title: Metabolomics as a diagnostic tool for idiopathic non-cirrhotic portal hypertension.
abstract: Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare life-threatening liver disease that lacks a specific diagnostic test being frequently misdiagnosed as cryptogenic cirrhosis. Preliminary data from our group identified a plasma metabolomic profile able to differentiate INCPH from patients with cirrhosis (CH) and healthy volunteers (HV). However, the untargeted methodology applied was unable to identify all the specific metabolites, hampering the possibility of building-up diagnostic models. This study applies a wide-coverage of previously identified metabolites through a high-throughput metabolomics technology, evaluating if there is a metabolomic profile that allows a non-invasive diagnosis of INCPH.
  
  
  
  We included 34 patients with INCPH, 34 with CH and 34 HV. We performed a targeted metabolomic analysis of serum samples using UPLC-MS. The best combination of a set of specific metabolites was obtained using stepwise logistic regression (LR) and recursive partitioning analysis (RPA).
  
  
  
  After internal cross-validation, LR analysis identified a subset of 5-metabolites that clearly differentiate INCPH patients from CH and HV (average corrected optimism AUROC = 0.8871 [0.838-0.924]). Using high and low cut-off values the model has an excellent capacity to respectively diagnose or exclude INCPH. The RPA analysis strategy used the 3-metabolites signature differentiating INCPH from CH and the 2-metabolites signature differentiating INCPH from HV. A decision tree applying sequentially these metabolic profiles diagnosed 88% of INCPH patients.
  
  
  
  Different metabolomic profiles allow the diagnosis of INCPH with high specificity and sensibility and may represent excellent clinical tools for its diagnosis avoiding multiple and invasive tests.
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Seijo
authors.affiliation: Bioinformatic Platform, CIBERehd, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Lozano
authors.affiliation: OWL, Parque Tecnológico de Bizkaia, Bizkaia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alonso
authors.affiliation: Pathology Deparment, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Miquel
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Berzigotti
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Enric
authors.initials: E
authors.lastname: Reverter
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Fanny
authors.initials: F
authors.lastname: Turon
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.|CIC bioGUNE, Bizkaia, Spain.
authors.forename: Mari Luz
authors.initials: ML
authors.lastname: Martínez-Chantar
authors.affiliation: OWL, Parque Tecnológico de Bizkaia, Bizkaia, Spain.
authors.forename: Azucena
authors.initials: A
authors.lastname: Castro
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.|CIC bioGUNE, Bizkaia, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Mato
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Hernández-Gea
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Jaume
authors.initials: J
authors.lastname: Bosch
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Pagán
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006975:Hypertension, Portal / Q000175:diagnosis*; D008103:Liver Cirrhosis / Q000175:diagnosis; D016015:Logistic Models; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D008954:Models, Biological; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013030:Spain
keywords: cirrhosis; hepatoportal sclerosis; metabolomics; non-cirrhotic portal hypertension