title: Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis.
abstract: OBJECTIVE
  To identify plasma analytes using metabolomics that correlate with the diagnosis and severity of liver disease in patients with alcoholic hepatitis (AH).
  
  
  METHODS
  We prospectively recruited patients with cirrhosis from AH (n = 23) and those with cirrhosis with acute decompensation (AD) from etiologies other than alcohol (n = 25). We used mass spectrometry to identify 29 metabolic compounds in plasma samples from fasted subjects. A receiver operating characteristics analysis was performed to assess the utility of biomarkers in distinguishing acute AH from alcoholic cirrhosis. Logistic regression analysis was performed to build a predictive model for AH based on clinical characteristics. A survival analysis was used to construct Kaplan Meier curves evaluating transplant-free survival.
  
  
  RESULTS
  A comparison of model for end-stage liver disease (MELD)-adjusted metabolomics levels between cirrhosis patients who had AD or AH showed that patients with AH had significantly higher levels of betaine, and lower creatinine, phenylalanine, homocitrulline, citrulline, tyrosine, octenoyl-carnitine, and symmetric dimethylarginine. When considering combined levels, betaine and citrulline were highly accurate predictors for differentiation between AH and AD (area under receiver operating characteristics curve = 0.84). The plasma levels of carnitine [0.54 (0.18, 0.91); P = 0.005], homocitrulline [0.66 (0.34, 0.99); P < 0.001] and pentanoyl-carnitine [0.53 (0.16, 0.90); P = 0.007] correlated with MELD scores in patients diagnosed with AH. Increased levels of many biomarkers (carnitine P = 0.005, butyrobetaine P = 0.32, homocitrulline P = 0.002, leucine P = 0.027, valine P = 0.024, phenylalanine P = 0.037, tyrosine P = 0.012, acetyl-carnitine P = 0.006, propionyl-carnitine P = 0.03, butyryl-carnitine P = 0.03, trimethyl-lisine P = 0.034, pentanoyl-carnitine P = 0.03, hexanoyl-carnitine P = 0.026) were associated with increased mortality in patients with AH.
  
  
  CONCLUSIONS
  Metabolomics plasma analyte levels might be used to diagnose of AH or help predict patient prognoses.
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Mona
authors.initials: M
authors.lastname: Ascha
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Mustafa S
authors.initials: MS
authors.lastname: Ascha
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Raed
authors.initials: R
authors.lastname: Dweik
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Nizar N
authors.initials: NN
authors.lastname: Zein
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: David
authors.initials: D
authors.lastname: Grove
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: J Mark
authors.initials: JM
authors.lastname: Brown
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Marshall
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.affiliation: Mona Ascha, Mustafa S Ascha, Nizar N Zein, Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Hanouneh
keywords: Alcoholic hepatitis; Biomarkers; Cirrhosis; Liver biopsy; Liver disease; Metabolomics; Model for end-stage liver disease