Untargeted metabolomics as a diagnostic tool in NAFLD: discrimination of steatosis, steatohepatitis and cirrhosis.

Autor: Masarone M; Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, 'Scuola Medica Salernitana', University of Salerno, Via Salvador Allende, 84081, Baronissi, SA, Italy., Troisi J; Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, 'Scuola Medica Salernitana', University of Salerno, Via Salvador Allende, 84081, Baronissi, SA, Italy.; Theoreo srl, Via degli Ulivi 3, 84090, Montecorvino Pugliano, SA, Italy.; European Biomedical Research Institute of Salerno (EBRIS), Via S. de Renzi, 3, 84125, Salerno, SA, Italy.; Hosmotic srl, Via R. Bosco 178, 80069, Vico Equense, NA, Italy., Aglitti A; Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, 'Scuola Medica Salernitana', University of Salerno, Via Salvador Allende, 84081, Baronissi, SA, Italy., Torre P; Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, 'Scuola Medica Salernitana', University of Salerno, Via Salvador Allende, 84081, Baronissi, SA, Italy., Colucci A; Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, 'Scuola Medica Salernitana', University of Salerno, Via Salvador Allende, 84081, Baronissi, SA, Italy.; Theoreo srl, Via degli Ulivi 3, 84090, Montecorvino Pugliano, SA, Italy., Dallio M; Hepatogastroenterology Division, University of Campania 'Luigi Vanvitelli', Via S Pansini 5, 80131, Naples, Italy., Federico A; Hepatogastroenterology Division, University of Campania 'Luigi Vanvitelli', Via S Pansini 5, 80131, Naples, Italy., Balsano C; MESVA Department, University of L'Aquila, Piazza S. Salvatore Tommasi 1, 67100, Coppito, L'Aquila, Italy.; F. Balsano Foundation, Via Giovanni Battista Martini 6, 00198, Rome, Italy., Persico M; Internal Medicine and Hepatology Unit, Department of Medicine, Surgery and Dentistry, 'Scuola Medica Salernitana', University of Salerno, Via Salvador Allende, 84081, Baronissi, SA, Italy. mpersico@unisa.it.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2021 Jan 16; Vol. 17 (2), pp. 12. Date of Electronic Publication: 2021 Jan 16.
DOI: 10.1007/s11306-020-01756-1
Abstrakt: Introduction: Non-Alcoholic Fatty Liver Disease encompasses a spectrum of diseases ranging from simple steatosis to steatohepatitis (or NASH), up to cirrhosis and hepatocellular carcinoma (HCC). The challenge is to recognize the more severe and/or progressive pathology. A reliable non-invasive method does not exist. Untargeted metabolomics is a novel method to discover biomarkers and give insights on diseases pathophysiology.
Objectives: We applied metabolomics to understand if simple steatosis, steatohepatitis and cirrhosis in NAFLD patients have peculiar metabolites profiles that can differentiate them among each-others and from controls.
Methods: Metabolomics signatures were obtained from 307 subjects from two separated enrollments. The first collected samples from 69 controls and 144 patients (78 steatosis, 23 NASH, 15 NASH-cirrhosis, 8 HCV-cirrhosis, 20 cryptogenic cirrhosis). The second, used as validation-set, enrolled 44 controls and 50 patients (34 steatosis, 10 NASH and 6 NASH-cirrhosis).The "Partial-Least-Square Discriminant-Analysis"(PLS-DA) was used to reveal class separation in metabolomics profiles between patients and controls and among each class of patients, and to reveal the metabolites contributing to class differentiation.
Results: Several metabolites were selected as relevant, in particular:Glycocholic acid, Taurocholic acid, Phenylalanine, branched-chain amino-acids increased at the increase of the severity of the disease from steatosis to NASH, NASH-cirrhosis, while glutathione decreased (p < 0.001 for each). Moreover, an ensemble machine learning (EML) model was built (comprehending 10 different mathematical models) to verify diagnostic performance, showing an accuracy > 80% in NAFLD clinical stages prediction.
Conclusions: Metabolomics profiles of NAFLD patients could be a useful tool to non-invasively diagnose NAFLD and discriminate among the various stages of the disease, giving insights into its pathophysiology.
Databáze: MEDLINE
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