clinical study of Wilson's disease: the experience of a single Egyptian paediatric hepatology unit

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. 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. 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. 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

Progression of disease in extra hepatic biliary atresia is associated with reduced total hepatic blood flow: descriptive results of a prospective pilot study

Hepatic fibrosis and cirrhosis develop progressively in extrahepatic biliary atresia despite timely surgical intervention. We aimed to study total hepatic blood flow [hepatic artery and portal vein flow] as a possible predictive factor of outcome of infants having biliary atresia who had underwent Kasai portoenterostomy. Twenty Infants having biliary atresia underwent colored and pulsed Doppler ultrasound studies. They were done before and 2-3 months after portoenterostomy. Hepatic artery, portal vein and single hepatic vein mean flow, mean diameter, mean velocity, hepatic arterial to portal venous flow ratio and total hepatic flow/kg were calculated and correlated to final outcome. The detected mean total hepatic flow and total hepatic flow/kg preoperatively was 685.5 +/- 296 ml/min and 147.1 +/- 51.4 ml/min/kg and post-operatively in those who became anicteric was 854.4 +/- 107 ml/min and 149.5 +/- 37.2 ml/min/kg, 539.2 +/- 337.7 ml/min and 112.1 +/- 78.6 ml/min/kg in those who developed chronic disease and in those who died was 157.6 +/- 79.6 and 30.9 +/- 16.1 ml/min/kg respectively. Unresolving cholestasis in infants having biliary atresia with poor outcome following portoenterostomy is associated with decreased post-operative total hepatic flow. Preoperative total hepatic flow did not correlate with postoperative total hepatic flow

Factors associated with fibrosis progression in HCV infected children in Egypt

This study aimed at identification of factors that could be associated with development of hepatic fibrosis in children with HCV infection. The study was carried out at the Pediatric Hepatology Unit, Cairo University Children's Hospital, Egypt. Liver biopsies were obtained from 43 children with HCV infection after having informed consent from their parents in the period "1995-2002". Their mean age at liver biopsy was and 8.67 +/- 4.3 years. Boys: girls ratio was 1.3:1. The results proved that, by examining the 43 patients' biopsies, 12 were having no fibrosis, 20 were having mild fibrosis and 11 were having 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 [P =0.015] and having higher levels of direct serum bilirubin [P Value=0.048]. Unexpectedly, development of fibrosis was slower in the group with co- morbid conditions compared to the group with no co-morbid conditions [P =0.04]. The development of hepatic fibrosis in children with HCV infection was associated with shorter duration of first detected ALT elevation to biopsy and higher direct serum bilirubin levels and it was progressing more slowly in the group having co-morbid conditions

EEG changes in liver glycogenoses: a cross-sectional study

Children with glycogen storage disease [GSD] suffer from hypoglycemia that is life long and needs frequent feedings and nocturnal intragastric infusions of solutions containing glucose or cornstarch, a regimen that is not possible for most of our followed up patients. The objective of this study was the evaluation of permanent EEG changes in children suffering from liver glycogenoses with attacks of hypoglycemia, hypoglycemic convulsions and those with euglycemia. In a cross-sectional study, 25 children suffering from liver GSD [with no current neurological symptoms] and 20 age and sex matched clinically free children [control group] underwent EEG studies. The results showed that 11 [44%] of the studied children were found to have nocturnal convulsions. Abnormal EEG studies were found in 79 children [76%]. One had a left temporal epileptic focus, 1 had increased slow activity, 7 had abnormal background symmetry and 16 [64%] had absent alpha rhythm in alert state EEG recording. The focal findings did not prove to correlate to hypoglycemia but rather to the level of direct bilirubin above 0.3mg% and total bilirubin above 1mg% [P=0.018%]. Colchicine intake and its prolonged use [>36 months] were associated with abnormal discharge [P=0.004 and respectively P=0.008].The absence of alpha rhythm was related to positive consanguinity [P=0.003] and was detected in children with other affected sib [P=0.000]

Conclusion: liver glycogenosis are associated with EEG changes. These changes were found to be attributable to familial, genetic factors and factors affecting the liver capacity to maintain direct bilirubin within a tight normal range of normal population

Protein C, protein S, antithrombin lll and factor V leiden [Q506] mutation in veno-occlusive disease in Egyptian children

Thickening of the subintimai zone of the central vein and sublobular venules leads to decreased venous outflow, increased resistance and severe hemodynamic changes characteristic of veno-occlusive disease [VOD]. The role of the coagulation pathways in the pathophysiology of VOD is an area of controversy. This work aimed at evaluation of the presence of protein C, protein S, antithrombin III deficiency and the presence of factor V Leiden in children having VOD. This cross-sectional study included 20 children suffering from veno-occlusive disease and 20 age and sex matched clinically free infants as a control group. They underwent protein C, protein S, antithrombin III assays. Molecular study of factor V mutation [mutation Q506] detection was carried out. The results proved that protein C deficiency was present in 14 children [70%], and antithrombin III in 2 children [10%]. Protein 8 deficiency was not encountered in our studied group. Two children were heterozygous for the mutation Q506. The 2 children with heterozygous factor V Leiden mutation had protein C deficiency. The percutaneous liver biopsies revealed central vein obstruction in 11 children [55%], extensive fibrosis in one and cirrhosis in one. The biopsy findings did not correlate with the clinical stage [P=0.47] or duration of disease [P=0.49]. None of these changes was encountered in the control group

Conclusion: We report the presence of protein C and antithrombin III deficiency and heterozygous Factor V Leiden [Q506] mutation in children with VOD. We support that thrombophilia is a host susceptibility factor and not the etiology of VOD