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Genetic and Epigenetic Associations of NAFLD: Focus on Clinical Decision Making

  • Fatty Liver Disease (S Harrison and J George, Section Editors)
  • Published:
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Abstract

Non-alcoholic fatty liver disease (NAFLD) afflicts more than one third of the population in affluent societies, paralleling the dramatic escalation in global obesity prevalence. NAFLD is thus a leading cause for end-stage liver disease, cancer, and liver transplantation and an estimated 20 million patients worldwide will eventually die of their liver disease Rinella and Charlton (Hepatology 2016;64:19–22). Furthermore, NAFLD increases the risk of type 2 diabetes and cardiovascular disease. NAFLD comprises a complex disease phenotype ranging from simple steatosis, through to steatohepatitis, fibrosis, and ultimately, cirrhosis and hepatocellular carcinoma. NAFLD is also characterized by considerable inter-individual variability in disease spectrum and outcomes. Thus, NAFLD best resembles a complex disease trait resulting from the dynamic interaction of environmental factors (e.g., caloric intake and composition, energy expenditure, the microbiome) acting on a susceptible polygenic host background. Genome-wide association studies (GWAS) and candidate gene studies have enriched our understanding of genetic factors contributing to the known inter-individual variation in NAFLD phenotypes including hepatic steatosis, inflammation, and fibrosis. The role of other types of genetic variations and epigenetics are also now being unraveled. In this review, we summarize current knowledge about genetic and epigenetic associations of NAFLD and its potential clinical implications and future challenges in the field.

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Funding

Mohammed Eslam and Jacob George are supported by the Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney; a National Health and Medical Research Council of Australia (NHMRC) Program Grant (1053206) and Project grants (APP1107178 and APP1108422).

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  1. Storr Liver Centre, Westmead Institute for Medical Research, Department of Medicine, Westmead Hospital and University of Sydney, Sydney, NSW, 2145, Australia

    Mayada Metwally, Mohammed Eslam & Jacob George

  2. Department of Medicine, Westmead Hospital, Westmead, NSW, 2145, Australia

    Jacob George

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  1. Mayada Metwally
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  2. Mohammed Eslam
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  3. Jacob George
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The authors contributed equally to all aspects of this article.

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Correspondence to Jacob George.

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Mayada Metwally and Mohammed Eslam each declare no potential conflicts of interest.

Jacob George is a section editor for Current Hepatology Reports.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Fatty Liver Disease

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Metwally, M., Eslam, M. & George, J. Genetic and Epigenetic Associations of NAFLD: Focus on Clinical Decision Making. Curr Hepatology Rep 16, 335–345 (2017). https://doi.org/10.1007/s11901-017-0372-8

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