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      Comparison of diagnostic accuracy of screening tests ALT and ultrasound for pediatric non-alcoholic fatty liver disease

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          Abstract

          Alanine aminotransferase (ALT) and ultrasound (US) are the most commonly used tools for detecting non-alcoholic fatty liver disease (NAFLD). No direct comparison of these two modalities in children exists. We aimed to compare head-to-head the diagnostic accuracy of ALT and US and their combination for detecting NAFLD in children with obesity. Ninety-nine children with severe obesity underwent simultaneous serum-ALT and abdominal ultrasound (US steatosis score 0–3). Proton magnetic resonance spectroscopy was used as reference standard for detecting steatosis/NAFLD. ROC curve analyses were performed to determine diagnostic performance and to determine optimum screening cut-points aiming for a specificity ≥ 80%. The area under the ROC (AUROC) of ALT and US were not significantly different (0.74 and 0.70, respectively). At the optimal ALT threshold (≥40 IU/L), sensitivity was 44% and specificity was 89%. At the optimal US steatosis score (≥ 2), sensitivity was 51% and specificity was 80%. Combining ALT and US did not result in better accuracy than ALT or US alone.

          Conclusion: ALT and US have comparable and only moderate diagnostic accuracy for detecting hepatic steatosis in children with obesity. A stepwise screening strategy combining both methods does not improve diagnostic accuracy.

          What is Known:

          Alanine aminotransferase ( ALT) and ultrasound ( US) are the most commonly used tools for detecting non-alcoholic fatty liver disease ( NAFLD) .

          • ALT and ultrasound have mediocre accuracy in detecting steatosis in children with obesity.
          What is New:

          • In a head-to-head comparison, the difference in diagnostic accuracy of ALT and ultrasound in detecting steatosis is not significant.

          • A stepwise screening strategy combining both methods does not improve diagnostic accuracy .

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          Most cited references16

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          Body index measurements in 1996-7 compared with 1980.

          To compare the distribution of body mass index (BMI) in a national representative study in The Netherlands in 1996-7 with that from a study in 1980. Cross sectional data on height, weight, and demographics of 14 500 boys and girls of Dutch origin, aged 0-21 years, were collected from 1996 to 1997. BMI references were derived using the LMS method. The 90th, 50th, and 10th BMI centiles of the 1980 study were used as baseline. Association of demographic variables with BMI-SDS was assessed by ANOVA. BMI age reference charts were constructed. From 3 years of age onwards 14-22% of the children exceeded the 90th centile of 1980, 52-60% the 50th centile, and 92-95% the 10th centile. BMI was related to region, educational level of parents (negatively) and family size (negatively). The -0.9, +1.1, and +2.3 SD lines in 1996-7 corresponded to the adult cut off points of 20, 25, and 30 kg/m(2) recommended by the World Health Organisation/European childhood obesity group. BMI age references have increased in the past 17 years. Therefore, strategies to prevent obesity in childhood should be a priority in child public health.
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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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              Ultrasound scanning in the detection of hepatic fibrosis and steatosis.

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                Author and article information

                Contributors
                +31-205662906 , l.g.draijer@amc.uva.nl
                s.feddouli@hotmail.com
                a.e.bohte@amc.uva.nl
                baan0337@planet.nl
                tammopr@gmail.com
                m.a.benninga@amc.uva.nl
                j.stoker@amc.uva.nl
                b.g.koot@amc.uva.nl
                Journal
                Eur J Pediatr
                Eur. J. Pediatr
                European Journal of Pediatrics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-6199
                1432-1076
                22 March 2019
                22 March 2019
                2019
                : 178
                : 6
                : 863-870
                Affiliations
                [1 ]ISNI 0000000084992262, GRID grid.7177.6, Department of Pediatric Gastroenterology and Nutrition, , Amsterdam University Medical Centers, Location Academic Medical Center/Emma Children’s Hospital, ; Meibergdreef 9, 1100 AZ Amsterdam, The Netherlands
                [2 ]ISNI 0000000404654431, GRID grid.5650.6, Department of Radiology and Nuclear Medicine, , Amsterdam University Medical Centers, Location Academic Medical Center, ; Amsterdam, The Netherlands
                [3 ]Obesity Clinic Heideheuvel, Soestdijkerstraatweg 129, 1213 VX Hilversum, The Netherlands
                [4 ]Department of Radiology, Tergooi Hospital, Van Riebeeckweg 212, 1213 XZ Hilversum, The Netherlands
                Author notes

                Communicated by Peter de Winter

                Author information
                http://orcid.org/0000-0002-1840-1692
                Article
                3362
                10.1007/s00431-019-03362-3
                6511345
                30903305
                135b9b13-077a-46bf-a840-ecb02c69cb89
                © The Author(s) 2019

                Open Access This 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.

                History
                : 12 January 2019
                : 3 March 2019
                : 4 March 2019
                Funding
                Funded by: Amsterdam UMC (University of Amsterdam)
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2019

                Pediatrics
                nafld,children,obesity,screening,alt,ultrasound
                Pediatrics
                nafld, children, obesity, screening, alt, ultrasound

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