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  • Title: Metabolomics discloses potential biomarkers for the noninvasive diagnosis of idiopathic portal hypertension.
    Author: Seijo S, Lozano JJ, Alonso C, Reverter E, Miquel R, Abraldes JG, Martinez-Chantar ML, Garcia-Criado A, Berzigotti A, Castro A, Mato JM, Bosch J, Garcia-Pagan JC.
    Journal: Am J Gastroenterol; 2013 Jun; 108(6):926-32. PubMed ID: 23419380.
    Abstract:
    OBJECTIVES: 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.
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