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      Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Cardiometabolic Risk Factors in Adolescence: A Cross-Sectional Study of 1874 General Population Adolescents

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          Abstract

          Context:

          The impact of adolescent nonalcoholic fatty liver disease (NAFLD) on health, independent of fat mass, is unclear.

          Objective:

          The objective of the study was to determine the independent (of total body fat) association of ultrasound scan (USS)-determined NAFLD with liver fibrosis, insulin resistance, and dyslipidemia among healthy adolescents.

          Design:

          This was a cross-sectional analysis in participants from a UK birth cohort.

          Participants:

          One thousand eight hundred seventy-four (1059 female) individuals of a mean age of 17.9 years participated in the study.

          Main Outcomes:

          USS assessed liver stiffness (shear velocity, an indicator of fibrosis) and volume, fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin.

          Results:

          The prevalence of NAFLD was 2.5% [95% confidence interval (CI) 1.8–3.3] and was the same in females and males. Dual-energy X-ray absorptiometry determined total body fat mass was strongly associated with USS NAFLD: odds ratio 3.15 (95% CI 2.44–4.07) per 1 SD (∼10 kg) fat mass. Those with NAFLD had larger liver volumes and greater shear velocity. They also had higher fasting glucose, insulin, triglycerides, low-density lipoprotein cholesterol, alanine amino transferase, aspartate amino transferase, γ-glutamyltransferase, and haptoglobin and lower high-density lipoprotein cholesterol. Most associations were independent of total body fat. For example, after adjustment for fat mass and other confounders, hepatic shear velocity [mean difference 22.8% (95% CI 15.6–30.5)], triglyceride levels [23.6% (95% CI 6.0–44.2)], and insulin [39.4% (95% CI 10.7–75.5)] were greater in those with NAFLD compared with those without NAFLD.

          Conclusion:

          In healthy European adolescents, 2.5% have USS-defined NAFLD. Even after accounting for total body fat, those with NAFLD have more adverse levels of liver fibrosis and cardiometabolic risk factors.

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          Most cited references14

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          Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study.

          Ultrasound is used to screen for hepatic steatosis, the most common liver disease in the United States. However, few studies have prospectively evaluated the accuracy of ultrasound to diagnose hepatic steatosis. Therefore, a double blinded prospective study was performed in consecutive patients undergoing liver biopsy to evaluate the accuracy of ultrasound to diagnose hepatic steatosis. Real time ultrasound was performed just prior to the biopsy by a single investigator masked to the clinical diagnosis. The liver biopsy was reviewed by a pathologist masked to the clinical indication or sonographic findings. Of 73 consecutive patients studied, macrovesicular steatosis of any severity on biopsy was found in 46 (63%) and micro vesicular fat found in 51 (69.9%). The overall impression of the sonographer for the presence of macrovesicular hepatic steatosis of any degree had a sensitivity of 60.9% and a specificity of 100%. The sensitivity increased to 100% and the specificity to 90% when there was > or =20% of fat. The zonular distribution of the fat did not alter the diagnostic accuracy of ultrasound. Ultrasound had a poor yield in the diagnosis of microvesicular fat with an overall sensitivity of 43% and a specificity of 73%. The combination of increased echogenicity and portal vein blurring on ultrasound had the greatest sensitivity in the diagnosis of hepatic steatosis. Real time ultrasound using a combination of sonographic findings has a high specificity but underestimates the prevalence of hepatic steatosis when there is<20% fat.
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            The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis

            Objective To meta-analyse the diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis. Methods From a comprehensive literature search in MEDLINE, EMBASE, CINAHL and Cochrane (up to November 2009), articles were selected that investigated the diagnostic performance imaging techniques for evaluating hepatic steatosis with histopathology as the reference standard. Cut-off values for the presence of steatosis on liver biopsy were subdivided into four groups: (1) >0, >2 and >5% steatosis; (2) >10, >15 and >20%; (3) >25, >30 and >33%; (4) >50, >60 and >66%. Per group, summary estimates for sensitivity and specificity were calculated. The natural-logarithm of the diagnostic odds ratio (lnDOR) was used as a single indicator of test performance. Results 46 articles were included. Mean sensitivity estimates for subgroups were 73.3–90.5% (US), 46.1–72.0% (CT), 82.0–97.4% (MRI) and 72.7–88.5% (1H-MRS). Mean specificity ranges were 69.6–85.2% (US), 88.1–94.6% (CT), 76.1–95.3% (MRI) and 92.0–95.7% (1H-MRS). Overall performance (lnDOR) of MRI and 1H-MRS was better than that for US and CT for all subgroups, with significant differences in groups 1 and 2. Conclusion MRI and 1H-MRS can be considered techniques of choice for accurate evaluation of hepatic steatosis. Electronic supplementary material The online version of this article (doi:10.1007/s00330-010-1905-5) contains supplementary material, which is available to authorized users.
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              Insulin resistance in children: consensus, perspective, and future directions.

              Emerging data indicate that insulin resistance is common among children and adolescents and is related to cardiometabolic risk, therefore requiring consideration early in life. However, there is still confusion on how to define insulin resistance, how to measure it, what its risk factors are, and whether there are effective strategies to prevent and treat it. A consensus conference was organized in order to clarify these points. The consensus was internationally supported by all the major scientific societies in pediatric endocrinology and 37 participants. An independent and systematic search of the literature was conducted to identify key articles relating to insulin resistance in children. The conference was divided into five themes and working groups: background and definition; methods of measurement and screening; risk factors and consequences; prevention; and treatment. Each group selected key issues, searched the literature, and developed a draft document. During a 3-d meeting, these papers were debated and finalized by each group before presenting them to the full forum for further discussion and agreement. Given the current childhood obesity epidemic, insulin resistance in children is an important issue confronting health care professionals. There are no clear criteria to define insulin resistance in children, and surrogate markers such as fasting insulin are poor measures of insulin sensitivity. Based on current screening criteria and methodology, there is no justification for screening children for insulin resistance. Lifestyle interventions including diet and exercise can improve insulin sensitivity, whereas drugs should be implemented only in selected cases.
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                Author and article information

                Journal
                J Clin Endocrinol Metab
                J. Clin. Endocrinol. Metab
                jcem
                jceme
                jcem
                The Journal of Clinical Endocrinology and Metabolism
                Endocrine Society (Chevy Chase, MD )
                0021-972X
                1945-7197
                March 2014
                28 January 2014
                28 January 2014
                : 99
                : 3
                : E410-E417
                Affiliations
                Medical Research Council Integrative Epidemiology Unit (D.A.L., C.M.-W., E.A., A.F., L.D.H.) and School of Social and Community Medicine (D.A.L., C.M.-W., E.A., A.F., L.D.H.), University of Bristol, Bristol BS8 2BN, United Kingdom; University Hospitals Bristol National Health Service Foundation Trust (M.C.), Bristol BS1 3NU, United Kingdom; Institute of Cellular Medicine (C.D.), Faculty of Medical Sciences, Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom; and Institute of Cardiovascular and Medical Sciences (N.S.), BHF Glasgow Cardiovascular Research Centre, Faculty of Medicine, University of Glasgow, Glasgow G12 8TA, United Kingdom
                Author notes
                Address all correspondence and requests for reprints to: Professor Debbie A. Lawlor, Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom. E-mail: d.a.lawlor@ 123456bristol.ac.uk .
                Article
                13-3612
                10.1210/jc.2013-3612
                3955251
                24471572
                7528a9d6-e5ad-4ff3-b3ed-db3885a04837
                Copyright © 2014 by The Endocrine Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 September 2013
                : 19 December 2013
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                Hot Topics in Translational Endocrinology
                Endocrine Research

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