title: Metabolomics discloses potential biomarkers for the noninvasive diagnosis of idiopathic portal hypertension.
abstract: OBJECTIVE
  Idiopathic portal hypertension (IPH) is a rare cause of portal hypertension that lacks a specific diagnostic test. Requiring ruling-out other causes of portal hypertension it is frequently misdiagnosed. This study evaluates whether using high-throughput techniques there is a metabolomic profile allowing a noninvasive diagnosis of IPH.
  
  
  METHODS
  Thirty-three IPH patients were included. Matched patients with cirrhosis (CH) and healthy volunteers (HV) were included as controls. Metabolomic analysis of plasma samples was performed using UPLC-time-of-flight-mass spectrometry. We computed Student's P-values, corrected by multiple comparison and VIP score (Variable Importance in the Projection). The metabolites were selected with an adjusted Benjamini Hochberg P value <0.05. We use markers with a greater VIP score, to build partial least squares projection to latent structures regression with discriminant analysis (PLS-DA) representative models to discriminate IPH from CH and from HV. The performance of the PLS-DA model was evaluated using R(2) and Q(2) parameter. An additional internal cross-validation was done.
  
  
  RESULTS
  PLS-DA analysis showed a clear separation of IPH from CH with a model involving 28 metabolites (Q(2)=0.67, area under the curve (AUC)=0.99) and a clear separation of IPH from healthy subjects with a model including 31 metabolites (Q(2)=0.75, AUC=0.98). After cross-validation, both models showed high rates of sensitivity (94.8 and 97.5), specificity (89.1 and 89.7), and AUC (0.98 and 0.98), reinforcing the strength of our findings.
  
  
  CONCLUSIONS
  A metabolomic profile clearly differentiating patients with IPH from CH and healthy subjects has been identified using subsets of 28 and 31 metabolites, respectively. Therefore, metabolomic analysis appears to be a valuable tool for the noninvasive diagnosis of IPH.
authors: Liver Unit, Hepatic Hemodynamic Laboratory, Institut de Malalties Digestives i Metaboliques, Hospital Clínic-Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors: Susana
authors: S
authors: Seijo
authors: Juan Jose
authors: JJ
authors: Lozano
authors: Cristina
authors: C
authors: Alonso
authors: Enric
authors: E
authors: Reverter
authors: Rosa
authors: R
authors: Miquel
authors: Juan G
authors: JG
authors: Abraldes
authors: Maria Luz
authors: ML
authors: Martinez-Chantar
authors: Angeles
authors: A
authors: Garcia-Criado
authors: Annalisa
authors: A
authors: Berzigotti
authors: Azucena
authors: A
authors: Castro
authors: Jose M
authors: JM
authors: Mato
authors: Jaume
authors: J
authors: Bosch
authors: Juan Carlos
authors: JC
authors: Garcia-Pagan
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood* / Q000175:diagnosis*; D008103:Liver Cirrhosis / Q000097:blood; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D015415:Biomarkers