title: Non-invasive separation of alcoholic and non-alcoholic liver disease with predictive modeling.
abstract: OBJECTIVE
  Currently, a major clinical challenge is to distinguish between chronic liver disease caused by metabolic syndrome (non-alcoholic fatty liver disease, NAFLD) from that caused by long term or excessive alcohol consumption (ALD). The etiology of severe liver disease affects treatment options and priorities for liver transplantation and organ allocation. Thus we compared physiologically similar NAFLD and ALD patients to detect biochemical differences for improved separation of these mechanistically overlapping etiologies.
  
  
  METHODS
  In a cohort of 31 NAFLD patients with BMI below 30 and a cohort of ALD patient with (ALDC n = 51) or without cirrhosis (ALDNC n = 51) serum transaminases, cell death markers and (adipo-)cytokines were assessed. Groups were compared with One-way ANOVA and Tukey's correction. Predictive models were built by machine learning techniques.
  
  
  RESULTS
  NAFLD, ALDNC or ALDC patients did not differ in demographic parameters. The ratio of alanine aminotransferase/aspartate aminotransferase--common serum parameters for liver damage--was significantly higher in the NAFLD group compared to both ALD groups (each p<0.0001). Adiponectin and tumor necrosis factor(TNF)-alpha were significantly lower in NAFLD than in ALDNC (p<0.05) or ALDC patients (p<0.0001). Significantly higher serum concentrations of cell death markers, hyaluronic acid, adiponectin, and TNF-alpha (each p<0.0001) were found in ALDC compared to ALDNC. Using machine learning techniques we were able to discern NAFLD and ALDNC (up to an AUC of 0.9118±0.0056) or ALDC and ALDNC (up to an AUC of 0.9846±0.0018), respectively.
  
  
  CONCLUSIONS
  Machine learning techniques relying on ALT/AST ratio, adipokines and cytokines distinguish NAFLD and ALD. In addition, severity of ALD may be non-invasively diagnosed via serum cytokine concentrations.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Sowa
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany; Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Atmaca
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Alisan
authors.initials: A
authors.lastname: Kahraman
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlattjan
authors.affiliation: LVR-Clinic, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Lindner
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Sydor
authors.affiliation: LVR-Clinic, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Scherbaum
authors.affiliation: Institute for Pathology, Medical University Graz, Graz, Austria.
authors.forename: Karoline
authors.initials: K
authors.lastname: Lackner
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.affiliation: Department of Bioinformatics, Straubing Center of Science, Straubing, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Heider
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, Kentucky, United States of America.
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Arteel
authors.affiliation: LVR-Clinic, University Hospital, University Duisburg-Essen, Essen, Germany; Psychosomatic and Psychotherapeutic Department, University Hospital Erlangen, Erlangen, Germany.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Erim
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood; D000410:Alanine Transaminase / Q000097:blood*; D001185:Artificial Intelligence; D001219:Aspartate Aminotransferases / Q000097:blood*; D015331:Cohort Studies; D003198:Computer Simulation; D016207:Cytokines / Q000097:blood*; D005235:Fatty Liver, Alcoholic / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054392:Adipokines; D052242:Adiponectin; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase