Extrahepatic complications of nonalcoholic fatty liver disease

Authors

  • Matthew J. Armstrong,

    Corresponding author
    1. NIHR Liver Biomedical Research Unit and Centre for Liver Research, University of Birmingham, Birmingham, UK
    • Address reprint requests to: Wing-Kin Syn, M.D., Liver Regeneration and Repair Group, 3rd Floor, Institute of Hepatology, Foundation for Liver Research, London WC1E 6HX, UK. E-mail: wsyn@doctors.org.uk or Matthew J. Armstrong, M.D., Wellcome Trust Clinical Research Fellow & Honorary Specialist Registrar in Hepatology, NIHR Liver Biomedical Research Unit and Centre for Liver Research, 5th Floor, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT. E-mail: mattyarm2010@googlemail.com.

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  • Leon A. Adams,

    1. School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
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  • Ali Canbay,

    1. Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Germany
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  • Wing-Kin Syn

    Corresponding author
    1. Regeneration and Repair, Institute of Hepatology, Foundation for Liver Research, London, UK
    2. Department of Hepatology, Barts Health NHS Trust, London, UK
    • Address reprint requests to: Wing-Kin Syn, M.D., Liver Regeneration and Repair Group, 3rd Floor, Institute of Hepatology, Foundation for Liver Research, London WC1E 6HX, UK. E-mail: wsyn@doctors.org.uk or Matthew J. Armstrong, M.D., Wellcome Trust Clinical Research Fellow & Honorary Specialist Registrar in Hepatology, NIHR Liver Biomedical Research Unit and Centre for Liver Research, 5th Floor, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, UK, B15 2TT. E-mail: mattyarm2010@googlemail.com.

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  • Potential conflict of interest: Nothing to report.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease, and is strongly associated with the metabolic syndrome. In the last decade, it has become apparent that the clinical burden of NAFLD is not restricted to liver-related morbidity or mortality, and the majority of deaths in NAFLD patients are related to cardiovascular disease (CVD) and cancer. These findings have fuelled concerns that NAFLD may be a new, and added risk factor for extrahepatic diseases such as CVD, chronic kidney disease (CKD), colorectal cancer, endocrinopathies (including type 2 diabetes mellitus [T2DM] and thyroid dysfunction), and osteoporosis. In this review we critically appraise key studies on NAFLD-associated extrahepatic disease. There was marked heterogeneity between studies in study design (cross-sectional versus prospective; sample size; presence/absence of well-defined controls), population (ethnic diversity; community-based versus hospital-based cohorts), and method of NAFLD diagnosis (liver enzymes versus imaging versus biopsy). Taking this into account, the cumulative evidence to date suggests that individuals with NAFLD (specifically, nonalcoholic steatohepatitis) harbor an increased and independent risk of developing CVD, T2DM, CKD, and colorectal neoplasms. We propose future studies are necessary to better understand these risks, and suggest an example of a screening strategy. (Hepatology 2014;59:1174–1197)

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