Does Autophagy have a Role in the Pathogenesis of Pediatric Hepatic Steatosis?

Hepatic steatosis has become the most common cause of chronic liver disease among children worldwide.  Lipophagy has been considered as a pathway affecting steatosis development and progression. OBJECTIVE: this study aimed to evaluate the immunohistochemical expression of Beclin1 and LC3A in pediatric hepatic tissues with steatosis and to correlate their expression with clinicopathological parameters. METHODS: this study included 81 Egyptian pediatric patients with hepatic steatosis and 21 pediatric cases without hepatic steatosis. All specimens were stained by Beclin1 and LC3A antibodies. According to final diagnosis obtained from Pediatric Hepatology department, patients were divided into two groups: chronic liver disease (CLD) group that included 45 cases and inborn error of metabolism (IEM) group that included 36 cases. RESULTS: higher beclin1 expression was significantly correlated with higher stages of fibrosis and distorted liver architecture in CLD group, (P=0.043) for both. The control group showed higher positivity, percentage, as well as the median values of the H score of LC3A expression than did the CLD group or the IEM group (P=0.055, 0.001, and 0.008, respectively). Higher positivity of LC3A was significantly associated with higher stages of fibrosis and distorted liver architecture in the studied IEM group (P=0.021) for both. CONCLUSIONS: Varying intensity grades of LC3A and Beclin 1 immunohistochemical expression demonstrate the variation of autophagy at different phases of pediatric hepatic steatosis and varied disease etiology.

Extra-hepatic portal vein thrombosis in children: Single center experience.

Aim of the study: We aimed to discuss our experience in management of children with extra-hepatic portal vein thrombosis (EHPVT). Material and methods: This retrospective cohort study included 62 children with EHPVT. All patients' records were reviewed. The patients' socio-demographic data, post-natal history, disease presentation and clinical examination were collected. Data from laboratory investigations - complete blood count, liver function tests, renal function tests, abdominal ultrasound/Doppler studies, upper endoscopic findings and treatment regimens - were collected whenever available. Results: Of the 62 patients, 62.9% were male and 37.1% were female. The mean age at disease presentation was 3.5 ±2.7 years. The main initial clinical presentation of the disease was hematemesis and/or melena (30 cases; 48.4%). History of umbilical catheterization (UVC) was present in 60% of cases. The thrombophilia profile was assessed in 17 patients, of whom 12 (70.6%) were found to have a coagulation disorder. Splenomegaly was present in 91.7% of the patients. Hematological abnormalities in the form of cytopenias were present in most cases. Ultrasound revealed the presence of collaterals in 76.2%. Upper endoscopy showed the presence of varices in 45 cases, all of which needed endoscopic intervention, while in 11 cases the varices were either low grade or absent and thus were subjected only to medical treatment with propranolol and 6 cases were lost to follow-up. Splenectomy was done in only one case and 2 cases underwent the Rex operation. Conclusions: Variceal bleeding is the most common clinical presentation of EHPVT in children. UVC is still the main etiological factor of EHPVT in our cohort especially with presence of thrombophilic disorder.

A New Perspective on the Quality of Life of Children with Glycogen Storage Diseases.

Purpose: This study aimed to assess the quality of life (QoL) of children with glycogen storage disease (GSD) and their parents and to determine the impact of myopathies. Methods: A prospective case-control study was conducted at the Cairo University Children's Hospital and National Liver Institute, Menoufia University. A promising new style of questionnaire called the Stark Quality of Life Questionnaire was used to assess the quality of life. Results: Fifty-two children diagnosed with GSD (cases) and 55 age- and sex-matched healthy children (controls) were included. A statistically significant difference was found between cases and controls regarding food intake; mental behavior parameters such as mood, energy, and social contact; and physical behavior parameters such as running and tying shoelaces. Children with myopathies had significantly lower QoL scores in most of the parameters. Conclusion: GSDs alter children and their parents' mental and physical abilities. Lower QoL scores were detected in children with both skeletal myopathy and cardiomyopathy, but the difference was not statistically significant when compared with the children without myopathies.

MicroRNA-499 rs3746444 polymorphism in Egyptian children with biliary atresia.

AIM OF THE STUDY: We aimed to evaluate the association of microRNA-499 rs3746444 polymorphism and biliary atresia (BA) risk and its correlation with clinic-pathologic features of BA. MATERIAL AND METHODS: This study was performed on 300 Egyptian children (100 BA cases, 100 cases with cholestatic liver diseases other than BA and 100 healthy controls). Routine laboratory investigations, clinical examination and abdominal ultrasound were done. All infants were genotyped for miR-499 single nucleotide polymorphisms (SNPs) (rs3746444 A>G) by real-time polymerase chain reaction (PCR) fluorescence detection on a Rotor Gene Real Time PCR System (QIAGEN, GmbH) using fluorescent labeled probes. RESULTS: The AG genotype was the most prevalent genotype of miR-499 rs3746444 among the studied groups. A significantly higher frequency of the rs3746444 G allele was found in the BA cases than the other groups (odds ratio = 1.62). This polymorphism was also correlated with the degree of fibrosis in BA cases (p < 0.05). The miR-499 rs3746444 polymorphism (GG genotype) was significantly associated with severe form of BA and bad prognosis after the Kasai operation (p < 0.05). miR-499 rs3746444 polymorphism had no effect on the clinic-pathological features or the liver function status in the non-BA group. CONCLUSIONS: There is an association between the miR-499 SNP genotypes and the occurrence of BA. The variant allele G is the predominant allele in the BA group and is associated with severe liver inflammation and bad prognosis after the Kasai operation.

Serum superoxide dismutase activity in acute and chronic paediatric liver diseases.

BACKGROUND AND STUDY AIMS: Measuring serum superoxide dismutase (SOD) levels in infants and children having acute or chronic liver disease of different aetiologies, and correlating these levels with disease aetiology in an attempt to clarify the role of SOD as an antioxidant in these diseases. PATIENTS AND METHODS: We prospectively enrolled 58 infants and children and divided them into four groups: Group I, 24 patients with surgical cholestasis; group II, 11 patients with medical cholestasis; group III, nine patients with autoimmune chronic hepatitis; and group IV, 14 patients with viral hepatitis. Forty healthy age- and sex-matched children served as controls. Serum SOD activity was measured in all patients and controls using spectrophotometry. RESULTS: The level of SOD showed a statistically significant increase in patients with medical cholestasis compared to healthy controls (p<0.0001). SOD activity of other groups showed no significant difference compared to controls. CONCLUSIONS: Significantly increased serum SOD in infants and children with medical cholestasis is probably consequent to its increase in liver tissue in response to the liberation of reactive oxygen species. This suggests that products of free radical reactions might be involved in the pathogenesis and/or progression of medical cholestasis, and that SOD might attempt to minimise the liver injury.