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      A clinically relevant method to screen for hepatic steatosis in overweight adolescents: a cross sectional study

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          Abstract

          Background

          To develop a screening algorithm to detect hepatic steatosis in overweight and obese adolescents.

          Methods

          We performed a cross sectional study of 129 overweight adolescents 13–18 yrs. The primary outcome, hepatic steatosis was defined as an intracellular triglyceride content > 5.5 mg/g and quantified using 1H-magenetic resonance spectroscopy. Primary predictor variables included, alanine and aspartate transaminases (ALT/AST) and features of the metabolic syndrome.

          Results

          Hepatic steatosis was present in 33 % of overweight and obese adolescents. Adolescents with hepatic steatosis were more likely to be boys (adjusted OR: 4.8; 95 % CI: 2.5–10.5), display a higher waist circumference (111 ± 12 vs 100 ± 13 cm, p < 0.001) and have metabolic syndrome (adjusted OR: 5.1; 95 % CI: 1.6–16.4). Serum ALT predicted hepatic steatosis in boys (AUC: 0.82; 95 % CI: 0.70–0.95; p < 0.001) but not girls (AUC = 0.63; 95 % CI: 0.46–0.75, p = 0.16). An ALT >20 U/L, combined with the presence of metabolic syndrome, male gender and an elevated waist circumference provided the best model (AUC 0.85) with high sensitivity (72 %) and specificity (82 %) and positive and negative predictive values of 61 % and 89 % respectively.

          Conclusions

          Serum transaminases provide modest predictive value for hepatic steatosis in youth. The ALT threshold for predicting hepatic steatosis is significantly lower than current clinical thresholds for predicting non-alcoholic fatty liver disease. The addition of ALT, presence of the metabolic syndrome and male gender significant improve the ability to predict hepatic steatosis.

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          Most cited references20

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          SAFETY study: alanine aminotransferase cutoff values are set too high for reliable detection of pediatric chronic liver disease.

          The appropriate alanine aminotransferase (ALT) threshold value to use for diagnosis of chronic liver disease in children is unknown. We sought to develop gender-specific, biology-based, pediatric ALT thresholds. The Screening ALT for Elevation in Today's Youth (SAFETY) study collected observational data from acute care children's hospitals, the National Health and Nutrition Examination Survey (NHANES, 1999-2006), overweight children with and without non-alcoholic fatty liver disease (NAFLD), and children with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. The study compared the sensitivity and specificity of ALT thresholds currently used by children's hospitals vs study-derived, gender-specific, biology-based, ALT thresholds for detecting children with NAFLD, HCV, or HBV. The median upper limit of ALT at children's hospitals was 53 U/L (range, 30-90 U/L). The 95th percentile levels for ALT in healthy weight, metabolically normal, liver disease-free, NHANES pediatric participants were 25.8 U/L (boys) and 22.1 U/L (girls). The concordance statistics of these NHANES-derived thresholds for liver disease detection were 0.85 (95% confidence interval [CI]: 0.74-0.96) in boys and 0.91 (95% CI: 0.83-0.99) in girls for NAFLD, 0.80 (95% CI: 0.70-0.91) in boys and 0.79 (95% CI: 0.69-0.89) in girls for HBV, and 0.86 (95% CI: 0.77-0.95) in boys and 0.84 (95% CI: 0.75-0.93) in girls for HCV. Using current children's hospitals ALT thresholds, the median sensitivity for detection of NAFLD, HBV, and HCV ranged from 32% to 48%; median specificity was 92% (boys) and 96% (girls). Using NHANES-derived thresholds, the sensitivities were 72% (boys) and 82% (girls); specificities were 79% (boys) and 85% (girls). The upper limit of ALT used in children's hospitals varies widely and is set too high to reliably detect chronic liver disease. Biology-based thresholds provide higher sensitivity and only slightly less specificity. Clinical guidelines for use of screening ALT and exclusion criteria for clinical trials should be modified. 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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            Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease.

            Nonalcoholic fatty liver disease (NAFLD), the most common cause of liver disease in children, is associated with obesity and insulin resistance. However, the relationship between NAFLD and cardiovascular risk factors in children is not fully understood. The objective of this study was to determine the association between NAFLD and the presence of metabolic syndrome in overweight and obese children. This case-control study of 150 overweight children with biopsy-proven NAFLD and 150 overweight children without NAFLD compared rates of metabolic syndrome using Adult Treatment Panel III criteria. Cases and controls were well matched in age, sex, and severity of obesity. Children with NAFLD had significantly higher fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure than overweight and obese children without NAFLD. Subjects with NAFLD also had significantly lower high-density lipoprotein cholesterol than controls. After adjustment for age, sex, race, ethnicity, body mass index, and hyperinsulinemia, children with metabolic syndrome had 5.0 (95% confidence interval, 2.6 to 9.7) times the odds of having NAFLD as overweight and obese children without metabolic syndrome. NAFLD in overweight and obese children is strongly associated with multiple cardiovascular risk factors. The identification of NAFLD in a child should prompt global counseling to address nutrition, physical activity, and avoidance of smoking to prevent the development of cardiovascular disease and type 2 diabetes.
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              Development of age-specific adolescent metabolic syndrome criteria that are linked to the Adult Treatment Panel III and International Diabetes Federation criteria.

              The study objectives were to develop age-specific adolescent metabolic syndrome (MetS) criteria that were linked to the health-based Adult Treatment Panel III (ATP) and International Diabetes Federation (IDF) adult criteria. There has been no consistency in the criteria used to diagnose the MetS in adolescents. Studies have either applied adult criteria or arbitrarily chosen adolescent high-risk cut-points. The adolescent (12 to 19 years old) MetS criteria developed in this study were linked to the ATP and IDF adult criteria with LMS growth curve modeling for each MetS component (waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, and glucose). Nationally representative data from the National Health and Nutrition Examination Surveys were used to develop the growth curves. The growth curves for each MetS component passed through the ATP and IDF cut-points at 20 years of age such that adolescent cut-points were linked to the adult values. Age- and gender-specific cut-points for each MetS component were developed that can be used to define high-risk values in 12- to 19-year-olds. The prevalence of MetS in adolescents nearly doubled over the last decade and was 7.6% on the basis of the newly developed ATP adolescent criteria and 9.6% on the basis of the newly developed IDF adolescent criteria. These new criteria should provide improved and age-appropriate approaches for diagnosing MetS among adolescents.
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                Author and article information

                Contributors
                vsaad@hsc.mb.ca
                bwicklow@hsc.mb.ca
                kwittmeier@hsc.mb.ca
                jhay@chrim.ca
                amacintosh@chrim.ca
                niranjan.venugopal@gmail.com
                lryner@cancercare.mb.ca
                lberard@hsc.mb.ca
                1-204-480-1359 , jmcgavock@chrim.ca
                Journal
                BMC Pediatr
                BMC Pediatr
                BMC Pediatrics
                BioMed Central (London )
                1471-2431
                8 October 2015
                8 October 2015
                2015
                : 15
                : 151
                Affiliations
                [ ]Children’s Hospital Research Institute of Manitoba, 511 JBRC. 715 McDermot Avenue, Winnipeg, Mb R3E 3P4 Canada
                [ ]Department of Pediatrics and Child Health, Faculty of Health Sciences, College of Medicine University of Manitoba, Manitoba Institute of Child Health, 511 JBRC. 715 McDermot Avenue, Winnipeg, MB R3E 3P4 Canada
                [ ]George and Fay Yee Centre for Healthcare Innovation, 300 Chown Building, 753 McDermot Avenue, Winnipeg, MB R3E 0T6 Canada
                [ ]CancerCare Manitoba, 675 McDermot Avenue, Winnipeg, MB R3E 0 V9 Canada
                [ ]The Diabetes Research Group, Department of Internal Medicine, Faculty of Medicine, University of Manitoba, 835 McDermot Avenue, Winnipeg, MB R3E 0 T8 Canada
                [ ]Diabetes Research Envisioned and Accomplished in Manitoba Theme, 715 McDermot Avenue, Winnipeg, Mb R3E 3P4 Canada
                Article
                465
                10.1186/s12887-015-0465-x
                4599758
                ec8bbc94-5c41-4644-8564-91c2751a840d
                © Saad et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 31 December 2014
                : 25 September 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                Pediatrics
                fatty liver,alt,magnetic resonance spectroscopy,adolescents,obesity,lipotoxicity
                Pediatrics
                fatty liver, alt, magnetic resonance spectroscopy, adolescents, obesity, lipotoxicity

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