title: Nonalcoholic fatty liver disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by excess accumulation of fat in hepatocytes (nonalcoholic fatty liver (NAFL)); in up to 40% of individuals, there are additional findings of portal and lobular inflammation and hepatocyte injury (which characterize nonalcoholic steatohepatitis (NASH)). A subset of patients will develop progressive fibrosis, which can progress to cirrhosis. Hepatocellular carcinoma and cardiovascular complications are life-threatening co-morbidities of both NAFL and NASH. NAFLD is closely associated with insulin resistance; obesity and metabolic syndrome are common underlying factors. As a consequence, the prevalence of NAFLD is estimated to be 10-40% in adults worldwide, and it is the most common liver disease in children and adolescents in developed countries. Mechanistic insights into fat accumulation, subsequent hepatocyte injury, the role of the immune system and fibrosis as well as the role of the gut microbiota are unfolding. Furthermore, genetic and epigenetic factors might explain the considerable interindividual variation in disease phenotype, severity and progression. To date, no effective medical interventions exist that completely reverse the disease other than lifestyle changes, dietary alterations and, possibly, bariatric surgery. However, several strategies that target pathophysiological processes such as an oversupply of fatty acids to the liver, cell injury and inflammation are currently under investigation. Diagnosis of NAFLD can be established by imaging, but detection of the lesions of NASH still depend on the gold-standard but invasive liver biopsy. Several non-invasive strategies are being evaluated to replace or complement biopsies, especially for follow-up monitoring.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 Euclid Avenue, Campus Box 8118, Saint Louis, Missouri 63110, USA.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Brunt
authors.affiliation: Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Vincent W-S
authors.initials: VW
authors.lastname: Wong
authors.affiliation: Hepatometabolic Unit, Bambino Gesu Children Hospital, Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Day
authors.affiliation: Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires, National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.affiliation: Department of Medicine, University of California at San Francisco, San Francisco, California 94110, USA.
authors.forename: Jacquelyn J
authors.initials: JJ
authors.lastname: Maher
authors.affiliation: Department of Medical Sciences, University of Torino, Città della Salute e della Scienza, Torino, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bugianesi
authors.affiliation: Liver Imaging Group, Department of Radiology, University of California at San Diego, San Diego, California 92103, USA.
authors.forename: Claude B
authors.initials: CB
authors.lastname: Sirlin
authors.affiliation: Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, Saint Louis, Missouri 63110, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Neuschwander-Tetri
authors.affiliation: Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Rinella
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology; D018450:Disease Progression; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000209:etiology; D008113:Liver Neoplasms / Q000209:etiology; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications / Q000473:pathology / Q000503:physiopathology