Improvement in Liver Stiffness in Pediatric Patients with Hepatitis C Virus after Treatment with Direct Acting Antivirals.

OBJECTIVES: To assess the degree of liver stiffness using transient elastography in Egyptian children infected with hepatitis C virus (HCV) at baseline and 1 year after achievement of sustained virologic response (SVR) with direct acting antivirals. STUDY DESIGN: This prospective study included children infected with HCV who received treatment with sofosbuvir/ledipasvir and achieved SVR. At baseline and 1 year after achievement of SVR, the extent of hepatic fibrosis was assessed by transient elastography using FibroScan to measure liver stiffness, in addition to noninvasive markers including aspartate aminotransferase/platelet ratio index (APRI) and fibrosis-4 (FIB-4) index. RESULTS: The study included 23 cases that had variable degrees of fibrosis at baseline; their ages ranged between 10 and 18 years. At baseline, 13 patients had F1; 3 patients had F1-F2; 1 patient had F2; 3 patients had F3; 2 had F3-F4; and 2 patients with F4. One year after achievement of SVR, there was a statistically significant improvement in liver stiffness, APRI, and FIB-4 index (P = .03, <.001, .02, respectively). In 13 patients (56.5%), the liver stiffness improved; in 7 patients, it was stationary; and the remaining 3 patients showed mild increase in liver stiffness that was, however, associated with improvement in APRI and FIB-4 index. Comorbid conditions and previous treatment with interferon were not associated with increased liver stiffness 1 year after SVR. CONCLUSIONS: Egyptian children infected with HCV genotype 4 achieved significant regression in liver stiffness after treatment with direct acting antivirals.

Secondary hepatic dysfunction in pediatric intensive care unit: Risk factors and outcome.

BACKGROUND: Hepatic dysfunction has a significant role in intensive care unit patients' morbidity and mortality. AIM: To study the frequency, risk factors and outcome of secondary hepatic dysfunction in children admitted to the pediatric intensive care unit. METHODS: Secondary hepatic dysfunction was defined as the development of abnormal liver functions in a patient without a previous liver disease during intensive care unit stay. The following data were collected: age, gender, indication of admission, type of organ dysfunction, presence of sepsis, shock, need for inotropic support or mechanical ventilation, administered medications and mortality scores. Liver function tests were done on admission and at 7-day intervals. RESULTS: One hundred and fifty-one patients were included. Forty-three (28.5%) acquired secondary hepatic dysfunction. Several risk factors were significantly associated with secondary hepatic dysfunction: sepsis (p<0.001), cardiovascular events (p<0.001), hypoxia (p<0.001), number of administered antibiotics (P = 0.001), use of inotropes (p<0.001) and mechanical ventilation (p = 0.001). Secondary hepatic dysfunction was significantly associated with mortality and prolonged length of stay (P=<0.001). CONCLUSION: Secondary hepatic dysfunction is a common finding in the pediatric intensive care unit. Sepsis, cardiovascular events and hypoxia, are the main risk factors for secondary hepatic dysfunction. Mortality and prolonged length of stay are strongly related to secondary hepatic dysfunction.

Causes of secondary non-alcoholic fatty liver disease in non-obese children below 10 years.

This study aimed to detect etiologies and histopathological features of non-alcoholic fatty liver disease (NAFLD) in Egyptian children < 10 years from hepatologist perspectives. Infants and children below 10 years of age with biopsy-proven fatty liver over a 6-year period were included. NAFLD activity score was used to detect the presence of non-alcoholic steatohepatitis (NASH). The study included 66 cases whose age ranged between 5 months and 10 years. Transaminases were elevated in 60% patients. Glycogen storage disease (GSD) was the most common diagnosis (33.3%) followed by hepatitis C virus (HCV) (10.6%) and Chanarin-Dorfman syndrome (CDS) (9.1%). The cause of steatosis could not be identified in 28.8% of cases. There was a higher prevalence of secondary causes of NAFLD in patients < 10 years. Liver histopathological examination revealed preserved lobular architecture in 75.7% with minimal-to-mild fibrosis in 79%. Steatosis was macrovesicular in all specimens (severe steatosis in 39.4%). Four patients had NASH. Higher degree of steatosis was associated with more severe fibrosis (P = 0.01).Conclusion: GSD was the commonest cause of secondary NAFLD in Egyptian children < 10 years followed by HCV and CDS with higher degrees of steatosis in younger patients. The degree of fibrosis was significantly related to the degree of steatosis.What is Known:• Primary non-alcoholic fatty liver disease (NAFLD) is rare in children aged less than 10 years.• Secondary causes of NAFLD should be considered in patients who do not have traditional risk factors.What is New:• Glycogen storage disease, hepatitis C virus, and Chanarin-Dorfman syndrome are the commonest causes of secondary NAFLD in Egyptian children (< 10 years) with higher degrees of steatosis in younger patients.• The degree of liver fibrosis is significantly related to the degree of steatosis.

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.

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.

Safety and Efficacy of Combined Treatment with Pegylated Interferon Alpha-2b and Ribavirin for HCV Genotype 4 in Children.

Combined treatment with pegylated interferon (PEG-IFN)-α2b and ribavirin (RBV) is the only currently approved treatment for hepatitis C virus (HCV) infection in children. The aim of this study was to assess the safety and efficacy of combined treatment with PEG-IFN-α2b and RBV in Egyptian children and adolescents with genotype 4 (GT4) HCV infection. The study included 66 patients (3-17 years of age), of both sexes, infected with HCV GT4, treated with PEG-IFN-α2b (60 µg/m(2)), subcutaneously once weekly plus RBV (15 mg/kg/day) in 2 divided oral doses. Efficacy was assessed by achievement of sustained virological response (SVR). Safety was assessed by questionnaires directed to the patients at specific intervals, growth assessment and laboratory tests. SVR was achieved in 28 patients (42.4%). Nonresponders had significantly commoner history of treated malignancies (P = 0.03), baseline lower absolute neutrophil count (ANC; P = 0.009), higher gamma glutamyl transpeptidase (GGT; P = 0.003), and higher viral load (P = 0.03). Fever was the most frequently reported side effect occurring in 98.5% of the patients followed by musculoskeletal symptoms. Neutropenia was observed in 36 patients (54.6%) and necessitated treatment discontinuation in 1 patient. Decline in both weight and height percentiles was observed in 70% of children who received the combined therapy for a total of 48 weeks. In conclusion, the currently available treatment for HCV GT4 in pediatric patients has modest SVR with numerous adverse events necessitating meticulous monitoring to optimize care of the patients. Side effects could be managed with dose modifications and specific treatment when necessary.

The value of different insulin resistance indices in assessment of non-alcoholic fatty liver disease in overweight/obese children.

OBJECTIVE: The aim of the present study was to determine the association between insulin resistance (IR) and both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in a group of Egyptian overweight/obese children and adolescents and to evaluate different IR indices in detection of NAFLD. PATIENTS AND METHODS: The study included 76 overweight/obese children aged 2-15 years; 52.6% were males. Laboratory analysis included fasting blood glucose, serum insulin, lipid profile, liver biochemical profile, and liver ultrasound. IR was calculated using the following indices; the homeostasis model assessment method (HOMA-IR), the quantitative insulin-sensitivity check index (QUICKI) and hepatic insulin sensitivity. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of MetS. Liver biopsy was done when medically indicated and accepted by parents. RESULTS: IR was detected in 43.4% and 34.2% by using QUICKI and HOMA, respectively. MetS was detected in 36.8% and NAFLD was detected in 45.5% among those performing liver biopsy. Cases with NAFLD had more frequent IR than children with normal histology. QUICKI showed significant difference between normal subjects and both steatosis and non-alcoholic steatohepatitis; while HOMA-IR was sensitive in cases with NASH only. MetS was present in 100% of patients with NASH and in 75% of those with steatosis and they were all obese. Patients with NASH had significantly higher ALT than those with normal histology. CONCLUSION: IR was significantly associated with NAFLD. QUICKI is considered more sensitive than HOMA-IR in differentiating simple steatosis from normal liver histology.

The effect of tailoring of cornstarch intake on stature in children with glycogen storage disease type III.

AIM: To determine the individual fasting tolerance for patients with glycogen storage disease type III (GSD III) and to assess their linear growth velocity after tailoring of dose intervals of oral uncooked cornstarch. PATIENTS AND METHODS: A prospective cohort study included 32 patients with GSD III aged 6 months-11.5 years (median: 3.3 years). The fasting tolerance of each patient was determined as the time interval between starch administration until the drop in blood glucose level was below 60 mg/dL. RESULTS: Some 27 patients (84.4%) developed hypoglycemia. The intervals between oral cornstarch administration were tailored for each child according to his/her individual fasting tolerance. After a 6-month follow up there was a significant reduction in seizure attacks (p<0.01) and liver size (p<0.01), but there was no statistically significant difference in liver transaminase and serum lactate levels. There was a significant improvement in height (p<0.01) and linear growth velocity (p<0.05) of these patients after at least a 12-month follow up. CONCLUSION: Adjusting the intervals between the cornstarch doses for each patient with GSD III, according to individual fasting tolerance test was very beneficial and resulted in improvement of the linear growth velocity and reduction in the frequency of hypoglycemic seizures as well as the size of the liver. Individual scheduling of cornstarch doses prevents complications in those who develop hypoglycemia at short intervals; it also allows some relaxation in schedule for those who can tolerate longer fasting hours to improve their appetite and prolong their uninterrupted sleep hours.

Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children.

AIM: To investigate the safety and efficacy of a Hansenula-derived PEGylated (polyethylene glycol) interferon (IFN)-alpha-2a (Reiferon Retard) plus ribavirin customized regimen in treatment-naïve and previously treated (non-responders and relapsers) Egyptian children with chronic hepatitis C infection. METHODS: Forty-six children with chronic hepatitis C virus (HCV) infection were selected from three tertiary pediatric hepatology centers. Clinical and laboratory evaluations were undertaken. Quantitative polymerase chain reaction (PCR) for HCV-RNA was performed before starting treatment, and again at 4, 12, 24, 48, 72 wk during treatment and 6 mo after treatment cessation. All patients were assigned to receive a weekly subcutaneous injection of PEG-IFN-alpha-2a plus daily oral ribavirin for 12 wk. Thirty-four patients were treatment-naïve and 12 had a previous treatment trial. Patients were then divided according to PCR results into two groups. Group I included patients who continued treatment on a weekly basis (7-d schedule), while group II included patients who continued treatment on a 5-d schedule. Patients from either group who were PCR-negative at week 48, but had at least one PCR-positive test during therapy, were assigned to have an extended treatment course up to 72 wk. The occurrence of adverse effects was assessed during treatment and follow up. The study was registered at www.ClinicalTrials.gov (NCT02027493). RESULTS: Only 11 out of 46 (23.9%) patients showed a sustained virological response (SVR), two patients were responders at the end of treatment; however, they were lost to follow up at 6 mo post treatment. Breakthrough was seen in 18 (39.1%) patients, one patient (2.17%) showed relapse and 14 (30.4%) were non-responders. Male gender, short duration of infection, low viral load, mild activity, and mild fibrosis were the factors related to a better response. On the other hand, patients with high viral load and absence of fibrosis failed to respond to treatment. Before treatment, liver transaminases were elevated. After commencing treatment, they were normalized in all patients at week 4 and were maintained normal in responders till the end of treatment, while they increased again significantly in non-responders (P = 0.007 and 0.003 at week 24 and 72 respectively). The 5-d schedule did not affect the response rate (1/17 had SVR). Treatment duration (whether 48 wk or extended course to 72 wk) gave similar response rates (9/36 vs 2/8 respectively; P = 0.49). Type of previous treatment (short acting IFN vs PEG-IFN) did not affect the response to retreatment. On the other hand, SVR was significantly higher in previous relapsers than in previous non-responders (P = 0.039). Only mild reversible adverse effects were observed and children tolerated the treatment well. CONCLUSION: Reiferon Retard plus ribavirin combined therapy was safe. Our customized regimen did not influence SVR rates. Further trials on larger numbers of patients are warranted.

Acute hemolytic anemia as an initial presentation of Wilson disease in children.

BACKGROUND: Wilson disease (WD) is an inherited disorder of copper metabolism. Hemolytic anemia in WD occurs in up to 17% of patients at some point during their illness. AIM: To screen for WD among children presenting with hemolytic anemia. METHODOLOGY: Twenty cases (mean age, 8.8 ± 3.9 y) with Coombs-negative hemolytic anemia, attending the hematology clinic of children hospital, Cairo University, were screened for WD by serum ceruloplasmin level, 24 hours urinary copper before and after D-penicillamine challenge test, and slit-lamp examination for detecting Kayser-Fleischer rings. RESULTS: No case had low ceruloplasmin, whereas bilateral Kayser-Fleischer rings was detected in 5% of our cases. Urinary copper was elevated in 5% before and in 40% after D-penicillamine challenge test. According to the scoring system used, 1 case had definite WD and 7 cases were likely to have WD. These 8 (40%) cases were referred to as group B. Group B had a significantly lower hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, and reticulocytes (P=0.04, 0.001, 0.04, and 0.04, respectively) and a significantly higher urinary copper after penicillamine (P=0.000) when compared with group A (unlikely WD). CONCLUSION: WD is not uncommon in children with hemolytic anemia after exclusion of other common causes.

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.

Prevalence of hepatitis C virus infection and human immunodeficiency virus in a cohort of Egyptian hemophiliac children.

BACKGROUND AND OBJECTIVE: The risk of blood-borne infections, especially hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection still remains in developing countries among children receiving blood products as hemophiliacs, but the risk is not known in Egypt. The objective of this study was to detect the prevalence of HCV and HIV infection among hemophiliac children to know the magnitude of the problem and determine potential risk factors. PATIENTS AND METHODS: This was a cross-sectional study conducted on 100 hemophiliac children that assessed the liver clinically and by laboratory tests. All children were screened for HCV and HIV antibodies by enzyme-linked immunosorbent assay. Those with positive HCV antibody titre were tested by polymerase chain reaction (HCV-PCR). RESULTS: Forty were positive for HCV antibodies with 19 children (47.5%) HCV-PCR positive as well. The mean age, average frequency of bleeds/year, dose of replacement therapy/year and alanine aminotransferase (ALT) levels were significantly high in HCV-antibody and PCR positive patients as compared to HCV antibody and PCR negative ones. None of our patients had clinical evidence of hepatic involvement or was co-infected with HIV. CONCLUSION: HIV infection does not appear to be a current health problem in Egyptian hemophiliac children though the prevalence of HCV infection is still high.

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.

A clinical study of Wilson's disease: The experience of a single Egyptian Paediatric Hepatology Unit.

BACKGROUND AND STUDY AIMS: Most paediatric patients with Wilson's disease (WD) present with hepatic manifestations, but some may have neurologic or psychiatric features. Our aim was to define the clinical, biochemical features and the outcome of therapy of a group of Egyptian children diagnosed with WD. PATIENTS AND METHODS: The study was carried out at the Paediatric Hepatology Unit at Cairo University Children's Hospital, Egypt; 54 patients were diagnosed with WD from 1996 to 2009. The diagnosis was based on low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge and/or the presence of Kayser-Fleischer (K-F) rings. RESULTS: The clinical presentation was as follows: hepatic presentation in 33 patients (61%), hepato-neurologic 3 (5.5%), neurologic 5 (9.3%) and presymptomatic 13 (24%). Twelve couples had more than one affected sib. Increased urinary copper concentrations before or after D-penicillamine challenge was found in all patients, low serum ceruloplasmin in 97% and K-F rings in 31.5%. All patients were treated with penicillamine and zinc sulphate except one presymptomatic case who was treated with zinc sulphate only. Three patients underwent liver transplantation and eight patients died after a median duration of treatment of 6 months (1-36). The hepatic symptoms improved with treatment but the neurological symptoms remained stationary. CONCLUSIONS: Clinical and biochemical assays remain the standard for diagnosis of WD. Penicillamine and zinc therapy can effectively treat WD with hepatic symptoms. Liver transplantation remains life saving for those with fulminant and end stage WD. Screening for presymptomatic sibs is of utmost importance.

Relation of serum levels of thrombopoietin to thrombocytopenia in extrahepatic portal vein obstruction versus cirrhotic children.

INTRODUCTION: In patients with portal hypertension, thrombocytopenia in cirrhotics and noncirrhotics is thought to be caused by sequestration and destruction of platelets within a large spleen, suppression of platelet production in the bone marrow, and decreased activity of the hematopoietic growth factor thrombopoietin (TPO). AIM: Determining the level of TPO in cirrhotic thrombocytopenic patients and correlate it to the degree of disease severity and platelet count. METHODS: A cross-sectional study conducted on 62 children; 25 cases with cirrhosis, 20 patients with extrahepatic portal vein obstruction (EHPVO), and 17 healthy age-matched and sex-matched controls. The severity of liver cirrhosis was graded according to the Child-Pugh classification. TPO was measured using the quantitative human TPO by enzyme-linked immunosorbant assay. RESULTS: Serum TPO levels were significantly lower in the cirrhotic group compared with both EHPVO patients and healthy controls (P=0.01 for each). Both of the Child-Pugh B and C cirrhotic cases had significantly lower TPO levels compared with Child A cases (P=0.003). We found a significant positive correlation between platelet count and serum TPO level (r=0.56, P=0.004) in the cirrhotic group but not in the EHPVO group (r=0.1, P>0.05). CONCLUSIONS: TPO underproduction contributes to thrombocytopenia in children with cirrhosis; whereas in children with EHPVO, TPO production is unaffected and thrombocytopenia is secondary to hypersplenism. TPO receptor agonists may be useful to improve platelet counts in the former group.

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 Children's 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.

The association of HLA class II DR B1 alleles with HCV infection in Egyptian children.

BACKGROUND AND STUDY AIMS: Human leucocyte antigens (HLA) class II appear to play an important role in the individual's immune response to viral infection. The aim of this study is to assess the relationship between HLA class II antigens with the clinical, laboratory and histopathological state of the liver in Egyptian children and adolescents with chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: The study included 46 chronically infected HCV children and adolescents without - hepatitis B virus (HBV) nor human immunodeficiency virus - (HIV). Their mean age was 10.4±4.23years (3-17). HLA-DRB typing was done by polymerase chain reaction (PCR) for the patients and 20 control subjects. Biochemical and haematological parameters were assessed as well as a liver biopsy was taken from the included patients. RESULTS: The most frequent alleles demonstrated among patients were DRB1∗03, DRB1∗04 and DRB1∗13 (45.6%, 39.1% and 26.1%), respectively. Analysis of DRB1 frequencies between patients and control revealed that DRB1*15 is significantly reduced among patients when compared with the control group (p<0.01). Patients possessing the allele DRB1*03 had significantly reduced platelet count (p=0.03), and this allele was presented to a greater extent in patients with minimal grade of inflammation. Patients with DRB1*04 had significantly low serum albumin (p=0.04) and patients with DRB1*13 had significantly high serum aspartate aminotransferase (AST) levels (p=0.05). CONCLUSION: In Egyptian HCV-infected children, special HLA patterns were found; HLA DRB1*03 was present in nearly half of the patients, while the frequency of HLA DRB1*15 was significantly reduced among the cases in comparison to the control subjects.

Impact of Giardia lamblia on growth, serum levels of zinc, copper, and iron in Egyptian children.

The aim of this study is to evaluate the serological levels of zinc, copper and iron in Giardia lamblia-infected children and to study the effect of giardiasis on their weight compared to controls. We studied 30 children, 1-10 years old, who attended the outpatient clinics of Cairo University Pediatric Hospital, with gastrointestinal complaints and diagnosed as having giardiasis by stools examination, they were enrolled as a study group. The control group consisted of 30 age- and sex-matched healthy children, free of gastrointestinal complaints and free of giardiasis. Serological levels of zinc, copper, and iron were measured by atomic absorption spectrophotometer. The infected group had significantly lower weight, serum iron, and zinc than controls (P = 0.035, <0.001, and <0.001 respectively) and 63.3% of patients infected with giardiasis were 1-5 years old. In the infected cases, 60% suffered from of abdominal pain, 50% from weight loss, and 40% had intermittent diarrhea. Infected cases with weight percentiles below the fifth had significantly lower serum iron than those with normal percentiles (>5th). In conclusion, most giardiasis-infected children were between 1 and 5 years, with significant affection of weight, abdominal pain, and/or intermittent diarrhea. Serum zinc and iron levels were significantly decreased in the infected group compared to control (P < 0.001).

Assessment of hepatic fibrosis in pediatric cases with hepatitis C virus in Egypt.

AIM: To assess hepatic fibrosis and factors associated with its progression in children with HCV infection. METHODS: At the Hepatology Unit, Cairo University Children's Hospital, a single liver biopsy was performed to 43 children with HCV infection after an informed consent between 1998-2004. Their mean age at liver biopsy was 8.67 +/- 4.3 years. RESULTS: Among the 43 patients' biopsies, 12 (27.9%) were having no fibrosis, 20 (46.5%) mild fibrosis and 11 (25.6%) moderate to severe fibrosis. The median time for development of fibrosis was estimated to be 5.5 years. Developing fibrosis was significantly associated with shorter duration from first detected ALT elevation to biopsy (12 mo vs 1.2 mo, P=0.015) and having higher levels of direct serum bilirubin (0.3 mg/dL vs 0.5 mg/dL, P=0.048). No association was found between fibrosis stage and the presence of co-morbid conditions (P=0.33). CONCLUSION: Hepatic fibrosis was present in 72.1% of children with HCV infection. The development of fibrosis was associated with higher levels of direct serum bilirubin. There was no significant association between fibrosis and age, duration of infection, risk factors, co-morbid conditions and most biochemical parameters.