Assessment of plasma catecholamines in patients with dysmetabolic iron overload syndrome.

BACKGROUND: Dysmetabolic iron overload syndrome (DIOS) is characterized by hyperferritinemia and normal transferrin saturation level with components of metabolic syndrome (MS). Among cases of MS, we determined those with DIOS and their characterizations, then we evaluated the association between plasma catecholamines status and hypertension in DIOS. METHODS: We compared 101 hypertensive patients with 50 healthy participants (control group). Iron (iron, transferrin, and ferritin), insulin, and plasma catecholamine (adrenaline, noradrenaline, and dopamine), profiles were measured for both groups. Homeostasis model assessment of insulin resistance index and transferrin saturation were also calculated. RESULTS: Out of 101 hypertensive patients, 64 were diagnosed with MS, and 6 of the latter met the DIOS diagnostic criteria. Significantly, DIOS patients were older and had lower body mass index (BMI) compared with hypertensive non-DIOS patients with p-values of (0.026), and (0.033), respectively. Adrenaline, noradrenaline, and dopamine levels did not differ significantly between DIOS and non-DIOS patients. CONCLUSIONS: Of the MS patients, 9.3% were diagnosed with DIOS. Accordingly, complete iron profiling should be performed routinely in the cases of MS for early diagnosis of DIOS, to prevent future complications. Further studies are required to test the hypothesis linking older age and lower BMI with the pathogenesis of DIOS.

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.

Detection of an earlier tubulopathy in diabetic nephropathy among children with normoalbuminuria.

INTRODUCTION: Diabetic nephropathy is a major cause of morbidity and mortality among young adults with type 1 diabetes mellitus (DM). Albuminuria, the gold standard for early diagnosis, cannot always detect early diabetic nephropathy. We aimed at evaluating the level of urine neutrophil gelatinase-associated lipocalin (NGAL) as a marker of tubulointerstitial damage in children and adolescents with type 1 DM in relation to the level of albuminuria and other parameters. MATERIALS AND METHODS: Fifty children with type 1 DM for more than 5 years were included in this study (mean age, 13.8 ± 4.0 years), and 18 healthy children served as controls. Patients with overt albuminuria (> 300 mg/g creatinine) or inflammatory states were excluded. Urine NGAL, microalbuminuria, and urine albumin-creatinine ratio were measured in patients and controls as well as other parameters. RESULTS: Urine NGAL was significantly higher in microalbuminuric in comparison with normoalbuminuric patients and controls, and correlated positively with urine albumin-creatinine ratio. A positive urine NGAL was observed in 12 of 38 normoalbuminuric patients (31.6%) compared to 9 of 12 microalbuminuric patients (75%). A positive correlation was reported between urine NGAL and both Hemoglobin A1c and duration of DM, but not with estimated glomerular filtration rate or hypertension. CONCLUSIONS: Diabetic children, even some normoalbuminurics, showed increased urine NGAL. This finding may support the hypothesis of a "tubular phase" of diabetic disease preceding overt diabetic nephropathy, and hence, the use of urine NGAL measurement for early evaluation of renal involvement.

Reliability of risk-based screening for hepatitis C virus infection among pregnant women in Egypt.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) only recommends risk-based HCV screening for pregnant women in the United States. This study sought to determine the reliability of risk-based versus universal HCV screening for pregnant women in Egypt, a country with the world's highest HCV prevalence that also relies on risk-based screening, and to identify additional characteristics that could increase the reliability of risk-based screening. METHODS: Pregnant women attending the Cairo University antenatal clinic were tested for anti-HCV antibodies and RNA, and demographic characteristics and risk factors for infection were assessed. RESULTS: All 1250 pregnant women approached agreed to participate (100%) with a mean age of 27.4 ± 5.5 years (range:16-45). HCV antibodies and RNA were positive in 52 (4.2%) and 30 (2.4%) women respectively. After adjustment, only age (OR:1.08, 95%CI:1.002-1.16, p < 0.01), history of prior pregnancies (OR:1.20, 95%CI:1.01-1.43, p < 0.04), and working in the healthcare sector (OR:8.68, 95%CI:1.72-43.62, p < 0.01), remained significantly associated with chronic HCV infection. CONCLUSIONS: Universal antenatal HCV screening was widely accepted (100%) and traditional risk-based screening alone would have missed 3 (10%) chronically infected women, thereby supporting universal screening of pregnant women whenever possible. Otherwise, risk-based screening should be modified to include history of prior pregnancy and healthcare employment.

The value of different insulin resistance indices in assessment of non-alcoholic fatty liver disease in overweight/obese children.

OBJECTIVE: The aim of the present study was to determine the association between insulin resistance (IR) and both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in a group of Egyptian overweight/obese children and adolescents and to evaluate different IR indices in detection of NAFLD. PATIENTS AND METHODS: The study included 76 overweight/obese children aged 2-15 years; 52.6% were males. Laboratory analysis included fasting blood glucose, serum insulin, lipid profile, liver biochemical profile, and liver ultrasound. IR was calculated using the following indices; the homeostasis model assessment method (HOMA-IR), the quantitative insulin-sensitivity check index (QUICKI) and hepatic insulin sensitivity. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of MetS. Liver biopsy was done when medically indicated and accepted by parents. RESULTS: IR was detected in 43.4% and 34.2% by using QUICKI and HOMA, respectively. MetS was detected in 36.8% and NAFLD was detected in 45.5% among those performing liver biopsy. Cases with NAFLD had more frequent IR than children with normal histology. QUICKI showed significant difference between normal subjects and both steatosis and non-alcoholic steatohepatitis; while HOMA-IR was sensitive in cases with NASH only. MetS was present in 100% of patients with NASH and in 75% of those with steatosis and they were all obese. Patients with NASH had significantly higher ALT than those with normal histology. CONCLUSION: IR was significantly associated with NAFLD. QUICKI is considered more sensitive than HOMA-IR in differentiating simple steatosis from normal liver histology.

Gene mutations in Wilson disease in Egyptian children: report on two novel mutations.

BACKGROUND AND STUDY AIMS: Wilson disease (WD) is an autosomal recessive disorder, caused by defects in copper-transporting P-type adenosine triphosphatase (ATPase) encoded by the ATP7B gene, resulting in the deposition of copper in the liver and brain with significant disability or death if left untreated. An available regimen of treatment gives hope to those predisposed to the disease if diagnosed early. The objective of this study was to determine the frequency of the most common European mutation (p.H1069Q) in Egyptian children with WD, in addition to screening for previously reported mutations in the Egyptian patients in our selected group. PATIENTS AND METHODS: Direct DNA sequencing was applied to exons (13, 14, 18, and 19) of the ATP7B gene for 19 patients previously diagnosed with WD. Then DNA sequencing and pedigree analysis were performed in the families of the patients showing variations in their results for the purpose of family screening and carrier detection. Six out of 19 patients were studied with their families (three families). RESULTS: We identified five variants of which two were novel among the studied patients. One of the novel variants was synonymous substitution (p.A1074A) in 16% of patients and the other was predicted to be missense disease-causing mutations (p.T1076I) in 16% of patients, and three previously published mutations p.H1069Q were detected in 5% of patients, p.P1273Q in 10% of patients, and a silent variant p.A1003A in 26% of patients. CONCLUSION: Screening for the two exons 14 and 18 of the ATP7B gene is important in Egyptian patients especially in suspected patients without hepatic manifestations.

Glycogen storage disease type III in Egyptian children: a single centre clinico-laboratory study.

BACKGROUND AND STUDY AIMS: Glycogen storage disease type III (GSD III) is an autosomal recessive disorder caused by deficiency of glycogen debrancher enzyme and is characterised by clinical variability. PATIENTS AND METHODS: We herein describe the clinical and laboratory findings in 31 Egyptian patients with GSD III presenting to the Paediatric Hepatology Unit, Cairo University, Egypt. RESULTS: Eighteen patients (58%) were males. Their ages ranged between 6 months to 12 years. The main presenting complaint was progressive abdominal distention in 55%. Twelve patients (38.7%) had a history of recurrent attacks of convulsions; four had an erroneous diagnosis of hypocalcaemia and epilepsy. Doll-like facies was noted in 90%. Abdominal examination of all cases revealed abdominal distention and soft hepatomegaly which had bright echogenicity by ultrasound. Hypertriglyceridaemia was present in 93.6%, hyperlactacidaemia in 51.6% and hyperuricaemia in 19.4%. Liver biopsy showed markedly distended hepatocytes with well distinct cytoplasmic boundaries and 32% had macrovesicular fatty changes. Serum creatine kinase was elevated in 64.6% of patients and correlated positively and significantly with age (r=0.7 and P=<0.001), while serum triglycerides correlated negatively with age (r=-0.4 and P=0.05). CONCLUSION: Blood glucose assessment and search for hepatomegaly in an infant with recurrent seizures may prevent delay in the diagnosis. A huge soft liver reaching the left midclavicular line that appears echogenic on ultrasonography is characteristic of GSD III. A distended hepatocyte with rarified cytoplasm is pathognomonic but not diagnostic. Hypertriglyceridaemia correlates negatively with age, in contrary to CK level.

Aberrant p16INK4A methylation: Relation to viral related chronic liver disease and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is currently the fifth most common solid tumor worldwide and the third leading cause of cancer related deaths. Several studies have shown that the tumor suppressor gene p16INK4A is frequently downregulated by aberrant methylation of the 5'-cytosine-phosphoguanine island within the promoter region. AIM: To find out the frequency of methylated p16INK4A in the peripheral blood of HCC and cirrhotic patients and to evaluate its role in hepatocarcinogenesis. PATIENTS AND METHODS: This study was performed on 58 subjects: 30 HCC patients, 20 cirrhotic patients, and eight healthy volunteers. Methylation of p16INK4A was examined using methylation specific polymerase chain reaction (PCR) (MSP). Comparison of quantitative variables between the study groups was done using Mann-Whitney U test for independent samples when not normally distributed. For comparing categorical data, Chi-square (χ(2)) test was performed. Exact test was used instead when the expected frequency was less than 5. RESULTS: Methylation of p16INK4A was found in 6.7% of HCC patients, 5% of liver cirrhosis (LC) patients, and none of the healthy volunteers; 66.67% of the p16INK4A-methylated cases (2/3) were positive for anti-hepatitis C virus (HCV) antibodies (one of them had HCC). All HCC cases with aberrant p16INK4A methylation show very high serum alpha fetoprotein (AFP) level (9,080; 30,000 µg/mL). There were no significant associations between the status of p16INK4A methylation and tumor size. CONCLUSION: Hypermethylation of p16INK4A was found to be infrequent among Egyptian patients with HCC.

The association of metabolic syndrome, insulin resistance and non-alcoholic fatty liver disease in overweight/obese children.

BACKGROUND/AIM: To study the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in overweight/obese children with clinical hepatomegaly and/or raised alanine aminotransferase (ALT). PATIENTS AND METHODS: Thirty-three overweight and obese children, aged 2-13 years, presenting with hepatomegaly and/or raised ALT, were studied for the prevalence of MS, IR and NAFLD. Laboratory analysis included fasting blood glucose, serum insulin, serum triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and liver biochemical profile, in addition to liver ultrasound and liver biopsy. RESULTS: Twenty patients (60.6%) were labeled with MS. IR was present in 16 (48.4%). Fifteen (44%) patients had biopsy-proven NAFLD. Patients with MS were more likely to have NAFLD by biopsy (P=0.001). Children with NAFLD had significantly higher body mass index, waist circumference, ALT, total cholesterol, LDL-c, TG, fasting insulin, and lower HDL-c compared to patients with normal liver histology (P< 0.05) and fitted more with the criteria of MS (80% vs. 44%). IR was significantly more common among NAFLD patients (73% vs. 28%). CONCLUSION: There is a close association between obesity, MS, IR and NAFLD. Obese children with clinical or biochemical hepatic abnormalities are prone to suffer from MS, IR and NAFLD.

Predictors of non-alcoholic fatty liver disease in obese and overweight Egyptian children: single center study.

BACKGROUND/AIM: Pediatric non-alcoholic fatty liver disease (NAFLD) is a global problem which has been increasingly recognized with the dramatic rise in pediatric obesity. The aim of the present study was to identify the clinical, sonographic, and biochemical predictors for NAFLD in obese children. MATERIALS AND METHODS: Seventy-six children (2-15 years) were included after an informed consent. All were subjected to full anthropometric assessment (including height, weight, body mass index, subscapular skin fold thickness, waist and hip circumference and calculation of waist: hip ratio), biochemical assessment of liver function tests, lipid profile and insulin resistance and sonographic assessment of hepatic echogenicity. Liver biopsy when indicated, was done in 33 patients. RESULTS: Sixteen patients (21%) had elevated ALT and 6 (7.9%) had elevated AST. Significant dyslipidemia (low HDL-c, high total cholesterol, high LDL-c and triglycerides) and higher insulin resistance were found in obese patients (P<0.01). The main sonographic findings were hepatomegaly in 20 patients (26.3%) and echogenic liver in 41 patients (53.9%). Liver biopsy showed simple steatosis in eight cases (24.2%) and non-alcoholic steatohepatitis (NASH) in seven cases (21.2%). Anthropometric measurements, increased hepatic echogenicty by ultrasound, insulin resistance and lipid profile were good predictors of NAFLD in obese children if assessed together. However, LDL-c was the only sensitive predictor (independent variable) for NAFLD in both uni- and multivariate logistic regression analyses. CONCLUSION: Dyslipidemia per se is a strong predictor of NAFLD among obese Egyptian children.