Serum microRNA-486-5p expression in obese Egyptian children and its possible association with fatty liver.

AIMS: Several microRNAs (miRNAs) are involved in regulating the process of adipogenesis. White adipose tissue is a major source for these miRNAs. We aimed to evaluate the expression of miR-486-5p in children with obesity and its possible association with nonalcoholic fatty liver disease (NAFLD). METHOD: This case-control study included 100 obese and overweight children and 100 normal-weight children of matched age and sex. All children were subjected to anthropometric measurements and evaluation of miR-486-5p expression levels using the SYBR green-based real-time RT-PCR technique. RESULTS: Obese children showed significantly up-regulated miR-486-5p gene expression (p value < 0.001) when compared to control group. MiR-486-5p gene expression showed significant positive correlation with weight (r = 0.924), BMI (r = 0.497), waist circumference (r = 0.387), fat mass (r = 0.361), LDL(r = 0.351), TG (r = 0.867), TC (r = 0.875) and presence of fatty liver (r = 0.760). The best cutoff value of miR-486-5p gene expression in the prediction of obesity was 0.44 with AUC 0.736 that has a sensitivity 60% and specificity 90%, CONCLUSION: The serum level of the miR-486-5p gene is up-regulated in obese and overweight children and might be an independent predictor for obesity and fatty liver susceptibility.

Mac-2 binding protein glycan isomer as noninvasive tool to assess liver fibrosis in children with chronic liver disease.

AIM: This study is aimed to measure the value of serum Mac-2 binding protein glycan isomer (M2BPGI) in children with chronic liver diseases in comparison with liver biopsy and serum biomarkers. METHODS: Comparative cross-sectional study included 100 children with chronic liver diseases and 50 healthy age/sex-matched control group. All subjects were evaluated via medical history, clinical, radiological and laboratory examinations. Liver biopsy was performed for studied patients and serum M2BPGI level was measured by Enzyme Linked Immune Sorbent Assay (ELISA) in all studied subjects. RESULTS: Serum M2BPGI level increased more significantly in chronic liver disease patients (6.04 ± 2.72 ng/ml) than in healthy controls (1.12 ± 0.83 ng/ml) (P < 0.001). M2BPGI level was significantly elevated with progressive fibrosis (P < 0.001), and differed significantly between high and low Child-Pugh score, pediatric end-stage liver disease score and model for end-stage liver disease score score. Serum M2BPGI was correlated with serum biomarkers and degree of fibrosis in patients. CONCLUSION: M2BPGI could be used as one of noninvasive tools for detecting and staging of hepatic fibrosis in Egyptian children with chronic liver disease.

Diagnostic value of serum cytokeratin-18 in children with chronic liver disease.

AIM: This study aimed to assess the diagnostic value of serum cytokeratin-18 (CK-18) in children with chronic liver diseases (CLD) and correlate its serum level with liver histology and other liver biomarkers. METHODS: This study included two groups, the first group included children with CLD and the second group included healthy matched age and gender subjects as a control group, complete history and clinical examination, and serum CK-18 was measured using the sandwich enzyme-linked immunosorbent assay technique. RESULTS: Serum concentrations of CK-18 were significantly elevated in CLD patients with mean ± standard deviation (1070.63 ± 699.2 ng/mL) compared to healthy controls mean ± standard deviation (203.95 ± 83.57 ng/mL). CK-18 levels were associated with a change in hepatocyte and portal tract (P = 0.005) as it was elevated with cirrhosis and fibrosis stage (P = 0.02) as it was elevated with moderate and severe fibrosis than mild fibrosis, also it showed a gradual increase in accordance with child Pugh score. There was a positive correlation between CK-18 levels and Total IgG, paediatric end-stage liver disease score and model for end-stage liver disease scores, the best cutoff point of CK-18 was 624 ng/mL, with sensitivity 93.06%, specificity 62.5% and diagnostic accuracy 90.0% for detection of fibrosis. CONCLUSION: CK-18 could be used as a non-invasive diagnostic marker in children with CLD.

Diagnostic value of soluble programmed cell death protein-1 in type-1 autoimmune hepatitis in Egyptian children.

Programmed cell death protein-1 (PDCD1) is considered a key factor in immune regulation and is expressed mainly on activated T cells. The current study aimed to assess the clinical value of soluble PDCD1/PD1 as a marker for diagnosing type-1 autoimmune hepatitis in children. Sixty children with chronic hepatitis as patients' groups further divided into autoimmune hepatitis group and other chronic liver disease group and 20 healthy children as a control group were enrolled in this study. All children have been studied for clinical profile, biochemical, histological features and serum level of soluble programmed cell death protein-1 by ELISA. There was a significant increase regarding soluble PDCD1/PD1 in the autoimmune hepatitis group than the chronic liver disease group, with the lowest level in the control group. Soluble PDCD1/PD1 level increased with higher fibrosis stage and higher Child Pugh score, also higher in relapsed patients than patients with complete remission in AIH groups. There was a positive correlation between soluble PDCD1/PD1 and PT, IgG, fibrosis stage, HAI, ALT, AST, simplified and revised score system, PELD and MELD among the AIH group. The best cutoff value of PDCD1/PD1 in the prediction of autoimmune hepatitis was 1.73 ng/ml with AUC:0.895 that has a sensitivity of 80%, specificity of 78%. sPDCD1/PD1 level represents a possible promising biomarker of AIH patients who will represent an incomplete response for regular treatment. This finding can be considered as the first step to prove the pivotal role of soluble PDCD1/PD1 in the diagnosis of AIH.

Clinical Value of Serum Interleukin-33 Biomarker in Infants With Neonatal Cholestasis.

OBJECTIVES: The present study aimed to estimate the value of serum interleukin-33 (IL-33) levels in infants with cholestasis, correlate serum IL-33 levels with the clinicopathological profile of infants with cholestasis, and compare its level with that of healthy infants who served as control. METHODS: Sixty infants with cholestasis were enrolled in the present study and divided into biliary atresia (BA) group and non-BA group, in addition to 30 healthy infants as a control group. All infants were analyzed for their clinical and biochemical features, histopathological profile, and serum level of IL-33 by enzyme-linked immune sorbent assay. RESULTS: Serum level of IL-33 in BA group (median 48.0, interquartile range: 28.9-106.2) was significantly higher than that of the non-BA group (median 17.3, interquartile range: 13.7-18.8 pg/mL) and both were higher than that of the control group. There was a positive correlation between serum IL-33 and aspartate aminotransferase, alanine aminotransferase, bilirubin (total and direct) levels, and fibrosis stage among the BA group. Serum IL-33 at a cut-off value of 20.8 pg/mL can detect BA with a specificity of 95% and a sensitivity of 96.7%. CONCLUSION: The significantly higher production of IL-33 in patients with BA compared to non-BA suggests a potential role of IL-33 for initiation and progression of the disease process, also, IL-33 may have a diagnostic role in infants with BA.

Association of NKX2-5, GATA4, and TBX5 polymorphisms with congenital heart disease in Egyptian children.

BACKGROUND: Several genes encoding transcription factors are known to be the primary cause of congenital heart disease. NKX2-5 and GATA4 were the first congenital heart disease-causing genes identified by linkage analysis. This study designed to study the association of five single-nucleotide variants of NKX2-5, GATA4, and TBX5 genes with sporadic nonsyndromic cases of a congenital cardiac septal defect in Egyptian children. METHODS: Venous blood samples from 150 congenital heart disease children (including a ventricular septal defect, atrial septal defect, tetralogy of Fallot, and patent ductus arteriosus) and 90 apparently healthy of matched age and sex were studied by polymerase chain reaction followed by direct sequencing in order to study two single-nucleotide variants of NKX2-5 (rs2277923, rs28936670), two single-nucleotide variants of GATA4 (rs368418329, rs56166237) and one single-nucleotide variant TBX5 (rs6489957). The distribution of genotype and allele frequency in the congenital heart diseases (CHD) group and control group were analyzed. RESULTS: We found different genotype frequencies of the two variants of NKX2-5, as CT genotype of rs2277923 was present in 58% and 36% in cases and control respectively, and TT genotype present in 6% of the cases. Also regarding missense variant rs28936670, heterozygous AG presented in 82% of the cases. Also, we observed a five prime UTR variant rs368418329, GT (42% of the cases) and GG (46% of the cases) genotypes showed the most frequent presentation in cases. While regarding a synonymous variant rs56166237, GT and GG were the most presented in cases (41.4%, 56% respectively) in contrast to control group (20%, 1.7% respectively). Also, a synonymous variant in TBX5, the distribution of genotype frequency was significantly different between the CHD group and control group. CT genotype of TBX5 -rs6489957 was found in 12 ASD, 24 VSD, six PDA, three aortic coarctation and nine fallot that represent 42% of the cases. CONCLUSIONS: Significantly higher frequency of different allelle of five variants was observed in cases when compared to the control group, with significant risky effect for the development of septal defect. In addition to two polymorphisms of NKX2-5 (rs2277923, rs28936670) variant in the cardiac septal defect, two variants in GATA4 (rs368418329, rs56166237) and one variant in TBX5 (rs6489957) seem to have a role in the pathogenesis of congenital heart disease.