Mortada El-Shabrawi

Recently, sofosbuvir and the fixed-dose combination of sofosbuvir/ledipasvir were approved for the treatment of chronic hepatitis C virus infection in adolescents, criteria being 12 years old and above or weighing at least 35 kg. Here we present the results of a pilot single cohort of 10 consecutive adolescent patients with chronic hepatitis C virus and treated with dual sofosbuvir/daclatasvir therapy for a response-tailored duration of 8 weeks for those who achieved very rapid virologic response (vRVR) and 12 weeks for those who did not. All patients achieved vRVR at week 2 and completed the shortened 8 weeks course. All patients (10/10) (100% [confidence interval 72.25-100%]) achieved sustained vRVR at week 12 post-treatment with good tolerability and no serious adverse events. These data could provide support to our suggested response-tailored protocol of dual therapy with sofosbuvir/daclatasvir in adolescents particularly for shortened duration in those who achieved vRVR. Further larger randomized controlled studies are recommended.

BACKGROUND: No available data on the use of sofosbuvir/ledipasvir combination in treatment of hepatitis C virus (HCV) infection in children 6- to 12- year old.

AIM: To assess the safety and efficacy of sofosbuvir plus ledipasvir in children 6- to 12- year old with chronic HCV genotype 4 infection.

METHODS: This is a pilot prospective single arm observational open-label multicentre study. A total of 20 consecutive eligible chronic HCV infected children, aged from 6- to 12- years were included in this study and treated with a fixed sofosbuvir/ledipasvir combination in half the adult dose (200/45 mg) once daily for 12 weeks. Laboratory tests including virological markers were measured at baseline, 2, 4, 8 and 12 weeks (end of treatment [EOT]), and 12 weeks after end of treatment for sustained virological response 12 (SVR12).

RESULTS: The intention-to-treat (ITT) SVR12 rate was 19/20 (95%; 95% CI: 76.4%-99.1%). SVR12 was not assessed in one patient who was lost to follow-up after showing viral negativity at the EOT12. All the remaining 19 patients (100%, 95% CI: 83.18%-100%) who completed the full protocol and follow-up visits achieved SVR12 with normal liver, haematological, and renal function tests and no side effects or fatalities.

CONCLUSIONS: This pilot study demonstrated that the fixed dose sofosbuvir/ledipasvir combination could be safe and effective treatment in children 6- to 12- years with chronic hepatitis C genotype 4 infection. Our pilot results might encourage larger and multicentre studies in this age group.

Introduction: The prevalence of childhood infection with is high, especially in developing countries. Non-invasive methods for detection of infection in children should be inexpensive, easy to perform, well tolerated and have a high diagnostic accuracy. We aimed to compare the reliability, specificity and sensitivity of the stool antigen (HpSA) test with the C-urea breath test (C-UBT) for the diagnosis of infection in a limited resource setting.

Material and methods: The stool samples of 60 symptomatic and dyspeptic children with a mean age of 7.2 ±3.7 years (2-15 years) were evaluated using the rapid One step HpSA test by lateral flow immunoassay. The C-UBT was used as the gold standard method for the diagnosis of infection.

Results: The HpSA test detected antigen in 34 out of 38 positive patients with 4 false-negatives (sensitivity 89.5%, 95% confidence interval (CI): 75.2-97.1%), while 21 patients had true-negative results and one false-positive (specificity 95.5%, 95% CI: 77.2-99.9%), with a strong measure of agreement between the HpSA test and the C-UBT (κ = 0.83, 95% CI: 68-97%, < 0.001). It had a positive predictive value of 97.1% (95% CI: 85.1-99.9%), a negative predictive value of 84% (95% CI: 63.9-95.5%) and an accuracy of 91.7%.

Conclusions: The rapid lateral flow HpSA test is a reliable method for the primary diagnosis of infections in children, though not as accurate as the C-UBT. It is more affordable, simpler to perform and more tolerable, representing a viable alternative, especially in developing countries.

Twenty-two scientists met at Krobielowice, Poland, to discuss the impact of the social environment, spatial proximity, migration, poverty, but also psychological factors such as body perception and satisfaction, and social stressors such as elite sports, and teenage pregnancies, on child and adolescent growth. The data analysis included linear mixed effects models with different random effects, Monte Carlo analyses, and network simulations. The work stressed the importance of the peer group, but also included historic material, some considerations about body proportions, and growth in chronic liver, and congenital heart disease.

Introduction: Constipation is a common disorder among children, and most of the cases are functional in aetiology. Few studies have reported the manometric data of normal and constipated children.

Aim: To evaluate the manometric parameters in children with functional constipation and to assess any possible changes in these parameters after treatment.

Material and methods: A prospective descriptive study was conducted at a single centre, enrolling 50 children diagnosed with functional constipation based on Rome IV criteria. Their age ranged from 6 to 14 years with a mean of 7.31 ±1.72 years. High-resolution manometry was performed on all children at the initial presentation and after six months of treatment.

Results: The studied children showed markedly abnormal rectal sensation parameters (increased first sensation, first urge, intense urge, and maximum tolerable volume) during rectal balloon distension. These parameters were even higher in children with stool incontinence ( = 0.005). Manometric data after 6 months of treatment showed that the resting and squeeze pressures were increased when compared to pre-treatment recordings; however, both were statistically insignificant ( = 0.474 and = 0.155, respectively). Abnormalities in rectal sensations and the manometric parameters reached near normal values following treatment.

Conclusions: Anorectal manometry is sensitive in predicting improvement in patient condition even before complete clinical cure, and it has a prognostic role in the management of childhood constipation. More research is still needed before recommending anorectal manometry as a routine diagnostic or prognostic tool in paediatric constipation management.

Recently, sofosbuvir and the fixed dose combination of sofosbuvir/ ledipasvir were approved for the treatment of chronic hepatitis C virus infection (HCV) in adolescents, 12 years old and above or weighing at least 35 kilograms. Here we present the results of a pilot single cohort of 10 consecutive adolescent patients with chronic HCV and treated with dual sofosbuvir/daclatasvir (SOF/DCV) therapy for a response-tailored duration of 8 weeks for those who achieved very rapid virologic response (vRVR) and 12 weeks for those who did not. All patients achieved vRVR at week 2 and completed the shortened 8 weeks course. All patients (10/10 (100% (CI: 72.25-100%)) achieved sustained virologic response at week 12 post-treatment (SVR12) with good tolerability and no serious adverse events. This data could provide support to our suggested response-tailored protocol of dual therapy with SOF/DCV in adolescents particularly for shortened duration in those who achieved vRVR. Further larger randomized controlled studies are recommended.

AIM: The aim of the current study is to investigate the prevalence of familial Mediterranean fever gene (MEFV) mutations in a cohort of Egyptian children with inflammatory bowel disease (IBD), and to characterize familial Mediterranean fever (FMF)-IBD patients, helping better understanding of IBD pathogenesis.

METHODS: The study enrolled 17 patients with ulcerative colitis (UC), 15 with Crohn's disease(CD), 10 with indeterminate colitis (IC) and 33 healthy children as controls. All cases and controls were tested for 12 FMF gene mutations by reverse hybridization after multiplex polymerase chain reaction amplification and DNA sampling.

RESULTS: Eighty-eight percent of the IBD patients carried the mutations, with Sequence variant V627A being the commonest versus 42.4% of controls. No associations were found between MEFV gene mutations, and phenotypic characteristics of IBD patients.

CONCLUSION: IBD patients, in populations with a high background carrier rate of MEFV variants, should be screened for MEFV gene mutations, especially those diagnosed as indeterminate colitis. Testing larger numbers of healthy Egyptian children for MEFV gene mutation is important to further determine the allele frequency in Egypt.

AIM: The aim of the current study is to investigate the prevalence of familial Mediterranean fever gene (MEFV) mutations in a cohort of Egyptian children with inflammatory bowel disease (IBD), and to characterize familial Mediterranean fever (FMF)-IBD patients, helping better understanding of IBD pathogenesis.

METHODS: The study enrolled 17 patients with ulcerative colitis (UC), 15 with Crohn's disease(CD), 10 with indeterminate colitis (IC) and 33 healthy children as controls. All cases and controls were tested for 12 FMF gene mutations by reverse hybridization after multiplex polymerase chain reaction amplification and DNA sampling.

RESULTS: Eighty-eight percent of the IBD patients carried the mutations, with Sequence variant V627A being the commonest versus 42.4% of controls. No associations were found between MEFV gene mutations, and phenotypic characteristics of IBD patients.

CONCLUSION: IBD patients, in populations with a high background carrier rate of MEFV variants, should be screened for MEFV gene mutations, especially those diagnosed as indeterminate colitis. Testing larger numbers of healthy Egyptian children for MEFV gene mutation is important to further determine the allele frequency in Egypt.

Neural tube defects (NTDs) are a group of congenital malformations with worldwide distribution and complex etiopathogenesis. Folic acid plays a pivotal role in their prevention. We aimed to identify the protective effect of folic acid intake against NTDs and its dependence on different socioeconomic and environmental factors in a cohort of mothers in Egypt.A cross-sectional study was carried over a period of 12 months on mothers who gave birth to babies with NTDs (group 1) and a control group with healthy offsprings (group 2). Both groups completed 2 questionnaires: food frequency questionnaire targeting the daily folate intake, and socioeconomic status and medical history questionnaire.Both groups of mothers received folate <800 μg/day, recommended for pregnant women. A strong association was detected between NTDs and urban residency with medium educated mothers, with negative consanguinity, who had folate intake < 400 μg daily, and who had their food long cooked. Each of these factors separately had a limited impact to cause NTDs, but when present together they did augment each other. Interestingly enough is the role of fava bean, cauliflower, spinach, and mango in predisposing of NTDs in the presence of the above-mentioned factors.The protective effect of folic acid intake against NTDs may depend on the synergism of different socioeconomic and environmental factors (which differ from country to another). In Egypt, females especially the medium-educated who live in urban areas should be well-informed with the value of folate intake in the periconceptional period.

INTRODUCTION: Diarrhoea continues to cause significant morbidity in Egypt.

AIM: To determine the frequency and distribution of different enteropathogens in acute diarrhoeal episodes, utilising an expanded testing regimen, and to correlate clinical signs and symptoms associated with the detected pathogens.

MATERIAL AND METHODS: The case-control study enrolled 356 patients < 5 years old with acute diarrhoea and 356 age and sex-matched healthy controls. Both cases and controls underwent a full history and physical examination, and provided two rectal swab specimens and a stool sample. Laboratory analysis included stool culture, microscopy, and indirect methods.

RESULTS: Rotavirus was detected in 11% of patients. Enterotoxigenic Escherichia coli (ETEC), Campylobacter, Shigella, and Salmonella were detected in 7%, 3.7%, 1.1%, and 1.4% of patients, respectively; and in 11.1%, 3.1%, 0.6%, and 0.6% of controls, respectively, with no significant statistical difference. Cryptosporidium was detected in 3.9% of cases. Mixed infection was detected in 5.9% of cases and 0.9% of controls, with a significant difference (p < 0.001). No pathogen was detected in 66.3% of cases and in 83.5% of controls. Rotavirus infection was associated with recurrent vomiting, dehydration, and hospitalisation. Bacterial diarrhoea was associated with vomiting (52%) in ETEC infections, fever (80%) in Salmonella infections, mucus (100%) and blood (50%) in stools of Shigella infections, and convulsions (15%) in Campylobacter infections.

CONCLUSIONS: Rotavirus is a prominent cause of diarrhoea among Egyptian children. Despite utilising an expanded testing regimen, more work is still needed for identification of other enteropathogens that constitute other causative agents of diarrhoea.

Chronic viral hepatitis B and C infections are highly prevalent and create a substantial burden to healthcare systems globally. These two chronic infections are the cause of significant global morbidity and mortality with approximately 1 million annual deaths attributable to them and their sequelae. Children are vulnerable to both infections. The availability of new drugs and new therapeutic strategies are increasing the complexity and individualizing the management of children with viral hepatitis. Therefore, it is extremely important to educate and advise pediatricians concerning the new lines of treatment. More than 350 million persons worldwide are infected with HBV. Although its incidence has dramatically declined since the implementation of universal immunization programs in many countries, scores of children are still being infected each year. Despite its benign course, chronic hepatitis B (CHB) during childhood and adolescence, 3-5% and 0.01-0.03% of chronic carriers develop cirrhosis or hepatocellular carcinoma (HCC), respectively, before adulthood. Treatment of CHB in childhood has been hampered by the long delay in licensing new drugs for pediatric use. Safe and effective antiviral therapies are available in adults, but few are labeled for use in children, and an accurate selection of whom to treat and the identification of the right timing for treatment are needed to optimize response and reduce the risk of antiviral resistance. Although several guidelines on the management of adult patients with CHB have been published by major international societies, the clinical approach to infected children is still evolving, and is mostly based on the expert opinions. Standard interferon (IFN)-α is still the treatment of choice for most children with HBV infection. Licensing of highly-effective nucleoside/nucleotide analogues (NA) for older children and adolescents has opened new possibilities of treatment. However, the risk of emergence of drug resistant strains is a public health problem and a major long-term issue for young patients. Before starting a child on NAs, the risks of treatment should be carefully weighed against the possible benefits. As the management of special patient populations is problematic and not evidence-based, their referral to highly specialized centers is strongly recommended. The World Health Organization estimates that over 250 million people worldwide are chronically infected with HCV. In countries where adults have a high prevalence of HCV infection, an increased prevalence in children can also be expected. In Egypt, for example, approximately 1-2% of children are infected. The child infected with HCV must be over 2 years old in order to be treated by a licensed drug. The standard of care therapy is pegylated IFN-α plus ribavirin with success rates as similar in adults. The first-wave, first-generation oral direct acting anti-virals (DAAs) telaprevir and boceprevir were licensed by the FDA for use in HCV genotype 1 infection in adults in 2011. Telaprevir and boceprevir must be coadministered with pegylated IFN-α and ribavirin. Sofosbuvir, the second-wave DAA has been approved in adults in January 2014 and other DAAs are on the way of approval soon in adults. Some DAAs are being tested for children and the results are eagerly awaited.

BACKGROUND AND STUDY AIMS: Measuring serum superoxide dismutase (SOD) levels in infants and children having acute or chronic liver disease of different aetiologies, and correlating these levels with disease aetiology in an attempt to clarify the role of SOD as an antioxidant in these diseases.

PATIENTS AND METHODS: We prospectively enrolled 58 infants and children and divided them into four groups: Group I, 24 patients with surgical cholestasis; group II, 11 patients with medical cholestasis; group III, nine patients with autoimmune chronic hepatitis; and group IV, 14 patients with viral hepatitis. Forty healthy age- and sex-matched children served as controls. Serum SOD activity was measured in all patients and controls using spectrophotometry.

RESULTS: The level of SOD showed a statistically significant increase in patients with medical cholestasis compared to healthy controls (p<0.0001). SOD activity of other groups showed no significant difference compared to controls.

CONCLUSIONS: Significantly increased serum SOD in infants and children with medical cholestasis is probably consequent to its increase in liver tissue in response to the liberation of reactive oxygen species. This suggests that products of free radical reactions might be involved in the pathogenesis and/or progression of medical cholestasis, and that SOD might attempt to minimise the liver injury.

Juvenile systemic lupus erythematosus (JSLE) is a chronic autoimmune disease characterized by multisystem involvement and diverse clinical and serological manifestations. Clinically significant hepatic disease is generally regarded as unusual in JSLE, but many studies have showed that hepatic disease may be more common in SLE than was usually thought. Hepatic disease does not cause significant morbidity and mortality, but subclinical liver involvement is common. One of the hepatic disorders associated with JSLE is autoimmune hepatitis (AIH). The precise etiology of AIH and JSLE remains unknown, however both AIH and JSLE are associated with antinuclear antibody (ANA) and multisystem disease manifestations. A shared immunologic response and genetic predisposition were suggested. Recently, new approaches for treatment of SLE and recent patents that could develop into novel therapeutic agents in clinical management of SLE have been proposed. An array of promising new therapies is currently emerging or being developed including B-cell depletion therapies, agents targeting B-cell survival factors, blockade of T-cell co-stimulation and present review, we will also report the case of a 12-year old girl who developed JSLE four years after her preliminary diagnosis with AIH.

AIM: To identify possible maternal risk factors for hepatitis B virus (HBV) acquisition and assess the efficacy of immunoprophylaxis given to infants born to hepatitis B virus surface antigen (HBsAg) positive mothers.

METHODS: Screening of 2000 pregnant females was carried out using rapid test and confirmed by enzyme immunoassay. A questionnaire consisting of 20 questions about the possible risk factors for acquisition of HBV infection was filled for every pregnant HBsAg positive female in addition to at least 2 pregnant HBsAg negative females for each positive case. Infants of HBsAg positive women were offered passive and active immunoprophylaxis within the 1st 48 h after birth, in addition to 2nd and 3rd doses of HBV vaccine after 1 and 6 mo respectively. Infants were tested for HBsAg and hepatitis B surface antibodies (HBsAb) at six months of age.

RESULTS: HBsAg was confirmed positive in 1.2% of tested pregnant women. Risk factors significantly associated with HBV positivity were; history of injections (OR = 5.65), history of seeking medical advice in a clinic (OR = 7.02), history of hospitalization (OR = 6.82), history of surgery (OR = 4) and family history of hepatitis (OR = 3.89) (P < 0.05). Dropout rate was 28% for HBsAg women whose rapid test was not confirmed and could not be reached to provide immunoprophylaxis for thier newborns. Immunoprophylaxis failure was detected in only one newborn (3.7%) who tested positive for HBsAg at 6 mo of age; and vaccine failure (seronegative to HBsAb after 4 doses of the vaccine) was detected in another one (3.7%). The success rate of the immunoprophylaxis regimen was 92.6%.

CONCLUSION: This pilot study shows that a successful national program for prevention of perinatal transmission of HBV needs to be preceded by an awareness campaign to avoid a high dropout rate.

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.

Entomophthoromycosis is a rare fungal infection that may affect immunocompetent hosts; predominantly in tropical and subtropical regions. Recently, the importance of this emerging mycosis has increased and the scope of its manifestations has been expanded. These manifestations; however, may masquerade as other clinical entities. Prompt diagnosis of this infection requires a high index of suspicion. Although histopathological examination and cultures are the gold standard diagnostic tools; molecular diagnosis is now available and started to play an important role. The cornerstone treatment is prolonged anti-fungal therapy along with surgical debridement. More awareness of this mycosis is warranted for definitive diagnosis and implementation of early proper therapeutic strategies.

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.

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