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Clinical and Translational Medicine

, 5:33

First Online: 18 August 2016Received: 27 May 2016Accepted: 14 July 2016DOI: 10.1186-s40169-016-0109-2

Cite this article as: Sarfaraz, M.O., Myers, R.P., Coffin, C.S. et al. Clin Trans Med 2016 5: 33. doi:10.1186-s40169-016-0109-2

Abstract

BackgroundHigh-throughput technologies have the potential to identify non-invasive biomarkers of liver pathology and improve our understanding of basic mechanisms of liver injury and repair. A metabolite profiling approach was employed to determine associations between alterations in serum metabolites and liver histology in patients with chronic hepatitis C virus HCV infection.

MethodsSera from 45 non-diabetic patients with chronic HCV were quantitatively analyzed using H-NMR spectroscopy. A metabolite profile of advanced fibrosis METAVIR F3-4 was established using orthogonal partial least squares discriminant analysis modeling and validated using seven-fold cross-validation and permutation testing. Bioprofiles of moderate to severe steatosis ≥33 % and necroinflammation METAVIR A2-3 were also derived. The classification accuracy of these profiles was determined using areas under the receiver operator curves AUROCSs measuring against liver biopsy as the gold standard.

ResultsIn total 63 spectral features were profiled, of which a highly significant subset of 21 metabolites were associated with advanced fibrosis variable importance score >1 in multivariate modeling; R = 0.673 and Q = 0.285. For the identification of F3–4 fibrosis, the metabolite bioprofile had an AUROC of 0.86 95 % CI 0.74–0.97. The AUROCs for the bioprofiles for moderate to severe steatosis were 0.87 95 % CI 0.76–0.97 and for grade A2–3 inflammation were 0.73 0.57–0.89.

ConclusionThis proof-of-principle study demonstrates the utility of a metabolomics profiling approach to non-invasively identify biomarkers of liver fibrosis, steatosis and inflammation in patients with chronic HCV. Future cohorts are necessary to validate these findings.

KeywordsHepatitis C Metabolomics H-NMR spectroscopy AbbreviationsHCVhepatitis C virus

AUROCarea under the receiver operator curve

H-NMRproton-nuclear magnetic resonance

SVRsustained virological response

APRIAST to platelet ratio

HCChepatocellulat carcinoma

HIVhuman immunodeficiency virus

Ffibrosis

Anecroinflammation

CHREBconjoint health research ethics board

ALTalanine-aminotransferase

ASTaspartate-aminotransferase

BMIbody mass index

NAFLDnon-alcoholic fatty liver disease

PCAprincipal component analysis

OPLSDAorthogonol partial least squared discriminant analysis

ANOVAanalysis of variance

VIPvariables importance in projection

HMDBhuman metabolome database

PPVpositive predictive value

NPVnegative predictive value

FIB-4fibrosis-4

GCAglycolic acid

TCAtaurocholic acid

M. Omair Sarfaraz and Robert P. Myers contributed equally to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s40169-016-0109-2 contains supplementary material, which is available to authorized users.

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Autor: M. Omair Sarfaraz - Robert P. Myers - Carla S. Coffin - Zu-Hua Gao - Abdel Aziz M. Shaheen - Pam M. Crotty - Ping Zha

Fuente: https://link.springer.com/







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