egyptian Children

Human fascioliasis (HF) has been reported in children worldwide and occasionally from Egypt. In the past 7 years we diagnosed 16 children aged 3.5-11 years (mean age: 6.5 years), 13 of them were boys, as HF. They were referred to Cairo University, Paediatric Hospital (CUPH), with pyrexia of undetermined origin (PUO) and abdominal pain. Diagnosis was based on high peripheral blood eosinophilia (14-82 per cent) in all patients along with Fasciola hepatica egg detection on direct stool smear in three or stool concentration in four, antibody detection by indirect haemagglutination test (IHAT) in seven egg-negative patients and ultrasonographic detection of hepatic and/or biliary lesions of HF in two egg-negative patients. Percutaneous liver biopsy confirmed the diagnosis of an eosinophilic abscess (parasitic granuloma) in 12 of 13 patients. Therefore, HF does occur in Egyptian children and its diagnosis needs a high index of suspicion supported by stool microscopy, serology, imaging procedures, and probably liver biopsy.

Outpatient blind percutaneous liver biopsy in infants and children: Is it safe?

Background/Aim: We aim to investigate the safety of outpatient blind percutaneous liver biopsy (BPLB) in infants and children with chronic liver disease (CLD). Patients and Methods: BPLB was performed as an outpatient procedure using the aspiration Menghini technique in 80 infants and children, aged 2 months to 14 yrs, for diagnosis of their CLD. Patients were divided into three groups: Group 1 (<1 year), group 2 (1–6 yrs), and group 3 (6–14 yrs). The vital signs were closely monitored 1 hr before biopsy, and then 1, 2, 6, and 24 hrs after biopsy. Twenty-four hours pre- and post-biopsy complete blood counts, liver enzymes, prothrombin time (PT), and abdominal ultrasonography, searching for a biopsy-induced hematoma, were done for all patients. Results: No mortality or major morbidities were encountered after BPLB. The rate of minor complications was 17.5% including irritability or “pain” requiring analgesia in 10%, mild fever in 5%, and drowsiness for >6 hrs due to oversedation in 2.5%. There was a statistically significant rise in the 1-hr post-biopsy mean heart and respiratory rates, but the rise was non-significant at 6 and 24 hrs except for group 2 where heart rate and respiratory rates significantly dropped at 24 hrs. No statistically significant difference was noted between the mean pre-biopsy and the 1, 6, and 24-hrs post-biopsy values of blood pressure in all groups. The 24-hrs post-biopsy mean hemoglobin and hematocrit showed a significant decrease, while the 24-hrs post-biopsy mean total leucocyte and platelet counts showed non-significant changes. The 24-hrs post-biopsy mean liver enzymes were non-significantly changed except the 24-hrs post-biopsy mean PT which was found to be significantly prolonged, for a yet unknown reason(s). Conclusions: Outpatient BPLB performed by the Menghini technique is safe and well tolerated even in infants and young children. Frequent, close monitoring of patients is strongly recommended to achieve optimal patient safety and avoid potential complications.

Predictive accuracy of serum hyaluronic acid as a non-invasive marker of fibrosis in a cohort of multi-transfused Egyptian children with β-thalassaemia major

BACKGROUND AND STUDY AIM Liver disease remains a major cause of morbidity and mortality in patients with β-thalassaemia major (β-TM); therefore, its identification at an early stage is of great significance. Serum hyaluronic acid (HA) is considered as a non-invasive marker that appears early before pathological changes occur. We aim to determine the predictive accuracy of HA in detecting and staging hepatic fibrosis in β-TM patients. PATIENTS AND METHODS 30 Egyptian children with β-TM, and 15 age and sex-matched controls were studied. All had abdominal ultrasonography (US), measurement of serum amino-transferases (ALT, AST); hepatitis C, B and human immunodeficiency viruses (HCV, HBV, HIV) sero-markers, serum ferritin and HA. Liver biopsy was done for patients and fibrosis was scaled using Metavir scoring system and liver iron concentration (LIC) was measured. RESULTS Twenty patients (67.7%) had sero-markers of HCV, none had HBV or HIV. Serum HA was significantly higher in patients (90.78±28.79 ng/ml) compared to controls (21.1±13.24 ng/ml) with p<0.05. No difference between HCV infected and non-infected patients was detected. Positive significant correlation was detected between serum HA and stages of fibrosis by histopathology and US. No correlation was found between serum HA and age, sex, weight, height, haemoglobin level, platelet count, AST, serum ferritin, necro-inflammatory grade, and LIC. CONCLUSIONS Serum HA is a valuable non-invasive marker that may contribute to the assessment of liver fibrosis in multi-transfused children and adolescents with β-TM, irrespective of concomitant HCV infection.

Diagnosis of gastrointestinal basidiobolomycosis: a mini‐review

Basidiobolus ranarum (Entomophthoromycotina) very rarely affects the gastrointestinal (GI) tract. To date, reported paediatric GI basidiobolomycosis cases are 27 worldwide; 19 from Saudi Arabia and 8 from other parts of the world. Often these cases present a diagnostic dilemma, are prone to misdiagnosis and lack of disease confirmation by proper molecular methodologies. The fungal mass removed by surgery is usually sent for conciliar histopathology, isolation by fungal cultures and final molecular testing for basidiobolomycosis. The incidence of basidiobolomycoses, their predisposing factors and the molecular diagnosis of the fungus causing the disease in combination with a phylogenetic framework are reviewed.