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      A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

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          Abstract

          Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention.

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          Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

          Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9×10−10) and with hepatic inflammation (P=3.7×10−4). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
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            Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

            New England Journal of Medicine, 362(18), 1675-1685
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              Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults.

              Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, and its worldwide prevalence continues to increase with the growing obesity epidemic. This study assesses the epidemiology of NAFLD in adults based on clinical literature published over the past 30 years. To review epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults based on clinical literature published over the past 30 years. An in-depth search of PubMed (1980-2010) was based on five search terms: 'non-alcoholic fatty liver disease' OR 'non-alcoholic steatohepatitis' OR 'fatty liver' OR 'steatosis' AND 'incidence' [MeSH Terms] OR 'prevalence' [MeSH Terms] OR 'natural history'. Studies of paediatric cohorts were excluded. Articles were categorised by topic and summarised, noting generalisations concerning their content. Four study categories included NAFLD incidence, prevalence, risk factors and natural history. Studies related to NAFLD prevalence and incidence indicate that the diagnosis is heterogeneous and relies on a variety of assessment tools, including liver biopsy, radiological tests such as ultrasonography, and blood testing such as liver enzymes. The prevalence of NAFLD is highest in populations with pre-existing metabolic conditions such as obesity and type II diabetes. Many studies investigating the natural history of NAFLD verify the progression from NASH to advanced fibrosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is the most common cause of elevated liver enzymes. Within the NAFLD spectrum, only NASH progresses to cirrhosis and hepatocellular carcinoma. With the growing epidemic of obesity, the prevalence and impact of NAFLD continues to increase, making NASH potentially the most common cause of advanced liver disease in coming decades. © 2011 Blackwell Publishing Ltd.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                15 June 2016
                June 2016
                : 17
                : 6
                : 947
                Affiliations
                [1 ]Faculty of Life Sciences and Medicine, King’s College London, Strand, London WC2R 2LS, UK; jonathan.temple@ 123456kcl.ac.uk
                [2 ]Institute for Liver and Digestive Health, University College London, Rowland Hill Street, London NW3 2PF, UK; jiawei.li.10@ 123456ucl.ac.uk (J.L.); v.nguyen@ 123456ucl.ac.uk (V.N.)
                [3 ]Department of Gastroenterology and Hepatology, Guy’s and St Thomas’ Hospital, NHS Foundation Trust, Westminster Bridge Rd., London SE1 7EH, UK
                Author notes
                [* ]Correspondence: paul.sanchez@ 123456ucl.ac.uk (P.C.); j.oben@ 123456ucl.ac.uk (J.A.O.); Tel.: +44-207-433-2875 (P.C. & J.A.O.)
                Article
                ijms-17-00947
                10.3390/ijms17060947
                4926480
                27314342
                d8161e4b-e85a-4f46-898a-a483223a2c98
                © 2016 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 17 May 2016
                : 07 June 2016
                Categories
                Review

                Molecular biology
                nafld,steatosis,obesity,children,adolescent
                Molecular biology
                nafld, steatosis, obesity, children, adolescent

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