title: Non-alcoholic steatohepatitis: a non-invasive diagnosis by analysis of exhaled breath.
abstract: OBJECTIVE
  Histological evaluation of a liver biopsy is the current gold standard to diagnose non-alcoholic steatohepatitis (NASH), but the procedure to obtain biopsies is associated with morbidity and high costs. Hence, only subjects at high risk are biopsied, leading to underestimation of NASH prevalence, and undertreatment. Since analysis of volatile organic compounds in breath has been shown to accurately identify subjects with other chronic inflammatory diseases, we investigated its potential as a non-invasive tool to diagnose NASH.
  
  
  METHODS
  Wedge-shaped liver biopsies from 65 subjects (BMI 24.8-64.3 kg/m(2)) were obtained during surgery and histologically evaluated. The profile of volatile organic compounds in pre-operative breath samples was analyzed by gas chromatography-mass spectrometry and related to liver histology scores and plasma parameters of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
  
  
  RESULTS
  Three exhaled compounds were sufficient to distinguish subjects with (n=39) and without NASH (n=26), with an area under the ROC curve of 0.77. The negative and positive predictive values were 82% and 81%. In contrast, elevated ALT levels or increased AST/ALT ratios both showed negative predictive values of 43%, and positive predictive values of 88% and 70%, respectively. The breath test reduced the hypothetical percentage of undiagnosed NASH patients from 67-79% to 10%, and of misdiagnosed subjects from 49-51% to 18%.
  
  
  CONCLUSIONS
  Analysis of volatile organic compounds in exhaled air is a promising method to indicate NASH presence and absence. In comparison to plasma transaminase levels, the breath test significantly reduced the percentage of missed NASH patients and the number of unnecessarily biopsied subjects.
authors.affiliation: Department of General Surgery, Nutrition and Toxicology Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Froukje J
authors.initials: FJ
authors.lastname: Verdam
authors.forename: Jan W
authors.initials: JW
authors.lastname: Dallinga
authors.forename: Ann
authors.initials: A
authors.lastname: Driessen
authors.forename: Charlotte
authors.initials: C
authors.lastname: de Jonge
authors.forename: Edwin J C
authors.initials: EJ
authors.lastname: Moonen
authors.forename: Joep B N
authors.initials: JB
authors.lastname: van Berkel
authors.forename: Jakobus
authors.initials: J
authors.lastname: Luijk
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Bouvy
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Sander S
authors.initials: SS
authors.lastname: Rensen
authors.forename: Jan Willem M
authors.initials: JW
authors.lastname: Greve
authors.forename: Frederik Jan
authors.initials: FJ
authors.lastname: van Schooten
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001944:Breath Tests; D005234:Fatty Liver / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D055549:Volatile Organic Compounds / Q000032:analysis
chemical_list: D055549:Volatile Organic Compounds; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase