title: The breathprints in patients with liver disease identify novel breath biomarkers in alcoholic hepatitis.
abstract: OBJECTIVE
  Selected-ion flow-tube mass spectrometry can precisely identify trace gases in the human breath, in the parts-per-billion range. We investigated whether concentrations of volatile compounds in breath samples correlate with the diagnosis of alcoholic hepatitis (AH) and the severity of liver disease in patients with AH.
  
  
  METHODS
  We recruited patients with liver disease from a single tertiary care center. The study population was divided between those with AH with cirrhosis (n = 40) and those with cirrhosis with acute decompensation from etiologies other than alcohol (n = 40); individuals without liver disease served as control subjects (n = 43). We used selected-ion flow-tube mass spectrometry to identify and measure 14 volatile compounds in breath samples from fasted subjects. We used various statistical analyses to compare clinical characteristics and breath levels of compounds among groups and to test the correlation between levels of compounds and severity of liver disease. Logistic regression analysis was performed to build a predictive model for AH.
  
  
  RESULTS
  We identified 6 compounds (2-propanol, acetaldehyde, acetone, ethanol, pentane, and trimethylamine [TMA]) whose levels were increased in patients with liver disease compared with control subjects. Mean concentrations of TMA and pentane (TAP) were particularly high in breath samples from patients with AH, compared with those with acute decompensation or control subjects (for both, P < .001). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of AH based on breath levels of TAP. TAP scores of 36 or higher identified the patients with AH (area under the receiver operating characteristic curves = 0.92) with 90% sensitivity and 80% specificity. The levels of exhaled TMA had a low level of correlation with the severity of AH based on model for end-stage liver disease score (r = 0.38; 95% confidence interval, 0.07-0.69; P = .018).
  
  
  CONCLUSIONS
  Based on levels of volatile compounds in breath samples, we can identify patients with AH vs patients with acute decompensation or individuals without liver disease. Levels of exhaled TMA moderately correlate with the severity of AH. These findings might be used in diagnosis of AH or in determining patient prognosis.
authors.affiliation: Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Hanouneh
authors.affiliation: Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Zein
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine/Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Frank
authors.initials: F
authors.lastname: Cikach
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine/Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Luma
authors.initials: L
authors.lastname: Dababneh
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine/Respiratory Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: David
authors.initials: D
authors.lastname: Grove
authors.affiliation: Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Naim
authors.initials: N
authors.lastname: Alkhouri
authors.affiliation: Department of Quantitative Health Science, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Department of Pulmonary, Allergy, and Critical Care Medicine/Respiratory Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address: DWEIKR@ccf.org.
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D001944:Breath Tests / Q000379:methods*; D005260:Female; D006519:Hepatitis, Alcoholic / Q000175:diagnosis*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D012720:Severity of Illness Index; D062606:Tertiary Care Centers; D055549:Volatile Organic Compounds / Q000032:analysis*
chemical_list: D015415:Biomarkers; D055549:Volatile Organic Compounds
keywords: Alcohol Consumption; Liver Damage; Marker Panel; Microbiota
references.citation: Drug Metab Dispos. 2001 Apr;29(4 Pt 2):517-21
references.pmid: 11259343
references.citation: Hepatology. 2009 Aug;50(2):638-44
references.pmid: 19575462
references.citation: N Engl J Med. 2009 Jun 25;360(26):2758-69
references.pmid: 19553649
references.citation: Science. 1974 Jan 18;183(4121):208-10
references.pmid: 4808857
references.citation: Acta Med Scand. 1956 Feb 29;153(6):433-41
references.pmid: 13313056
references.citation: J Clin Invest. 1999 Sep;104(6):805-13
references.pmid: 10491416
references.citation: J Hepatol. 1997 Jun;26(6):1372-8
references.pmid: 9210626
references.citation: Mutat Res. 2006 Jun;612(3):165-171
references.pmid: 16481213
references.citation: Hepatology. 1998 Nov;28(5):1318-26
references.pmid: 9794917
references.citation: Mass Spectrom Rev. 2005 Sep-Oct;24(5):661-700
references.pmid: 15495143
references.citation: F1000 Med Rep. 2010 Jul 22;2:56
references.pmid: 21173863
references.citation: Nature. 2011 Apr 7;472(7341):57-63
references.pmid: 21475195
references.citation: Food Chem Toxicol. 1999 May;37(5):515-20
references.pmid: 10456680
references.citation: BMC Res Notes. 2008 Jul 10;1:41
references.pmid: 18710494
references.citation: Gastrointest Endosc. 1996 Jun;43(6):568-71
references.pmid: 8781934
references.citation: Scand J Gastroenterol. 1999 May;34(5):524-8
references.pmid: 10423071
references.citation: Gastroenterology. 2008 May;134(6):1670-81
references.pmid: 18471546
references.citation: Z Gastroenterol. 1997 Aug;35(8):609-14
references.pmid: 9297776
references.citation: Rapid Commun Mass Spectrom. 2010 Jun 30;24(12):1763-9
references.pmid: 20499321