Manal El-Hawary

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.

Hepatitis C virus infection in Egyptian children: single centre experience

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

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

BACKGROUND AND STUDY AIMS Most paediatric patients with Wilsons 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 Childrens 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.

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 Childrens 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.

Assessment of coagulation and fibrinolysis in children with chronic liver disease.

We aimed at assessing the coagulation profile and detecting early evidence of fibrinolysis in pediatric patients with chronic liver disease. Seventy-six patients (40 boys) with a mean age of 9.8 ± 3.4 years suffering from chronic liver disease were enrolled in this study. They were followed up in the Pediatric Hepatology Unit, Cairo University Childrens Hospital. Thirty healthy children were included as controls. Patients were classified etiologically into four groups: chronic viral hepatitis, autoimmune hepatitis, miscellaneous and cryptogenic groups. Investigations to detect coagulopathy were done for all patients and controls: prothrombin time (PT), activated partial thromboplastin time, fibrinogen, fibrinogen degradation products, and D-dimer and complete blood count. Liver functions were done for all patient groups. A significantly lower platelet count, prolonged prothrombin time, with prolonged aPTT time was detected in all patients compared with controls (P < 0.001). The fibrinogen level showed no significant difference between patients and controls. D-dimer level was significantly higher in the miscellaneous and cryptogenic groups when compared to other patient groups and control group (P < 0.001). Significantly higher D-dimer levels were detected in patients with liver cirrhosis of child class A and B compared with noncirrhotic and control groups (P < 0.001). D-dimer correlated positively with PT (r = 0.290, P = 0.003), and negatively with platelet count (r = −0.324, P = 0.001) and prothrombin concentration (r = −0.270, P = 0.018). Fibrinolytic activity, as evidenced by high D-dimer, was detected in pediatric patients with chronic liver disease particularly if cirrhotic.

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))

1. Yamada R, Antunes M, Cardoso S, Servidoni M, Hessel G (1999) Portal vein thrombosis in children: clinical and laboratory study of 26 cases. Arq Gastroenterol 36:49–53 2. Rosendaal FR (1997) Thrombosis in the young: epidemiology and risk factors. A focus on venous thrombosis. Thromb Haemost 78:1–6 3. Kim J, Lee Y, Kim S, Lee S, Lim M, Kim H (2001) Does umbilical vein catheterization lead to portal vein thrombosis? Prospective evaluation in 100 neonates. Radiology 219:645– 650 4. Gurgey A, Aslan D (2001) Outcome of non-catheter related thrombosis in children: influence of underlying or co-existing factors. J Pediatr Hematol Oncol 23:159–164 5. Ahuja V, Marwaha N, Chawla Y, Dilawari JB (1999) Coagulation abnormalities in idiopathic portal vein thrombosis. J Gastroenterol Hepatol 14:1210–1211 6. Voelkerding KY, Hither S, Strobl F, Wit LA, Sebastinin LV, Anderson M, Lutz CT (1996) Resistance to activated protein C: comparison of the three different PCR methods for detection of FV R506Q. Mol Diagn 1:297–304 7. Yachha SK, Srivastava A, Sharma BC, Khanduri A, Baijjal SS (1996) Therapeutic gastrointestinal endoscopy. Indian J Pediatr 63:633–639 8. Pinar A, Saenz R, Rebollo J, Gomez-Parra M, Carrasco F, Herrerias JM, Jimenez-Saenz M (1998) Portal and mesenteric vein thrombosis in a patient heterozygous for a mutation (Arg506-Gln) in the factor V gene (factor V Leiden). J Clin Gastroenterol 27:361–363 9. Chamouard P, Pencreach E, Maloisel F, Grunebaum L, Ardizzone JF, Meyer A, Gaub MP, Goetz J, Baumann R, Uring-Lambert B, Levy S, Dufour P, Hauptmann G, Oudet P (1999) Frequent factor II G20210A mutation in idiopathic portal vein thrombosis. Gastroenterology 116:144–148 10. Bombeli T, Basic A, Fehr J (2002) Prevalence of hereditary thrombophilia in patients with thrombosis in different venous systems. Am J Hematol 70:126–132 11. Heller C, Schobess R, Kurnik K, Junker R, Gunther G, Kreuz W, Nowak-Gottl U (2000) Abdominal venous thrombosis in neonates and infants: role of prothrombotic risk factors—a multicenter case-control study. For the Childhood Thrombophilia Study Group. Br J Haematol 111:534–539 12. Egesel T, Buyukasik Y, Dundar SV, Gurgey A, Kirazli S, Bayraktar Y (2000) The role of natural anticoagulant deficiencies and factor V Leiden in the development of idiopathic portal vein thrombosis. J Clin Gastroenterol 30:66– 71 13. Fisher NC, Wilde JT, Roper J, Elias E (2000) Deficiency of natural anticoagulant proteins C, S and antithrombin III in portal vein thrombosis: a secondary phenomenon? Gut 46:534– 539 14. Schobess R, Junker R, Auberger K, Munchow N, Burdach S, Nowak-Gottl U (1999) Factor V G1691A and prothrombin G20210A in childhood spontaneous venous thrombosis-evidence of an age-dependant thrombotic onset in carriers of factor V G1691A and prothrombin G20210A mutation. Eur J Pediatr 158 [Suppl 3]:S105–S108 15. Janssen HL, Meinardi JR, Vleggaard FP, Van Uum SH, Haagsma EB, van Der Meer FJ, van Hattum J, Chamuleau RA, Adang RP, Vandenbroucke JP, van Hoek B, Rosendaal FR (2000) Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd–Chiari syndrome and portal vein thrombosis: results of a case-control study. Blood 96:2364–2368 The online version of the original article can be found at http://dx. doi.org/10.1007/s00277-004-0921-4