Follow-up of chronic paediatric hepatitis C virus in a low-/middle-income country.

AIM: Follow-up of chronic hepatitis C virus (HCV) infection following Interferon (IFN) plus Ribavirin (RBV) or direct-acting antiviral (DAA) drug therapy in a cohort of paediatric outpatients as confirmed by a sustained virologic response (SVR). METHODS: This study included a cohort of 60 patients (6-18 years), divided into 2 groups: Group 1:21 patients who completed treatment with IFN/RBV. Group 2:39 treated with dual DAA therapy: 19 with Sofosbuvir/Ledipasvir (SOF/LED) and 20 with Sofosbuvir/Daclatasvir (SOF/DCV). RESULTS: Group 1:12 (57.1%) were cured, six were IFN/RBV treatment failure then subsequently treated with DAAs successfully, and three had liver transplants. IFN/RBV side effects were reported in all patients; however, fibrosis regressed in two cured patients. Group 2: all were cured. HCV RNA became negative in all DAAs-treated patients at weeks 2, 4 and 12 of treatment (100%) as well as SVR after 12 weeks (100%). Thirty patients reported no adverse side effects whereas only nine suffered minor side effects. CONCLUSIONS: In our cohort, SOF/LED therapy and SOF/DCV therapy were extremely safe and effective with 100% SVR and negligible short-term side effects. IFN/RBV therapy was much less effective (SVR 57.1%) and accompanied with short-term side effects. Fibrosis might stop and even regress with successful treatment.

A pilot study of the value of a stool color card as a diagnostic tool for extrahepatic biliary atresia at a single tertiary referral center in a low/middle income country.

BACKGROUND AND STUDY AIMS: Biliary atresia (BA) is a major cause of hepatic failure and consequent liver transplantation in pediatrics. If BA is not diagnosed early and the proper surgical intervention is not performed before the age of 3 months, the survival of the affected infant is significantly reduced. In 1994, a stool color card (SCC) for early detection of BA was developed and used in Japan, a country where the parents' socioeconomic and education levels are high. We aimed to assess the value of using the SCC as a screening tool for early diagnosis of BA at a tertiary referral center in Egypt (a low/middle-income country). PATIENTS AND METHODS: This prospective study enrolled 108 infants (56 females) aged 1 day to 4 months who presented with cholestasis to the Hepatology Unit of Cairo University Children's Hospital from January 2018 to August 2019. In most of our patients, the mothers were the main caregivers and the parents' socioeconomic and education levels were generally modest or low. We utilized the SCC courtesy of the Perinatal Services BC (Vancouver, Canada) with an Arabic translation. This SCC contains nine colored stool photos: the first six are ranked as abnormal colors and the last three are ranked as normal. RESULTS: We found that almost all referring physicians were unfamiliar with or unaware of the SCC concept. Twenty-six of our babies' mothers were illiterate and 36 had not completed their primary school education. In spite of this low education level, 43 mothers of babies who were finally confirmed to have BA correctly matched a stool color of BA on the SCC with their babies' stools, and 56 mothers of babies who were finally confirmed not to have BA correctly matched a stool color not of BA with their babies' stools. Only nine mothers made a wrong match. Therefore, the overall "lay" mothers' sensitivity and specificity in diagnosis of BA using the SCC were 93.48% (95% confidence interval [CI] 82.1%-98.63%) and 90.32% (95% CI 80.12%-96.37%), respectively. CONCLUSION: To the best of our knowledge, this is the first study reporting the use of the SCC (with an Arabic translation) in a low/middle-income country. Despite the referring physicians' unfamiliarity with the SCC and the mothers' relatively low education level at our center; SCC proved to be a simple, efficient, highly sensitive, specific, and applicable method for early diagnosis of BA. Therefore, SCC screening might increase mothers (as well as physicians) awareness of BA, and we recommend that it be more publicized and used as a mass neonatal screening tool in low/middle-income countries such as Egypt.

Paediatric hepatitis C virus infection and its treatment: Present, past, and future.

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the world. It is a challenging medico-social problem in the paediatric population. High HCV infection rates are reported in low and middle incomes countries. From the health economic point of view treatment of hepatitis C virus (HCV) with subsequent virus eradication is very effective as it eliminates the long-term sequelae of untreated or maltreated HCV. In this review we summarize the updates and highlight the historical approach of treatment of chronic HCV infection in children in the new era of directly acting antiviral (DAA) agents.

A clinical and immunological study of children with chronic hepatitis B virus infection.

AIM: To identify the clinical status and immunological profile of a cohort of children with chronic hepatitis B virus (HBV) infection to assess the short-term consequences of this infection. MATERIAL AND METHODS: This prospective case-control study included 30 children in the age range 1-15 years with positive HBsAg attending the Hepatology clinic of Alexandria University Children's Hospital. Twenty children received lamivudine (3 mg/kg, oral, once a day), and 10 children were lamivudine-resistant and received entecavir treatment (10-11 kg/0.3 mg to > 30 kg/1 mg). They were followed up every 3 months for 1 year. RESULTS: The study showed that 97% of the studied cases were discovered accidentally during routine investigations and only 3% presented by acute hepatitis. Ninety percent of them had family member infection with HBV, of which 70% were the mother. Eighty-seven percent of cases had no clinical signs, and only 13% of cases had hepatomegaly. All of the cases were HBsAg positive, 50% were HBeAg positive, 56.7% were HBeAb positive, 33.3% were HBcAb positive, and 100% were HBsAb negative. CONCLUSIONS: Most of children with HBV infection had associated family member infection and were accidentally discovered. Despite a marked decrease in HBV DNA level after treatment, there was no clearance of HBsAg and no HBsAb seroconversion. Screening for the HBsAb level in children with family members with HBV is recommended.

High-resolution anorectal manometry in children with functional constipation: a single-centre experience before and after treatment.

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 (p = 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 (p = 0.474 and p = 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.

Stool antigen detection versus 13C-urea breath test for non-invasive diagnosis of pediatric Helicobacter pylori infection in a limited resource setting.

INTRODUCTION: The prevalence of childhood infection with Helicobacter pylori 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 H. pylori stool antigen (HpSA) test with the 13C-urea breath test (13C-UBT) for the diagnosis of H. pylori 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 13C-UBT was used as the gold standard method for the diagnosis of H. pylori infection. RESULTS: The HpSA test detected H. pylori 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 13C-UBT (κ = 0.83, 95% CI: 68-97%, p < 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 H. pylori infections in children, though not as accurate as the 13C-UBT. It is more affordable, simpler to perform and more tolerable, representing a viable alternative, especially in developing countries.

An Initial Investigation of Do Not Resuscitate Acceptance in Egypt.

BACKGROUND: The aim of this work was to obtain objective data on the extent of knowledge and attitudes of the do not resuscitate (DNR) concept in an Egyptian urban setting. METHODS: This survey was conducted in Cairo, Egypt, using a structured questionnaire including 23 questions. Questions and questionnaire were developed from literature on DNR in the region and from pilot testing. RESULTS: A total of 461 persons participated. In all, 48 participants (10.4%, 95% confidence interval [CI]: 7.8-13.7) agreed on the concept of DNR, 226 (49%, 95% CI: 36.1-45.2) stated that it depends on the patient condition, and 187 (40.5%, 95% CI: 44.4-53.7) rejected DNR. Combining the first 2 categories, agree and depends on patient condition, over 60% of the respondents in effect supported DNR. Family members (35.6%, 95% CI: 31.4-40.3) and attending physicians (43.3%, 95% CI: 30.1-39.0) were selected over religious leaders (21%, 95% CI: 17.5-25.2) and representatives from state institutions (4.6%, 95% CI: 2.9-7.0) as to who should have authority for making a DNR decisions. DISCUSSION: These and additional results provide objective evidence that DNR will not be rejected outright in Egypt. More formal surveys are justified and will provide needed guidance for implementing DNR and related end-of-life medical care in Egypt.

Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis.

Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 µg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.

The burden of different pathogens in acute diarrhoeal episodes among a cohort of Egyptian children less than five years old.

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.

Patterns of hepatitis B infection in Egyptian children in the era of obligatory hepatitis B vaccination.

BACKGROUND AND STUDY AIMS: Mass compulsory HBV vaccination was applied in Egypt in 1992. The first dose of vaccine is administered at 2 months of age and routine screening of pregnant women for HBsAg is not applied. We aimed to evaluate the pattern of HBV infections after the implementation of HBV vaccination in Egyptian children. PATIENTS AND METHODS: Fifty-six children with HBV infection presented to the Paediatric Hepatology Unit, Cairo University Children's Hospital, over the period from 1992 to 2006. Their data were reviewed for risk factors, clinical, serological and histopathological profiles. These cases were followed-up for 6.3 ± 3.4 years. The data of those born before 1993 (did not receive HBV vaccine) (group I) was compared to those who received the vaccine (group II). RESULTS: Sixty percent of HBV infected cases were born before 1993. Comparison of data of both groups revealed: (1) A significant younger age of onset in group II (3.34 ± 3.31 years vs. 9.84 + 2.95 years; p ≤ 0.01). (2) Vertical transmission was a significant risk factor in group II. (3) Chronic hepatitis developed in almost half of cases in both groups but cirrhosis was diagnosed only in 4 cases (all from group I) (p=0.04). CONCLUSION: Vertically transmitted HBV infection is becoming an important risk factor for acquisition of HBV among children born after the era of mass vaccination in Egypt. Mass screening for HBsAg of pregnant Egyptian women and/or giving a birth dose of HBV vaccine is becoming mandatory with the increased incidence of vertical transmission.

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.

Propranolol safety profile in children.

Data regarding the use of propranolol in pediatrics are limited despite its widespread use in adults. Since 1984, Propranolol has been used for the prevention of portal hypertensive hemorrhage in pediatric patients. Recently it has been also used for the management of hemangiomas in addition to other indications. The purpose of this review is to evaluate safety and efficacy of propranolol use in the pediatric population, highlighting the most important reported side effects, warnings and precautions.

Value of duplex Doppler ultrasonography in non-invasive assessment of children with chronic liver disease.

AIM: to investigate the value of duplex Doppler ultrasonography (US) in the assessment of the hemodynamics of the portal and hepatic veins in a cohort of children with chronic liver disease (CLD) and to detect any relationship between the US changes, etiology and severity (or stage) of CLD. METHODS: we prospectively enrolled 25 children with biopsy-proven CLD. Thirteen had cirrhosis (aged 8.9 ± 2.0 years) and 12 had chronic hepatitis (aged 9.3 ± 2.3 years). Gray scale and color-coded duplex Doppler US were performed for all, as well as 30 healthy age and sex-matched controls. Findings were correlated with clinical, laboratory and histopathological characteristics. RESULTS: prominent caudate lobe was detected in 100% of cirrhotics, but none of the chronic hepatitis or controls. Thickened lesser omentum and loss of the triphasic waveform of the hepatic vein were present in 69.2% and 53.8% of cirrhotics vs 33.3% and 8.3% of chronic hepatitis respectively. Portal vein flow velocity was significantly lower (P < 0.0001) and the congestion index was significantly higher (P < 0.005) in both patient groups compared to controls. Child-Pugh's staging showed a positive correlation with both abnormal hepatic vein waveform and direction of portal blood flow; and a negative correlation with both hepatic and portal vein flow velocities. No correlation with the etiology of CLD could be detected. CONCLUSION: duplex Doppler added to grayscale US can detect significant morphologic and portal hemodynamic changes that correlate with the severity (stage) of CLD, but not with etiology.