Nabil Mohsen

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

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

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

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

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

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

Hereditary tyrosinemia type 1 from a single center in Egypt: clinical study of 22 cases

BackgroundHereditary tyrosinemia type 1 (HT1) is an increasingly recognized inborn error of metabolism among Egyptian children. This study was undertaken to define the presenting clinical, biochemical and imaging features and outcome of 2-(2-motrp-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC) therapy and liver transplantation in a cohort of Egyptian children diagnosed with HT1.MethodsThe study was carried out at the Pediatric Hepatology Unit at Cairo University Children’s Hospital. HT1 was diagnosed by quantification of succinylacetone (SA) in dry blood spots.ResultsTwenty-two patients were diagnosed with HT1 in a period of 3 years from August 2006 to July 2009. Infants with focal hepatic lesions and hepatomegaly (n=13) were younger at diagnosis than those with rickets (n=5) (median age: 3.25 vs. 10 months; P=0.05). Alpha fetoprotein was highly elevated in all children. Seven children died within a few weeks of diagnosis before therapy was initiated. Ten children were treated with NTBC. The response to NTBC treatment was apparent by a steep drop in serum alpha fetoprotein (AFP) and undetectable SA in urine within 2 months. Three children underwent living donor liver transplantation after treatment with NTBC for 10, 18 and 22 months respectively, despite adequate response to therapy because of financial issues. The explanted livers were all cirrhotic with no dysplasia or malignant transformation.ConclusionsFocal hepatic lesions are the commonest presentation of HT1 patients and they present at an earlier age than rickets. NTBC is effective but very expensive. Liver transplantation is still considered in HT1 patients.

Skin Iron Concentration: a Simple, Highly Sensitive Method for Iron Stores Evaluation in Thalassemia Patients

Iron overload is a potentially fatal complication in thalassemia patients. Accurate assessment of body iron is of utmost importance for these patients. The available methods for iron stores evaluation have limitations. We assessed biochemically the skin iron concentration (SIC) and determined the relation between the hepatic and skin iron level in thalassemia major patients to develop a simple, sensitive, quantitative measure of the body iron stores. Thirty-one cases with thalassemia major were assessed for iron overload. Liver and skin biopsies were performed for the patients and skin biopsies were taken from the 31 controls. The biopsies were subjected to biochemical assay of iron and histologic sections were examined. The SIC of the studied cases was significantly higher than that of the control group with a mean of 2.705 ± 1.14 and 0.275 ± 0.13 mg/g dry skin weight, respectively, p < 0.001. There was significant correlation between the SIC and the liver iron concentration (LIC) (r = 0.43, p = 0.01). The amount of liver iron is equivalent to [(3.5 × SIC) + 12.9]. With the use of this equation, we could reliably estimate an LIC value as high as 21.2 mg/g dry liver weight with a standard error of 4.07. Biochemical assay of the skin iron concentration is a reliable quantitative indicator of the body iron stores in patients with thalassemia major.

Gastric antral vascular ectasia in portal hypertensive children: Endoscopic band ligation versus argon plasma coagulation

BACKGROUND/PURPOSE Gastric antral vascular ectasia (GAVE) can cause recurrent bleeding and chronic anemia in children with portal hypertension (PHT). We aimed to evaluate the efficacy of EBL in comparison to argon plasma coagulation (APC) in children with PHT, bleeding from GAVE. METHODS This prospective comparative study included 40 children with PHT who presented with nonvariceal GIT bleeding from GAVE. Patients were divided into 2 groups, each including 20 cases: one group was managed with APC and the other with EBL. Endoscopy was repeated every 3-4 weeks until complete ablation of GAVE. Patients were reevaluated earlier in the event of recurrence of bleeding or in case of severe anemia necessitating blood transfusion. A follow-up endoscopy was done 6 months after the last APC or EBL session. RESULTS The ages ranged between 2 and 16 years. The EBL group required a significantly lower number of sessions for complete obliteration of the lesions (1.85 ± 0.81) as compared to APC group (4.15 ± 1.22), p < 0.05. EBL was superior to APC as regards shorter procedure time (p = 0.001), lower blood transfusion requirement (p < 0.05), less hospitalization (p < 0.05) and significantly lower recurrence rate of GAVE after 6 months of follow up (p = 0.01) CONCLUSIONS: EBL is more effective and time saving when compared to APC in treatment of bleeding from GAVE in children. LEVELS OF EVIDENCE Treatment study, Level II (prospective comparative study).

Copper concentrations in Egyptian infants with cholestasis: A single center study

BACKGROUND AND STUDY AIMS Hepatobiliary cholestatic disorders produce excess copper (Cu) retention in the liver, which is toxic and may cause hepatitis, fulminant hepatic failure, cirrhosis and death. In this study, we measured hepatic Cu and tested its correlation with serum Cu (S. Cu) and serum ceruloplasmin (S. ceruloplasmin) in cholestatic infants. PATIENTS AND METHODS 41 cholestatic infants were enrolled as cases and 11 healthy infants as control subjects. S. Cu and S. ceruloplasmin were done for all infants and hepatic Cu was measured in the liver specimen in cases. RESULTS Cases were 63.5% males with their age ranging between 1 and 7 months, while control subjects were 45.5% males with an age range between 3 and 18 months. Among cases, 41.5% had biliary atresia and 58.5% had intrahepatic cholestasis. Cholestatic infants had significantly higher levels of S. Cu and S. ceruloplasmin than control subjects and their hepatic Cu concentration was significantly higher than literature control. Infants with biliary atresia showed higher levels of Cu indices, with no statistical significance. Serum and hepatic Cu levels positively correlated with each other and with S. ceruloplasmin. Results of ROC curve showed that S. Cu was highly sensitive and specific for predicting hepatic Cu concentration at cut-off 181 μg/dl. CONCLUSION Serum and hepatic Cu concentrations were markedly elevated in patients with cholestasis and positively correlated with each other and with S. ceruloplasmin. S. Cu level can predict hepatic Cu concentration.

Haemophagocytic lymphohistiocytosis presenting as neonatal liver failure: A case series

BACKGROUND AND STUDY AIM Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome with liver involvement varying from mild dysfunction to severe fulminant failure. The aim of this study was to present a case series of four HLH patients presenting with acute liver failure (ALF) in the neonatal period. PATIENTS AND METHODS All four patients were neonates at the onset of symptoms. They presented to Cairo University Pediatric Hospital with ALF; they underwent prompt investigations including determination of ferritin, fibrinogen, and triglyceride levels as part of our ALF workup. Further investigations were tailored according to the associated clinical features and the results of preliminary investigations. RESULTS HLH was diagnosed according to HLH-2004 criteria. Three patients fulfilled at least five out of eight criteria. Fever, splenomegaly, elevated ferritin levels, and low fibrinogen levels were present in all patients. The fourth patient had a serum ferritin level >10,000ng/ml, favouring the diagnosis of HLH, despite fulfilling only four out of eight criteria. For three patients, positive consanguinity and previous sibling death were reported, suggesting a genetic aetiology of HLH. CONCLUSION ALF can be the presenting feature of HLH; thus, a high index of suspicion is necessary. Fever is a hallmark, especially in neonates. Diagnosis is important for this potentially treatable condition.

Erratum: 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 (Annals of Hematology (2004) vol. 83 (712-715))

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