Nonalcoholic Fatty Liver Disease and Carotid Atherosclerosis in Children Lucia Pacifico, Vito Cantisani, Paolo Ricci, John...
Background <ul><li>Nonalcoholic fatty liver disease (NAFLD) is closely associated with several features of the metabolic s...
<ul><li>Although an association between hepatic steatosis and atherosclerotic risk factors has been described in adult pat...
SUBJECTS <ul><li>Period: 12-month </li></ul>CASES: Children with primary obesity CONTROLS: Healthy children   <ul><li>INCL...
MATERIALS AND METHODS <ul><li>All patients underwent: </li></ul><ul><li>a complete physical examination (including weight,...
MATERIALS AND METHODS <ul><li>liver ultrasound scanning  </li></ul><ul><li>- The severity of hepatic steatosis was graded ...
RESULTS   Values are means (95% confidence intervals) <0.0001 <0.0001 <0.0001 <0.0001 0.16 0.50 0.89 P 69 ( 68-70) 73 (72-...
RESULTS   Values are geometric means (95% confidence intervals) <0.01 17 (15-19) 35 (28-42) ALT <0.0001 <0.0001 <0.01 <0.0...
RESULTS Obese children 46,7% Values are means (95% confidence intervals) The diagnosis of NAFLD was based on ultrasoun sca...
RESULTS Obese children 46,7% Values are geometric means (95% confidence intervals) <0.01 <0.01 <0.05 0.43 <0.05 <0.05 0.31...
RESULTS   Variables independently associated with carotid IMT in obese children:  *  Results of a stepwise linear regressi...
CONCLUSIONS <ul><li>Our study indicate, for the first time, that:   </li></ul><ul><li>obese patients with NAFLD have a mar...
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Nonalcoholic fatty liver disease and carotid atherosclerosis in children

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Lucia Pacifico, Vito Cantisani, Paolo Ricci, John F. Osborn, Elisa Schiavo, Caterina Anania, Eva Ferrara, Giuliano Dvisic, and Claudio Chiesa

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Nonalcoholic fatty liver disease and carotid atherosclerosis in children

  1. 1. Nonalcoholic Fatty Liver Disease and Carotid Atherosclerosis in Children Lucia Pacifico, Vito Cantisani, Paolo Ricci, John F. Osborn, Elisa Schiavo, Caterina Anania, Eva Ferrara, Giuliano Dvisic, and Claudio Chiesa Departments of Pediatrics, Radiology, and Public Health Sciences, La Sapienza University of Rome; National Research Council, Rome, Italy Pacifico L, et al. Pediatr Res 2008; vol. 63, April issue. Epud ahead of print January 24, 2008
  2. 2. Background <ul><li>Nonalcoholic fatty liver disease (NAFLD) is closely associated with several features of the metabolic syndrome, a highly atherogenic condition. </li></ul>Its presence could signify a substantial cardiovascular risk above and beyond that conferred by individual risk factors 
  3. 3. <ul><li>Although an association between hepatic steatosis and atherosclerotic risk factors has been described in adult patients, possible relationships between NAFLD and atherosclerosis in children remain to be investigated </li></ul>OBJECTIVE  The aims of our study were to determine the presence of subclinical atherosclerosis (measured as carotid intima-media thickness,IMT) in obese children with and without NAFLD, and to evaluate correlates of carotid IMT
  4. 4. SUBJECTS <ul><li>Period: 12-month </li></ul>CASES: Children with primary obesity CONTROLS: Healthy children <ul><li>INCLUSION CRITERIA •BMI > 95th percentile for age and sex • evaluation for fatty liver upon detection of hepatomegaly and/or elevated liver chemistry </li></ul><ul><li>EXCLUSION CRITERIA </li></ul><ul><li>causes of chronic hepatitis other than obesity (ex. hepatitis B, C, Wilson’s disease, α -1-antitrypsin deficiency) </li></ul><ul><li>alcohol intake or smoking (where appropriate) </li></ul><ul><li>type 1 or 2 diabetes </li></ul><ul><li>any condition known to influence body composition </li></ul><ul><li>INCLUSION CRITERIA </li></ul><ul><li>BMI appropriate for age and sex </li></ul><ul><li>EXCLUSION CRITERIA </li></ul><ul><li>no history of alcohol consumption or smoking (where appropriate) </li></ul><ul><li>normal aminotransferase levels </li></ul><ul><li>normal liver ultrasound </li></ul><ul><li>negative serology for hepatitis B and C </li></ul>
  5. 5. MATERIALS AND METHODS <ul><li>All patients underwent: </li></ul><ul><li>a complete physical examination (including weight, height, BMI and determination of the stage of puberty). The degree of obesity (SD score) was quantified by Cole’s least mean square method. </li></ul><ul><li>measurements of systolic blood pressure (BP) and diastolic BP </li></ul><ul><li>laboratory tests including glucose, insulin, aminotransferases, total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, leptin and adiponectin </li></ul><ul><li>measurements of body composition </li></ul>
  6. 6. MATERIALS AND METHODS <ul><li>liver ultrasound scanning </li></ul><ul><li>- The severity of hepatic steatosis was graded as mild, moderate, or severe </li></ul><ul><li>carotid ultrasound </li></ul><ul><li>- The measurement was performed at the common carotid artery near the bifurcation during end diastole. We measured 4 values on each side, and maximum and mean IMT were calculated separately for each side </li></ul>
  7. 7. RESULTS Values are means (95% confidence intervals) <0.0001 <0.0001 <0.0001 <0.0001 0.16 0.50 0.89 P 69 ( 68-70) 73 (72-74) Diastolic BP mmHg 106 (104-108) 115 (109-120) Systolic BP mmHg -0.04 (-0.39-0.29) 1.92 (1.78-2.07) SD score-BMI 17.5 (16.6-18.4) 24.7 (23.8-25.7) BMI- kg/m 2 10 (33.3) 17 (27.4) Prepubertal stage: 14 (46.6) 34 (54.8) Gender – Male (%) 10.1 (8.8-11.3) 10.0 (9.4-10.7) Age - years Controls Obese children
  8. 8. RESULTS Values are geometric means (95% confidence intervals) <0.01 17 (15-19) 35 (28-42) ALT <0.0001 <0.0001 <0.01 <0.01 <0.0001 0.51 <0.05 0.67 <0.01 P 75 (65-87) 105 (90-123) Triglycerides mg/dL 144 (131-157) 146 (123-162) Total cholesterol mg/dL 0.39 (0.35-0.43) 0.49 (0.46-0.52) Mean IMT mm 0.40 (0.36-0.43) 0.53 (0.50-0.56) Maximum IMT mm 1.8 (1.5-2.1) 3 (2.4-3.7) HOMA-IR 8.2 (7.0-9.6) 13.7 (11.2-16.7) Insulin μ U/mL 6 (4.8-7.5) 17 (14.6-20) Leptin ng/dL 12.2 (10.0-14.9) 11 (9.6-12.8) Adiponectin ng/mL 42 (40-45) 38 (36-40) HDL mg/dL Controls Obese children
  9. 9. RESULTS Obese children 46,7% Values are means (95% confidence intervals) The diagnosis of NAFLD was based on ultrasoun scan 0.09 <0.01 0.81 0.24 0.90 0.56 0.59 P 110 (108-113) 115 (112-118) Systolic BP mmHg 72 (71-74) 74 (72-76) Diastolic BP mmHg 10 (9.0-11.0)) 10.4 (9.5-11.4) Age - years 19 (57.5) 15 (51.7) Gender – Male (%) 10 (30.3) 7 (24.1) Prepubertal stage 24.3 (23.0-25.6) 25.4 (24.2-26.5) BMI- kg/m 2 1.91 (1.67-2.15) 1.95 (1.82-2.07) SD score-BMI no NAFLD NAFLD
  10. 10. RESULTS Obese children 46,7% Values are geometric means (95% confidence intervals) <0.01 <0.01 <0.05 0.43 <0.05 <0.05 0.31 0.28 0.48 <0.0001 P 22 (18-27) 52 (39-65) ALT 99 (75-130) 108 (91-134) Triglycerides mg/dL 125 (93-167) 152 (132–174) Total cholesterol mg/dL 39 (37-42) 37 (34-40) HDL mg/dL 0.45 (0.42–0.48) 0.54 (0.50–0.58) Mean IMT m. 0.49 (0.46-0.52) 0.58 (0.54–0.62) Maximum IMT m. 12.7 (10.6–15.1) 9.3 (7.4–11.7) Adiponectin ng/mL 16.1 (12.9–20.2) 18.3 (14.4–23.4) Leptin ng/mL 2.5 (1.9–3.3) 4 (2.8–5.5) HOMA-IR 11 (8.8–14.7) 17.3 (12.6-23.7) Insulin μ U/mL no NAFLD NAFLD
  11. 11. RESULTS Variables independently associated with carotid IMT in obese children: * Results of a stepwise linear regression analysis started with the following independent variables: age, gender, pubertal stage, BMI, fat mass, systolic and diastolic BP, total and HDL cholesterol, triglycerides, HOMA-IR values, adiponectin and leptin levels. <0.01 <0.0001 P 1.022-1.084 1.041-1.119 95% CI for e b e b Coefficient, b Independent variable 1.083 0.080 Fatty liver severity score 1.053 0.053 Tanner stage Stepwise regression analysis*
  12. 12. CONCLUSIONS <ul><li>Our study indicate, for the first time, that: </li></ul><ul><li>obese patients with NAFLD have a marked increase in carotid IMT in comparison with control healthy children ; </li></ul><ul><li>carotid IMT is higher for obese children with NAFLD than obese children without liver involvement but with similar BMI; </li></ul><ul><li>3) the presence of NAFLD independently predicts carotid IMT after adjustment for a broad spectrum of potential confounders, including insulin resistance, a major atherogenic risk factor that is strongly correlated to NAFLD. </li></ul>

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