Hanaa El-Karaksy

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.

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.

Viral etiologies of lower respiratory tract infections among Egyptian children under five years of age

BackgroundLower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method.MethodsWe collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses.ResultsTwo hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined.ConclusionsRSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.

Hepatitis C virus infection in Egyptian children: single centre experience

Summary.  The outcome of hepatitis C virus (HCV) infection acquired in childhood is uncertain because of the diversity of the epidemiological and clinical features of infection and disease. The aim of this study was to determine the outcome of HCV infection in 105 Egyptian children who tested positive for HCV antibody (anti‐HCV). The data of 105 anti‐HCV‐positive children presenting to the Pediatric Hepatology Unit, Cairo University Childrens Hospital, between 1995 and 2002, were retrospectively analysed for risk factors. Seventy‐four children with available polymerase chain reaction results were further analysed clinically, serologically and histologically. The age range was 1.3–22 years, with a mean of 11.2 ± 4.9 years. History of blood transfusion was found in 81 children (77%). HCV RNA was detected in 58.1% of 74 children. Persistently elevated alanine aminotransferase (ALT) levels were present in 40 patients (54.1%). Hepatitis B virus markers (HBsAg and/or anti‐HBc) were detected in 18 patients (24.3%). Twenty‐six of the 43 HCV RNA‐positive children underwent a diagnostic liver biopsy that showed chronic hepatitis in 19 patients (73.1%), cirrhosis in one case only (3.8%), and normal biopsy findings in seven children (26.9%). Blood transfusion remains a major risk of HCV transmission among Egyptian children. HCV infection is not always benign in the childhood period. ALT levels remain elevated in half of the children and histological abnormalities are detected in three quarters of HCV RNA‐positive cases.

Human fascioliasis in Egyptian children: successful treatment with triclabendazole.

Human fascioliasis (HF) is an increasingly recognized public health problem in Egypt. During the past two years we diagnosed HF in 40 Egyptian children. Diagnosis was based on some or all of the following criteria: fever, tender hepatomegaly and high eosinophilia (febrile eosinophilic syndrome), presence of Fasciola hepatica eggs in stools, and/or serodiagnosis using the indirect haemagglutination test (IHAT). Eight of the 40 children had failed to respond to previous treatment with praziquantel. All children were treated with triclabendazole in a dose of 10 mg/kg as a single oral dose. Within 2 months, 31 children (78 per cent) were cured as evidenced by clinical well-being, normalization of eosinophil counts, Fasciola antibody titres, and absence of Fasciola hepatica eggs in stools. The remaining nine cases achieved clinical and laboratory cure after a second dose of triclabendazole. No side-effects were encountered in any of the cases. We conclude that triclabendazole is an effective, well-tolerated, easy to administer drug that should be considered in HF.

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.

Strong Hepatitis C Virus (HCV)–specific Cell-mediated Immune Responses in the Absence of Viremia or Antibodies Among Uninfected Siblings of HCV Chronically Infected Children

BACKGROUND Cell-mediated immune (CMI) responses to hepatitis C virus (HCV) antigens in adults without seroconversion or viremia are biomarkers for prior transient infection. We investigated HCV-specific CMI responses in seronegative children living with HCV-infected siblings. METHODS Children 3-18 years of age living with HCV-infected siblings were screened for HCV antibodies and HCV RNA. Peripheral blood mononuclear cells (PBMCs) were evaluated for HCV-specific CMI responses by interferon γ (IFN-γ) enzyme-linked immunospot assay using 3 recombinant HCV protein antigens. Flow cytometry phenotypically characterized IFN-γ-secreting cells. RESULTS Forty-five seronegative children and 5 seropositive viremic siblings had functionally viable PBMCs. Among the 45 seronegative siblings, 15 (33.3%) had positive HCV-specific IFN-γ responses, and subsequent RNA testing revealed that 3 were viremic. Compared with the 5 seropositive viremic children, the median number of HCV-specific spot-forming units was significantly higher in the 12 seronegative aviremic children (P = .002) and in the 3 seronegative viremic children (P = .025). Flow cytometric analysis revealed that IFN-γ was synthesized mainly by CD4(+) T cells. CONCLUSION Strong HCV-specific CD4(+) T cell responses were detectable in higher frequency among seronegative, aviremic children compared with persistently infected siblings. Further studies are needed to determine whether these immune responses are protective against HCV infection.

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 Childrens 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.

Ultrasonography as a non-invasive tool for detection of nonalcoholic fatty liver disease in overweight/obese Egyptian children.

INTRODUCTION Liver biopsy, although a gold standard in diagnosis of nonalcoholic fatty liver disease (NAFLD), is an invasive and expensive tool. AIM To assess the diagnostic accuracy of abdominal ultrasound in detecting NAFLD among a group of overweight/obese children having one or more liver abnormality (clinical hepatomegaly, raised ALT or echogenic liver parenchyma by ultrasound). METHODS Seventy-eight overweight/obese children were referred to the Pediatric Hepatology Unit, Cairo University Pediatric Hospital, Egypt, for assessment for hepatic abnormalities. Out of the 78 children, 34 had one or more abnormality in the form of clinical hepatomegaly, raised alanine aminotransferase (ALT) and/or echogenic liver parenchyma by ultrasound. All 34 cases underwent liver biopsy for evaluation for NAFLD. RESULTS Histological NAFLD was detected in 15 cases; 8 simple steatosis and 7 nonalcoholic steatohepatitis (NASH). Sonographic evaluation of hepatic parenchymal echogenicity revealed: 11 with grade 1 echogenicity, 12 with grade 2 and 9 with grade 3 while only 2 had normal liver echopattern. Ultrasonography was 100% sensitive and 100% specific in detecting histological NAFLD, while the positive predictive value (PPV) was 47% and negative predictive value (NPV) was 11%. After consolidating the included children into 2 groups: the first including normal and grade 1 echogenicity and the second including grades 2 and 3, the sensitivity of ultrasonography in detecting histological NAFLD was still 100%, while negative predictive value increased to 100% with an accuracy of 82%. CONCLUSION We conclude that ultrasonography is an important non invasive tool in assessment for NAFLD. Normal or grade 1 hepatic echogenicity can soundly exclude histological NAFLD and obviates the need for liver biopsy.

Risk factors for hepatitis C virus acquisition and predictors of persistence among Egyptian children.

Hepatitis C virus (HCV) has a lower prevalence in children and knowledge is limited regarding the natural outcome of HCV infection in children.