title: Metabolic Characterization of Advanced Liver Fibrosis in HCV Patients as Studied by Serum 1H-NMR Spectroscopy.
abstract: Several etiologies result in chronic liver diseases including chronic hepatitis C virus infection (HCV). Despite its high incidence and the severe economic and medical consequences, liver disease is still commonly overlooked due to the lack of efficient non-invasive diagnostic methods. While several techniques have been tested for the detection of fibrosis, the available biomarkers still present severe limitations that preclude their use in clinical diagnostics. Liver diseases have also been the subject of metabolomic analysis. Here, we demonstrate the suitability of 1H NMR spectroscopy for characterizing the metabolism of liver fibrosis induced by HCV. Serum samples from HCV patients without fibrosis or with liver cirrhosis were analyzed by NMR spectroscopy and the results were submitted to multivariate and univariate statistical analysis. PLS-DA test was able to discriminate between advanced fibrotic and non-fibrotic patients and several metabolites were found to be up or downregulated in patients with cirrhosis. The suitability of the most significantly regulated metabolites was validated by ROC analysis. Our study reveals that choline, acetoacetate and low-density lipoproteins are the most informative biomarkers for predicting cirrhosis in HCV patients. Our results demonstrate that statistical analysis of 1H-NMR spectra is able to distinguish between fibrotic and non-fibrotic patients suffering from HCV, representing a novel diagnostic application for NMR spectroscopy.
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: Nieves
authors.initials: N
authors.lastname: Embade
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Mariño
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: Tammo
authors.initials: T
authors.lastname: Diercks
authors.affiliation: ONE WAY LIVER METABOLOMICS SL, Derio, Bizkaia, Spain.
authors.forename: Ainara
authors.initials: A
authors.lastname: Cano
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Sabela
authors.initials: S
authors.lastname: Lens
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Cabrera
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Navasa
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Bizkaia, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Falcón-Pérez
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Caballería
authors.affiliation: ONE WAY LIVER METABOLOMICS SL, Derio, Bizkaia, Spain.
authors.forename: Azucena
authors.initials: A
authors.lastname: Castro
authors.affiliation: Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, 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: CIC bioGUNE, Derio, Bizkaia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Mato
authors.affiliation: CIC bioGUNE, Derio, Bizkaia, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Millet
mesh_terms: D000328:Adult; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D066244:Proton Magnetic Resonance Spectroscopy