Background:Accurate prediction scores for liver steatosis are demanded to enable clinicians to noninvasively screen for nonalcoholic fatty liver disease (NAFLD). Several prediction scores have been developed, however external validation is lacking.Objective:The aim was to determine the diagnostic accuracy of four existing prediction scores in severely obese children, to develop a new prediction score using novel biomarkers and to compare these results to the performance of ultrasonography.Design and Results:Liver steatosis was measured using proton magnetic resonance spectroscopy in 119 severely obese children (mean age 14.3 ± 2.1 years, BMI z‐score 3.35 ± 0.35). Prevalence of steatosis was 47%. The four existing predictions scores (“NAFLD liver fat score,” “fatty liver index,” “hepatic steatosis index,” and the pediatric prediction score) had only moderate diagnostic accuracy in this cohort (positive predictive value (PPV): 70, 61, 61, 69% and negative predictive value (NPV) 77, 69, 68, 75%, respectively). A new prediction score was built using anthropometry, routine biochemistry and novel biomarkers (leptin, adiponectin, TNF‐alpha, IL‐6, CK‐18, FGF‐21, and adiponutrin polymorphisms). The final model included ALT, HOMA, sex, and leptin. This equation (PPV 79% and NPV 80%) did not perform substantially better than the four other equations and did not outperform ultrasonography for excluding NAFLD (NPV 82%).Conclusion:The conclusion is in severely obese children and adolescents existing prediction scores and the tested novel biomarkers have insufficient diagnostic accuracy for diagnosing or excluding NAFLD.

Purpose:To evaluate the diagnostic accuracy of ultrasonography (US) for the assessment of hepatic steatosis in severely obese adolescents, with proton magnetic resonance (MR) spectroscopy as the reference standard, and to provide insight on the infl uence of prevalence on predictive values by calculating positive and negative posttest probabilities. Materials and Methods:This prospective study was institutional review board approved. All participants, and/or their legal representatives, gave written informed consent. Sensitivity, specifi city, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the overall presence of steatosis and for the presence of substantial (moderate to severe) steatosis. Positive and negative posttest probabilities were calculated and plotted against prevalence. Results:A total of 104 children (47 male, 57 female) were prospectively included. Conclusion:Positive US results in severely obese adolescents cannot be used to accurately predict the presence and severity of hepatic steatosis, and additional imaging is required. Negative US results exclude the presence of substantial steatosis with acceptable accuracy. Steatosis prevalence differs among specifi c populations, strongly infl uencing posttest probabilities.q RSNA, 2011 1

NGS-based gene panel analysis in patients with obesity led to a definitive diagnosis of a genetic obesity disorder in 3.9% of obese probands, and a possible diagnosis in an additional 5.4% of obese probands. The highest yield was achieved in a selected paediatric subgroup, establishing a definitive diagnosis in 12 out of 164 children with severe early onset obesity (7.3%). These findings give a realistic insight in the diagnostic yield of genetic testing for patients with obesity and could help these patients to receive (future) personalised treatment.

Lifestyle intervention for non-alcoholic fatty liver disease: prospective cohort study of its efficacy and factors related to improvement Koot, B.G.P.; van der Baan-Slootweg, O.H.; Tamminga-Smeulders, C.L.J.; Pels Rijcken, T.H.; Korevaar, J.C.; van Aalderen, W.M.; Jansen, P.L.M.; Benninga, M.A. Published in:Archives of disease in childhood : 10.1136/adc.2010.199760 Link to publication Citation for published version (APA): Koot, B. G. P., van der Baan-Slootweg, O. H., Tamminga-Smeulders, C. L. J., Pels Rijcken, T. H., Korevaar, J. C., van Aalderen, W. M., ... Benninga, M. A. (2011). Lifestyle intervention for non-alcoholic fatty liver disease: prospective cohort study of its efficacy and factors related to improvement. Archives of disease in childhood, 96(7), 669-674. https://doi.org/10.1136/adc.2010.199760 DOI General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. p<0.001) and serum p<0.002). In multivariate regression analysis, improvement in the degree of steatosis and decrease in ALT and AST were all signifi cantly related to improvement in insulin resistance. Improvement in insulin resistance only explained a small part of the observed changes in transaminases. Conclusions A lifestyle intervention of 6 months is moderately effective in improving NAFLD in severely obese children. Improvement in insulin resistance is the clinical parameter most strongly associated with improvement in NAFLD. Other factors related to the successful treatment of NAFLD need to be identifi ed so that these can be a focus for new lifestyle and drug interventions.

Our study confirms a high frequency of functional constipation in children with obesity, using the Rome III criteria. However, abnormal colonic motility, as measured by CTT, was delayed in only a minority of patients. No relation was found between constipation in these children and fiber or fat intake.