Metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease.

OBJECTIVE: To examine the role of metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease. STUDY DESIGN: In 50 obese children (age 7 to 14 years) with (n = 20, group 1) or without (n = 30, group 2) hypertransaminasemia and ultrasonographic liver brightness, we studied insulin resistance (fasting glucose/insulin ratio [FGIR]) and serum levels of leptin, iron, transferrin, ferritin, C-reactive protein (CRP), white blood cell (WBC) count, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, C282Y and H63D mutations, and erythrocytic glutathione peroxidase (GPX) activity. RESULTS: FGIR (6.7 +/- 4.1 vs 9.2 +/- 5.2; P = .02), serum ferritin (88.8 +/- 36.0 vs 39.9 +/- 24.0 ng/mL; P = .0001), serum CRP (5.4 +/- 6.0 vs 1.1 +/- 1.6 mg/dL; P = 0.004), and GPX (8.4 +/- 0.9 vs 5.0 +/- 0.5 U/g Hb; P = .05) were significantly higher and more frequently deranged in group 1 than in group 2. FGIR, ferritin, and CRP values were simultaneously deranged in 41% of the group 1 patients and in none of the group 2 patients ( P = .098). Serum leptin, iron, and transferrin, WBC, TNF-alpha, IL-6, and C282Y and H63D mutations were similar in the 2 groups. CONCLUSIONS: Insulin resistance, oxidative stress, and low-grade systemic inflammatory status are implicated in pediatric obesity-related liver disease. These findings may be useful in planning pathophysiologically based therapeutic trials for hepatopathic obese children who are unable to follow hypocaloric diets.

Per-rectal portal scintigraphy is complementary to ultrasonography and endoscopy in the assessment of portal hypertension in children with chronic cholestasis.

UNLABELLED: We evaluated the clinical usefulness of 99mTc-pertechnetate per-rectal portal scintigraphy (PPS) in the assessment of portal circulation in children with chronic cholestasis. METHODS: PPS percentage shunt index (%SI) (the amount of radionuclide that shunts the liver and reaches the systemic blood after injection in the rectum) was measured in 22 children (mean age, 7.2 +/- 4.9 y) and compared with established clinical, laboratory, and endoscopic and imaging parameters of portal hypertension (PH). Fourteen children had surgically treated biliary atresia, and 8 had chronic intrahepatic cholestasis. Six clinically well children served as control subjects. RESULTS: The %SI was 14.3 +/- 3.1 and 34.7 +/- 18.8 in controls and in patients, respectively (P < 0.01). A cutoff of 19% correctly allocated 100% of controls and 86% of patients. Mean %SI values were significantly higher in patients with biliary atresia, a high risk of pretransplantation death, esophageal varices (EV) at endoscopy, and an abnormal value for the ratio of lesser omentum thickness to abdominal aorta diameter (LO/Ao) at ultrasonography. Correlations between %SI values and several ultrasonographic continuous variables were statistically significant only for LO/Ao ratios (r = 0.51; P = 0.005) and spleen longitudinal diameters (r = 0.53; P = 0.01). The presence of EV could correctly be predicted only when values of %SI were greater than 30% (100% specificity; 56% sensitivity). Endoscopic and PPS findings agreed for a diagnosis of PH with EV in 3 of 7 patients with normal or borderline ultrasonographic LO/Ao ratios. PPS patterns and %SI values became normal in 3 children who underwent liver transplantation. CONCLUSION: In children with chronic cholestasis, PPS may be an advantageous, minimally invasive tool complementary to ultrasonography and endoscopy for better assessment and follow-up of PH before and after liver transplantation.

Vitamin E treatment in pediatric obesity-related liver disease: a randomized study.

OBJECTIVE: A beneficial role of antioxidants in hepatopathic obese individuals has hitherto been inferred only from uncontrolled pilot studies. The authors compared the effect of vitamin E and weight loss on transaminase values and on ultrasonographic bright liver in a controlled group of children with obesity-related liver dysfunction. METHODS: Twenty-eight children with obesity-related hypertransaminasemia and bright liver were randomly allocated to two single-blind groups: group 1 (n = 14) treated with a low-calorie diet associated with oral placebo for 5 months, and group 2 (n = 14) treated with a low-calorie diet associated with oral vitamin E (400 mg/d x 2 months, 100 mg/d x 3 months). Transaminase values and ultrasonographic liver brightness along with weight loss and vitamin E levels were monitored. RESULTS: Variations in transaminase levels and percentage of patients with normalized transaminase values were comparable in the two groups. The disappearance of bright liver was observed only in patients who lost weight and was twice as common in patients from group 1. Two subgroups of patients with complete normalization of transaminase values emerged as a consequence of controlled adherence to diet alone (n = 6; significant decrease of percent overweight: P = 0.0019 ) and to vitamin E alone (n = 7; unmodified percent overweight and significant increase of vitamin E/cholesterol ratio: P < 0.0001). Changes in treatment-induced alanine aminotransferase levels in these two subgroups were comparable at month 2, whereas values at month 5 were significantly lower in the subgroup adherent to diet alone (P = 0.04). In the subgroup adherent to vitamin E alone, after 2 months washout, transaminase remained stable in 5 patients and increased in 2; bright liver persisted in all. CONCLUSIONS: Oral vitamin E warrants consideration in obesity-related liver dysfunction for children unable to adhere to low-calorie diets.