Untargeted metabolomics as a diagnostic tool in NAFLD: discrimination of steatosis, steatohepatitis and cirrhosis.
Metabolomics
; 17(2): 12, 2021 01 16.
Article
en En
| MEDLINE
| ID: mdl-33458794
ABSTRACT
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 particularGlycocholic 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metabolómica
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Hígado Graso
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Enfermedad del Hígado Graso no Alcohólico
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Cirrosis Hepática
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Metabolomics
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia