title: Biomarkers in nonalcoholic fatty liver disease.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers.
  
  
  OBJECTIVE
  To review the biomarkers used to diagnose and define the severity of NAFLD and NASH.
  
  
  METHODS
  A comprehensive PubMed and Google Scholar literature search was performed using the terms "non-alcoholic fatty liver disease", "non-alcoholic steatohepatitis", as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed.
  
  
  RESULTS
  Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity.
  
  
  CONCLUSIONS
  The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical considerations of each biomarker pointing out sentinel features of disease progression.
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Neuman
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Cohen
authors.forename: Radu M
authors.initials: RM
authors.lastname: Nanau
mesh_terms: D052242:Adiponectin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D054439:Ghrelin / Q000097:blood; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D020738:Leptin / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood / Q000000981:diagnostic imaging; D008111:Liver Function Tests; D055432:Metabolomics; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000201:enzymology; D018384:Oxidative Stress; D040901:Proteomics; D014463:Ultrasonography
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D054439:Ghrelin; D053538:Keratin-18; D020738:Leptin