R. C. Bone, R. A. Balk, F. B. Cerra, R. P. Dellinger, A. M. Fein et al., DEFINITIONS FOR SEPSIS AND ORGAN FAILURE AND GUIDELINES FOR THE USE OF INNOVATIVE THERAPIES IN SEPSIS. Chest, vol.101, issue.6, pp.1644-55, 1992.

M. M. Levy, M. P. Fink, J. C. Marshall, A. E. Angus, D. Cook et al., SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference, vol.31, pp.1250-1256, 2001.

R. A. Balk, Pathogenesis and management of multiple organ dysfunction or failure in severe sepsis and septic shock, Crit Care Clin, vol.16, issue.2, p.337, 2000.

E. Rivers, B. Nguyen, S. Havstad, J. Ressler, A. Muzzin et al., Early goal-directed therapy in the treatment of severe sepsis and septic shock, New Engl J Med, vol.345, pp.1368-77, 2001.

R. P. Dellinger, M. M. Levy, J. M. Carlet, J. Bion, M. M. Parker et al., Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock, Crit Care Med, vol.36, issue.1, pp.296-327, 2008.

J. L. Vincent, A. De-mendonca, F. Cantraine, R. Moreno, J. Takala et al., Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, prospective study, Crit Care Med, vol.26, issue.11, pp.1793-800, 1998.

W. J. Lee, S. H. Woo, D. H. Kim, S. H. Seol, S. K. Park et al., Are prognostic scores and biomarkers such as procalcitonin the appropriate prognostic precursors for elderly patients with sepsis in the emergency department?, Aging Clin Exp Res, vol.28, issue.5, pp.917-941, 2016.

B. Mickiewicz, H. J. Vogel, H. R. Wong, and B. W. Winston, Metabolomics as a novel approach for early diagnosis of pediatric septic shock and its mortality, Am J Respir Crit Care Med, vol.187, issue.9, pp.967-76, 2013.

P. J. Foxall, M. Spraul, R. D. Farrant, L. C. Lindon, G. H. Neild et al., 750 MHz 1H-NMR spectroscopy of human blood plasma, J Pharm Biomed Anal, vol.11, issue.4-5, pp.267-76, 1993.

F. Delaglio, S. Grzesiek, G. W. Vuister, G. Zhu, J. Pfeifer et al., NMRPipe: a multidimensional spectral processing system based on UNIX pipes, J Biomol Nmr, vol.6, issue.3, pp.277-93, 1995.

F. Dieterle, A. Ross, G. Schlotterbeck, and H. Senn, Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics, Anal Chem, vol.78, issue.13, pp.4281-90, 2006.

J. A. Westerhuis, H. Hoefsloot, S. Smit, D. J. Vis, A. K. Smilde et al., Assessment of PLSDA cross validation, Metabolomics, 2008.

J. A. Westerhuis, E. J. Van-velzen, H. C. Hoefsloot, and A. K. Smilde, Multivariate paired data analysis: multilevel PLSDA versus OPLSDA, Metabolomics, 2010.
DOI : 10.1007/s11306-009-0185-z

URL : https://link.springer.com/content/pdf/10.1007%2Fs11306-009-0185-z.pdf

S. Kim, A. Pierro, M. Zamparelli, L. Spitz, and S. Eaton, Fatty acid oxidation in neonatal hepatocytes: effects of sepsis and glutamine, Nutrition, vol.18, issue.4, pp.298-300, 2002.

E. Nava, R. Palmer, and S. Moncada, Inhibition of nitric oxide synthesis in septic shock: how much is beneficial? The Lancet, vol.338, pp.1555-1562, 1991.

B. Wang, G. Chen, Y. Cao, J. Xue, J. Li et al., Correlation of lactate/albumin ratio level to organ failure and mortality in severe sepsis and septic shock, J Crit Care, vol.30, issue.2, pp.271-276, 2015.

W. R. Parrish, M. Rosas-ballina, M. Gallowitsch-puerta, M. Ochani, K. Ochani et al., Modulation of TNF release by choline requires alpha7 subunit nicotinic acetylcholine receptor-mediated signaling

, Mol Med, vol.14, issue.9, pp.567-74, 2008.

S. S. Waikar, K. D. Liu, and G. M. Chertow, Diagnosis, epidemiology and outcomes of acute kidney injury, Clin J Am Soc Nephrol, vol.3, issue.3, pp.844-61, 2008.

, Chinese Academy of Sciences, vol.116023

, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, vol.7244, p.93017

, Hepatology service, Jean Verdier Teaching Hospital, AP-HP, vol.93140

. Inserm-u1162, Gé nomique Fonctionnelle des Tumeurs solides, INSERM U1162

, Intensive Care Unit, Jean Verdier Teaching Hospital, AP-HP, vol.93140

. Aphp and . Service-d'anatomie-pathologique, Hôpital Jean Verdier

, Centre de Ressources Biologiques Maladies du foie. Groupe Hospitalier

, Centre de Ressources Biologiques Maladies du foie

. Aphp, J. De-radiologie, and . Verdier,

. Prof and . Dr, Philippe Savarin

. Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques, vol.7244

. Prof, . Dr, and . Xu, xugw@dicp.ac.cn References 1. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. The Lancet, vol.362, issue.9399, pp.1907-1924, 2003.

J. M. Llovet and J. Bruix, Novel advancements in the management of hepatocellular carcinoma in 2008, J Hepatol, vol.48, issue.1, pp.20-37, 2008.

L. L. Wong, W. M. Limm, R. Severino, and L. M. Wong, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International, Liver Transplantation Society, vol.6, issue.3, pp.320-325, 2000.

A. Facciorusso, V. Del-prete, A. M. Neve, V. Amoruso, A. Crucinio et al., Conditional survival analysis of hepatocellular carcinoma patients treated with radiofrequency ablation

, Hepatol Res, vol.45, issue.10, pp.62-72, 2015.

T. Livraghi, S. N. Goldberg, S. Lazzaroni, F. Meloni, L. Solbiati et al., Small hepatocellular carcinoma: Treatment with radio-frequency ablation versus ethanol injection, Radiology, vol.210, issue.3, pp.655-61, 1999.
DOI : 10.1148/radiology.210.3.r99fe40655

H. B. El-serag, Epidemiology of viral hepatitis and hepatocellular carcinoma, Gastroenterology, vol.142, issue.6, pp.1264-73, 2012.

M. Levrero, Viral hepatitis and liver cancer: the case of hepatitis C, Oncogene, vol.25, issue.27, pp.3834-3881, 2006.

F. Donato, A. Tagger, U. Gelatti, G. Parrinello, P. Boffetta et al., Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women, Am J Epidemiol, vol.155, issue.4, pp.323-354, 2002.

F. Buonfiglioli, F. Conti, P. Andreone, C. Crespi, F. Foschi et al., Development of hepatocellular carcinoma in HCV cirrhotic patients treated with direct acting antivirals, J Hepatol, vol.64, issue.2, p.215, 2016.

H. B. El-serag, J. A. Marrero, L. Rudolph, and K. R. Reddy, Diagnosis and treatment of hepatocellular carcinoma, Gastroenterology, vol.134, issue.6, pp.1752-63, 2008.

M. Mamas, W. B. Dunn, L. Neyses, and R. Goodacre, The role of metabolites and metabolomics in clinically applicable biomarkers of disease, Arch Toxicol, vol.85, issue.1, pp.5-17, 2011.

J. Xia, D. I. Broadhurst, M. Wilson, and D. S. Wishart, Translational biomarker discovery in clinical metabolomics: an introductory tutorial, Metabolomics, vol.9, issue.2, pp.280-99, 2013.

L. Zhou, L. Ding, P. Yin, X. Lu, X. Wang et al., Serum metabolic profiling study of hepatocellular carcinoma infected with hepatitis B or hepatitis C virus by using liquid chromatography-mass spectrometry, Journal of proteome research, vol.11, issue.11, pp.5433-5475, 2012.

J. Zeng, P. Yin, Y. Tan, L. Dong, C. Hu et al., Metabolomics study of hepatocellular carcinoma: discovery and validation of serum potential biomarkers by using capillary electrophoresis-mass spectrometry, Journal of proteome research, vol.13, issue.7, pp.3420-3451, 2014.

P. Nahon, R. Amathieu, M. N. Triba, N. Bouchemal, J. C. Nault et al., Identification of serum proton NMR metabolomic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis, Clin Cancer Res, vol.18, issue.24, pp.6714-6736, 2012.

L. Zhou, Y. Liao, P. Yin, Z. Zeng, J. Li et al., Metabolic profiling study of early and late recurrence of hepatocellular carcinoma based on liquid chromatography-mass spectrometry, J Chromatogr B Analyt Technol Biomed Life Sci, vol.966, pp.163-70, 2014.

M. R. Nezami-ranjbar, Y. Luo, D. Poto, C. Varghese, R. S. Ferrarini et al., GC-MS Based Plasma Metabolomics for Identification of Candidate Biomarkers for Hepatocellular Carcinoma in Egyptian Cohort, PloS one, vol.10, issue.6, p.127299, 2015.

A. I. Fitian, D. R. Nelson, C. Liu, Y. Xu, M. Ararat et al., Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS, Liver international : official journal of the International Association for the Study of the Liver, vol.34, issue.9, pp.1428-1472, 2014.

A. Budhu, S. Roessler, X. Zhao, Z. Yu, M. Forgues et al., Integrated metabolite and gene expression profiles identify lipid biomarkers associated with progression of hepatocellular carcinoma and patient outcomes, Gastroenterology, vol.144, issue.5, pp.1066-75, 2013.

T. Chen, G. Xie, X. Wang, J. Fan, Y. Qiu et al., Serum and Urine Metabolite Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma, Molecular & Cellular Proteomics, vol.10, issue.7, 2011.

A. D. Patterson, O. Maurhofer, D. Beyoglu, C. Lanz, K. W. Krausz et al., Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics and lipid profiling, Cancer Res, vol.71, issue.21, pp.6590-600, 2011.

H. Wu, R. Xue, L. Dong, T. Liu, C. Deng et al., Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry, Anal Chim Acta, vol.648, issue.1, pp.98-104, 2009.

C. Goossens, P. Nahon, L. Moyec, L. Triba, M. N. Bouchemal et al., Sequential Serum Metabolomic Profiling after Radiofrequency Ablation of Hepatocellular Carcinoma Reveals Different Response Patterns According to Etiology, Journal of proteome research, vol.15, issue.5, pp.1446-54, 2016.

V. M. Asiago, L. Z. Alvarado, N. Shanaiah, G. Gowda, K. Owusu-sarfo et al., Early Detection of Recurrent Breast Cancer Using Metabolite Profiling, Cancer Res, vol.70, issue.21, pp.8309-8327, 2010.

M. D. Cao, B. Sitter, T. F. Bathen, A. Bofin, P. E. Lonning et al., Predicting long-term survival and treatment response in breast cancer patients receiving neoadjuvant chemotherapy by MR metabolic profiling, Nmr Biomed, vol.25, issue.2, pp.369-78, 2012.

P. C. Calder, Omega-3 fatty acids and inflammatory processes, Nutrients, vol.2, issue.3, pp.355-74, 2010.
DOI : 10.1111/j.1365-2125.2012.04374.x

URL : https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.2012.04374.x

H. C. Li, H. C. Ma, C. H. Yang, and S. Y. Lo, Production and pathogenicity of hepatitis C virus core gene products, World J Gastroenterol, vol.20, issue.23, pp.7104-7126, 2014.

E. Lima-cabello, M. V. Garcia-mediavilla, M. E. Miquilena-colina, J. Vargas-castrillon, T. Lozanorodriguez et al., Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C, Clin Sci (Lond), vol.120, issue.6, pp.239-50, 2011.

E. R. Nelson, S. E. Wardell, J. S. Jasper, S. Park, S. Suchindran et al., 27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology, Science, vol.342, issue.6162, pp.1094-1102, 2013.
DOI : 10.1126/science.1241908

URL : http://europepmc.org/articles/pmc3899689?pdf=render

B. Roe, E. Kensicki, R. Mohney, and W. W. Hall, Metabolomic Profile of Hepatitis C Virus-Infected Hepatocytes, PloS one, vol.6, issue.8, p.23641, 2011.

A. Nath, I. Li, L. R. Roberts, and C. Chan, Elevated free fatty acid uptake via CD36 promotes epithelialmesenchymal transition in hepatocellular carcinoma, Sci Rep, vol.5, p.14752, 2015.

G. Ye, B. Zhu, Z. Yao, P. Yin, X. Lu et al., Analysis of urinary metabolic signatures of early hepatocellular carcinoma recurrence after surgical removal using gas chromatography-mass spectrometry, Journal of proteome research, vol.11, issue.8, pp.4361-72, 2012.

M. G. Vander-heiden, L. C. Cantley, and C. B. Thompson, Understanding the Warburg effect: the metabolic requirements of cell proliferation, Science, vol.324, issue.5930, pp.1029-1062, 2009.

A. Arzumanyan, H. M. Reis, and M. A. Feitelson, Pathogenic mechanisms in HBV-and HCV-associated hepatocellular carcinoma, Nature reviews Cancer, vol.13, issue.2, pp.123-158, 2013.

R. J. Deberardinis and T. Cheng, Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer, Oncogene, vol.29, issue.3, pp.313-337, 2010.

J. Long, H. Wang, Z. Lang, T. Wang, M. Long et al., Expression level of glutamine synthetase is increased in hepatocellular carcinoma and liver tissue with cirrhosis and chronic hepatitis B, Hepatology international, vol.5, issue.2, pp.698-706, 2011.

B. Zhang, L. W. Dong, Y. X. Tan, J. Zhang, Y. F. Pan et al., Asparagine synthetase is an independent predictor of surgical survival and a potential therapeutic target in hepatocellular carcinoma, Br J Cancer, vol.109, issue.1, pp.14-23, 2013.

F. Loayza-puch, K. Rooijers, L. C. Buil, J. Zijlstra, O. Vrielink et al., Tumour-specific proline vulnerability uncovered by differential ribosome codon reading, Nature, vol.530, issue.7591, pp.490-494, 2016.

V. De-giorgi, L. Buonaguro, A. Worschech, M. L. Tornesello, F. Izzo et al., Molecular Signatures Associated with HCV-Induced Hepatocellular Carcinoma and Liver Metastasis, PloS one, vol.8, issue.2, p.56153, 2013.

P. Song, Y. Inagaki, Z. Wang, K. Hasegawa, Y. Sakamoto et al., High Levels of GammaGlutamyl Transferase and Indocyanine Green Retention Rate at 15 min as Preoperative Predictors of Tumor Recurrence in Patients With Hepatocellular Carcinoma, Medicine (Baltimore), vol.94, issue.21, p.810, 2015.

R. T. Poon, S. T. Fan, I. O. Ng, C. M. Lo, C. L. Liu et al., Different risk factors and prognosis for early and late intrahepatic recurrence after resection of hepatocellular carcinoma, Cancer, vol.89, issue.3, pp.500-507, 2000.

D. Zhao, S. W. Zou, Y. Liu, X. Zhou, Y. Mo et al., Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer, Cancer cell, vol.23, issue.4, pp.464-76, 2013.

D. N. Wheatley, R. Kilfeather, A. Stitt, and E. Campbell, Integrity and stability of the citrulline-arginine pathway in normal and tumour cell lines, Cancer Lett, vol.227, issue.2, pp.141-52, 2005.

, Appendix 2: Supporting information of the HCC-related study

L. -asparagine,-l-aspartate,-l-cysteine,-l-glutamine,-l-glutamate,-l-isoleucine,-l-leucine,-l-proline,-l-threonine,-l-serine, L. -tryptophan, and N. ,

, hexanoic acid (FFA 6:0), decanoic acid (FFA 10:0), dodecanoic acid (FFA 12:0), pentadecanoic acid (FFA 15:0), palmitic acid (FFA 16:0), octadecanoic acid (FFA 18:0), 11-Eicosenoic acid, Arachidonic acid (FFA 20:4) and Docosahexaenoic acid, vol.20

J. K. Nicholson, J. C. Lindon, and E. Holmes, Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data, Xenobiotica, vol.29, issue.11, pp.1181-1190, 1999.

O. Fiehn, Metabolomics-the link between genotypes and phenotypes, Plant Mol Biol, vol.48, issue.1-2, pp.155-71, 2002.

J. K. Nicholson and J. C. Lindon, Systems biology: metabonomics, Nature, vol.455, issue.7216, pp.1054-1060, 2008.

S. Rochfort, Metabolomics reviewed: a new "omics" platform technology for systems biology and implications for natural products research, J Nat Prod, vol.68, issue.12, pp.1813-1833, 2005.
DOI : 10.1021/np050255w

K. Dettmer, P. A. Aronov, and B. D. Hammock, Mass spectrometry-based metabolomics, Mass Spectrom Rev, vol.26, issue.1, pp.51-78, 2007.

R. Madsen, T. Lundstedt, and J. Trygg, Chemometrics in metabolomics-a review in human disease diagnosis, Anal Chim Acta, vol.659, issue.1, pp.23-33, 2010.

M. Mamas, W. B. Dunn, L. Neyses, and R. Goodacre, The role of metabolites and metabolomics in clinically applicable biomarkers of disease, Arch Toxicol, vol.85, issue.1, pp.5-17, 2011.

G. N. Gowda, S. Zhang, H. Gu, V. Asiago, N. Shanaiah et al., Metabolomics-based methods for early disease diagnostics. Expert review of molecular diagnostics, vol.8, pp.617-650, 2008.
DOI : 10.1586/14737159.8.5.617

URL : http://europepmc.org/articles/pmc3890417?pdf=render

S. R. Gill, M. Pop, R. T. Deboy, P. B. Eckburg, P. J. Turnbaugh et al., Metagenomic analysis of the human distal gut microbiome, Science, vol.312, issue.5778, pp.1355-1364, 2006.

J. G. Bundy, M. P. Davey, and M. R. Viant, Environmental metabolomics: a critical review and future perspectives, Metabolomics, vol.5, issue.1, pp.3-21, 2009.
DOI : 10.1007/s11306-008-0152-0

L. W. Sumner, P. Mendes, and R. A. Dixon, Plant metabolomics: large-scale phytochemistry in the functional genomics era, Phytochemistry, vol.62, issue.6, pp.817-853, 2003.

L. Shyur and Y. , Metabolomics for phytomedicine research and drug development, Curr Opin Chem Biol, vol.12, issue.1, pp.66-71, 2008.
DOI : 10.1016/j.cbpa.2008.01.032

M. J. Gibney, M. Walsh, L. Brennan, H. M. Roche, B. German et al., Metabolomics in human nutrition: opportunities and challenges. The American journal of clinical nutrition, vol.82, pp.497-503, 2005.
DOI : 10.1093/ajcn.82.3.497

URL : https://academic.oup.com/ajcn/article-pdf/82/3/497/23959780/znu00905000497.pdf

J. M. Cevallos-cevallos, J. I. Reyes-de-corcuera, E. Etxeberria, M. D. Danyluk, and G. E. Rodrick, Metabolomic analysis in food science: a review, Trends Food Sci Tech, vol.20, issue.11, pp.557-66, 2009.

A. Cifuentes, Food analysis and foodomics, J Chromatogr A, vol.1216, issue.43, p.7109, 2009.
DOI : 10.1016/j.chroma.2009.09.018

URL : https://hal.archives-ouvertes.fr/hal-01564474

F. S. Collins and H. Varmus, A new initiative on precision medicine, N Engl J Med, vol.372, issue.9, pp.793-798, 2015.
DOI : 10.1056/nejmp1500523

URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5101938/pdf

F. Biomedical, NIH definition of biomarker, Clin Pharmacol Ther, vol.69, pp.89-95, 2001.

L. H. Epstein, The direct effects of compliance on health outcome, Health Psychology, vol.3, issue.4, p.385, 1984.

W. B. Dunn, D. Broadhurst, P. Begley, E. Zelena, S. Francis-mcintyre et al., Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry, Nat Protoc, vol.6, issue.7, pp.1060-83, 2011.

Z. Pan and D. Raftery, Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics, Analytical and bioanalytical chemistry, vol.387, issue.2, pp.525-532, 2007.
DOI : 10.1007/s00216-006-0687-8

J. K. Nicholson, J. C. Lindon, and E. Holmes, Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data, Xenobiotica, vol.29, issue.11, pp.1181-1190, 1999.

O. Fiehn, Metabolomics--the link between genotypes and phenotypes, Plant Mol Biol, vol.48, issue.1-2, pp.155-71, 2002.
DOI : 10.1007/978-94-010-0448-0_11

K. Dettmer and B. D. Hammock, Metabolomics--a new exciting field within the" omics" sciences. Environ Health Persp, vol.112, p.396, 2004.
DOI : 10.1289/ehp.112-1241997

URL : https://ehp.niehs.nih.gov/doi/pdf/10.1289/ehp.112-1241997

E. J. Want, I. D. Wilson, H. Gika, G. Theodoridis, R. S. Plumb et al., Global metabolic profiling procedures for urine using UPLC-MS, Nat Protoc, vol.5, issue.6, pp.1005-1023, 2010.
DOI : 10.1038/nprot.2010.50

O. Beckonert, H. C. Keun, T. M. Ebbels, J. Bundy, E. Holmes et al., Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts, Nat Protoc, vol.2, issue.11, pp.2692-703, 2007.

W. B. Dunn, I. D. Wilson, A. W. Nicholls, and D. Broadhurst, The importance of experimental design and QC samples in large-scale and MS-driven untargeted metabolomic studies of humans, Bioanalysis, vol.4, issue.18, pp.2249-64, 2012.

, Design and analysis of experiments with high throughput biological assay data, Seminars in cell & developmental biology, 2004.

, Metabolomics: Current analytical platforms and methodologies, TrAC Trends in Analytical Chemistry, vol.24, issue.4, pp.285-94, 2005.

B. D. Sykes, Urine stability for metabolomic studies: effects of preparation and storage, Metabolomics, vol.3, issue.1, pp.19-27, 2007.

M. A. Fernández-peralbo, L. De-castro, and M. D. , Preparation of urine samples prior to targeted or untargeted metabolomics mass-spectrometry analysis, TrAC Trends in Analytical Chemistry, vol.41, pp.75-85, 2012.

P. Yin, A. Peter, H. Franken, X. Zhao, S. S. Neukamm et al., Preanalytical aspects and sample quality assessment in metabolomics studies of human blood, Clin Chem, vol.59, issue.5, pp.833-878, 2013.

E. R. Andrew, Nuclear magnetic resonance. Nuclear Magnetic Resonance, vol.1, 2009.

J. A. Koutcher and C. T. Burt, Principles of nuclear magnetic resonance, J Nucl Med, vol.25, issue.1, pp.101-112, 1984.

E. D. Becker, High resolution NMR: theory and chemical applications, 1999.

R. G. Brewer and R. Shoemaker, Optical free induction decay, Physical Review A, vol.6, issue.6, 1972.
DOI : 10.1103/physreva.6.2001

H. Yamamoto, K. Saitoh, H. Hasegawa, and H. Ochi, NMR spectrometer and NMR probe, Google Patents

M. Defernez and I. J. Colquhoun, Factors affecting the robustness of metabolite fingerprinting using 1H NMR spectra, Phytochemistry, vol.62, issue.6, pp.1009-1026, 2003.

A. Shimizu, M. Ikeguchi, S. Sugai, . Appropriateness, . Tsp et al., J Biomol NMR, vol.4, issue.6, pp.859-62, 1994.

J. Vandegans and A. De-kersabiec, Spectrométrie d'absorption atomique

E. Hoffmann, Mass spectrometry. Wiley Online Library, 1996.

M. S. Munson and F. Field, Chemical ionization mass spectrometry. I. General introduction, J Am Chem Soc, vol.88, issue.12, pp.2621-2651, 1966.

M. Barber, R. S. Bordoli, R. D. Sedgwick, and A. N. Tyler, Fast atom bombardment of solids (FAB): A new ion source for mass spectrometry, Journal of the Chemical Society, Chemical Communications, issue.7, pp.325-332, 1981.

F. J. Andrade, J. T. Shelley, W. C. Wetzel, M. R. Webb, G. Gamez et al., Atmospheric pressure chemical ionization source. 1. Ionization of compounds in the gas phase, Anal Chem, vol.80, issue.8, pp.2646-53, 2008.

F. Hillenkamp, M. Karas, R. C. Beavis, and B. T. Chait, Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers, Anal Chem, vol.63, issue.24, pp.1193-203, 1991.

P. Dawson, Quadrupole mass analyzers: performance, design and some recent applications, Mass Spectrom Rev, vol.5, issue.1, pp.1-37, 1986.

M. Balcerzak, An overview of analytical applications of time of flight-mass spectrometric

, analyzers and an inductively coupled plasma-TOF-MS technique, Anal Sci, vol.19, issue.7, pp.979-89, 2003.

A. Makarov, E. Denisov, A. Kholomeev, W. Balschun, O. Lange et al., Performance evaluation of a hybrid linear ion trap/orbitrap mass spectrometer, Anal Chem, vol.78, issue.7, pp.2113-2133, 2006.

Q. Hu, R. J. Noll, H. Li, A. Makarov, M. Hardman et al., The Orbitrap: a new mass spectrometer, J Mass Spectrom, vol.40, issue.4, pp.430-473, 2005.

A. G. Marshall, C. L. Hendrickson, and G. S. Jackson, Fourier transform ion cyclotron resonance mass spectrometry: a primer, Mass Spectrom Rev, vol.17, issue.1, pp.1-35, 1998.

S. A. Mcluckey, G. L. Glish, V. Berkel, and G. J. , Charge determination of product ions formed from collisioninduced dissociation of multiply protonated molecules via ion/molecule reactions, Anal Chem, vol.63, issue.18, pp.1971-1979, 1991.

Q. Hu, R. J. Noll, H. Li, A. Makarov, M. Hardman et al., The Orbitrap: a new mass spectrometer, J Mass Spectrom, vol.40, issue.4, pp.430-473, 2005.

S. Bachmann, A. Bressan, L. Ropelewski, F. Sauli, A. Sharma et al., Charge amplification and transfer processes in the gas electron multiplier. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, vol.438, pp.376-408, 1999.

R. Patel, M. Roy, and G. Dutta, Mass spectrometry-A review, Veterinary World, vol.5, issue.3, pp.185-92, 2012.

F. W. Mclafferty, Tandem mass spectrometry, Science, vol.214, issue.4518, pp.280-287, 1981.

J. C. Giddings, Dynamics of chromatography: principles and theory, 2002.

R. Smith, J. Haken, and M. Wainwright, Evaluation of mathematical procedures for the calculation of deadtime, J Chromatogr A, vol.147, pp.65-73, 1978.

W. W. Christie, Gas chromatography and lipids, 1989.

J. R. Cooper, I. C. Bowater, and C. L. Wilkins, Gas chromatography/Fourier transform infrared/mass spectrometry using a mass selective detector, Anal Chem, vol.58, issue.13, pp.2791-2797, 1986.
DOI : 10.1021/ac00126a046

D. R. Knapp, Handbook of analytical derivatization reactions, 1979.

M. Petrovic and D. Barcelo, Liquid chromatography-tandem mass spectrometry, Analytical and bioanalytical chemistry, vol.405, issue.18, pp.5857-5865, 2013.

R. E. Majors and M. Przybyciel, Columns for reversed-phase LC separations in highly aqueous mobile phases, Lc Gc N Am, vol.20, issue.7, pp.584-93, 2002.

S. Cubbon, C. Antonio, J. Wilson, and J. Thomas-oates, Metabolomic applications of hilic-lc-ms, Mass Spectrom Rev, vol.29, issue.5, pp.671-84, 2010.
DOI : 10.1002/mas.20252

M. E. Swartz, UPLC?: an introduction and review, J Liq Chromatogr R T, vol.28, issue.7-8, pp.1253-63, 2005.
DOI : 10.1081/jlc-200053046

R. Ramautar, G. W. Somsen, and G. J. De-jong, CE-MS in metabolomics, Electrophoresis, vol.30, issue.1, pp.276-91, 2009.

R. Ramautar, O. A. Mayboroda, G. W. Somsen, and G. J. De-jong, CE-MS for metabolomics: Developments and applications in the period, Electrophoresis, vol.32, issue.1, pp.52-65, 2008.

A. Shevchenko and K. Simons, Lipidomics: coming to grips with lipid diversity, Nat Rev Mol Cell Bio
DOI : 10.1038/nrm2934

J. Hochrein, H. U. Zacharias, F. Taruttis, C. Samol, J. C. Engelmann et al., Data Normalization

H. Nmr-metabolite, Fingerprinting Data Sets in the Presence of Unbalanced Metabolite Regulation, J Proteome Res, vol.14, issue.8, pp.3217-3245, 2015.

F. Dieterle, A. Ross, G. Schlotterbeck, and H. Senn, Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in H-1 NMR metabonomics, Anal Chem, vol.78, issue.13, pp.4281-90, 2006.

J. Lee, J. Park, M. S. Lim, S. J. Seong, J. J. Seo et al., Quantile Normalization Approach for Liquid Chromatography-Mass Spectrometry-based Metabolomic Data from Healthy Human Volunteers, Anal Sci, vol.28, issue.8, pp.801-806, 2012.

S. Gallon, J. M. Loubes, and E. Maza, Statistical properties of the quantile normalization method for density curve alignment, Math Biosci, vol.242, issue.2, pp.129-171, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00593476

R. A. Van-den-berg, H. C. Hoefsloot, J. A. Westerhuis, A. K. Smilde, and M. J. Van-der-werf, Centering, scaling, and transformations: improving the biological information content of metabolomics data, BMC genomics, vol.7, p.142, 2006.

D. Meyer, T. Sinnaeve, D. Van-gasse, B. Rietzschel, E. R. et al., Evaluation of standard and advanced preprocessing methods for the univariate analysis of blood serum H-1-NMR spectra, Analytical and Bioanalytical Chemistry, vol.398, issue.4, pp.1781-90, 2010.

J. D. Gibbons and S. Chakraborti, Nonparametric statistical inference, 2011.

U. Kaempf, The binomial test: a simple tool to identify process problems

M. J. Norusis, SPSS: Statistical data analysis. SPSS, 1990.

R. G. Miller, Beyond ANOVA: basics of applied statistics, 1997.

V. Estivill-castro, Why so many clustering algorithms: a position paper, ACM SIGKDD explorations newsletter, vol.4, issue.1, pp.65-75, 2002.

C. C. Bridges, Hierarchical cluster analysis, Psychological reports, vol.18, issue.3, pp.851-855, 1966.

A. Saghatelian, S. A. Trauger, E. J. Want, E. G. Hawkins, G. Siuzdak et al., Assignment of endogenous substrates to enzymes by global metabolite profiling, Biochemistry, vol.43, issue.45, pp.14332-14341, 2004.

I. Jolliffe, Principal component analysis. Wiley Online Library, 2002.

S. Wold, K. Esbensen, and P. Geladi, Principal component analysis, Chemometr Intell Lab, vol.2, issue.1-3, pp.37-52, 1987.

H. Abdi and L. J. Williams, Principal component analysis, Wiley Interdisciplinary Reviews: Computational Statistics, vol.2, issue.4, pp.433-59, 2010.
DOI : 10.1002/wics.101

URL : https://hal.archives-ouvertes.fr/hal-01259094

S. Wold, M. Sjöström, and L. Eriksson, PLS-regression: a basic tool of chemometrics, Chemometr Intell Lab, vol.58, issue.2, pp.109-139, 2001.

M. Bylesjö, M. Rantalainen, O. Cloarec, J. K. Nicholson, E. Holmes et al., OPLS discriminant analysis: combining the strengths of PLS-DA and SIMCA classification, J Chemometr, vol.20, issue.8-10, pp.341-51, 2006.

B. Worley and R. Powers, Multivariate analysis in metabolomics, Current Metabolomics, vol.1, issue.1, pp.92-107, 2013.
DOI : 10.2174/2213235x130108

URL : https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1034&context=chemistrypowers

B. Lu, I. Castillo, L. Chiang, and T. F. Edgar, Industrial PLS model variable selection using moving window variable importance in projection, Chemometr Intell Lab, vol.135, pp.90-109, 2014.
DOI : 10.1016/j.chemolab.2014.03.020

V. Bewick, L. Cheek, and J. Ball, Statistics review 13: Receiver operating characteristic curves, Critical Care, vol.8, issue.6, p.508, 2004.

J. A. Westerhuis, E. J. Van-velzen, H. C. Hoefsloot, and A. K. Smilde, Multivariate paired data analysis: multilevel PLSDA versus OPLSDA, Metabolomics, 2010.
DOI : 10.1007/s11306-009-0185-z

URL : https://link.springer.com/content/pdf/10.1007%2Fs11306-009-0185-z.pdf

S. Bijlsma, I. Bobeldijk, E. R. Verheij, R. Ramaker, S. Kochhar et al., Large-scale human metabolomics studies: a strategy for data (pre-) processing and validation, Anal Chem, vol.78, issue.2, pp.567-74, 2006.
DOI : 10.1021/ac051495j

N. J. Serkova and C. U. Niemann, Pattern recognition and biomarker validation using quantitative 1H-NMRbased metabolomics. Expert review of molecular diagnostics, vol.6, pp.717-748, 2006.
DOI : 10.1586/14737159.6.5.717

M. N. Triba, L. Moyec, L. Amathieu, R. Goossens, C. Bouchemal et al., PLS/OPLS models in metabolomics: the impact of permutation of dataset rows on the K-fold cross-validation quality parameters. Molecular bioSystems, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01251268

J. A. Westerhuis, H. Hoefsloot, S. Smit, D. J. Vis, A. K. Smilde et al., Assessment of PLSDA cross validation, Metabolomics, 2008.

F. Lindgren, B. Hansen, W. Karcher, M. Sjöström, and L. Eriksson, Model validation by permutation tests: Applications to variable selection, J Chemometr, vol.10, issue.5-6, pp.521-553, 1996.
DOI : 10.1002/(sici)1099-128x(199609)10:5/6<521::aid-cem448>3.3.co;2-a

C. Ke, A. Li, Y. Hou, M. Sun, K. Yang et al., Metabolic phenotyping for monitoring ovarian cancer patients, Scientific reports, vol.6, 2016.
DOI : 10.1038/srep23334

URL : https://www.nature.com/articles/srep23334.pdf

J. A. Hanley and B. J. Mcneil, The meaning and use of the area under a receiver operating characteristic (ROC) curve, Radiology, vol.143, issue.1, pp.29-36, 1982.

M. Kanehisa, M. Araki, S. Goto, M. Hattori, M. Hirakawa et al., KEGG for linking genomes to life and the environment, Nucleic Acids Res, vol.36, issue.1, pp.480-484, 2008.

M. Kanehisa, S. Goto, M. Hattori, K. F. Aoki-kinoshita, M. Itoh et al., From genomics to chemical genomics: new developments in KEGG, Nucleic Acids Res, vol.34, issue.1, pp.354-361, 2006.

D. S. Wishart, D. Tzur, C. Knox, R. Eisner, A. C. Guo et al., HMDB: the human metabolome database, Nucleic Acids Res, vol.35, issue.1, pp.521-527, 2007.
URL : https://hal.archives-ouvertes.fr/hal-01712873

J. Xia, I. V. Sinelnikov, B. Han, and D. S. Wishart, MetaboAnalyst 3.0-making metabolomics more meaningful, Nucleic Acids Res, vol.43, issue.W1, pp.251-258, 2015.
DOI : 10.1093/nar/gkv380

URL : https://academic.oup.com/nar/article-pdf/43/W1/W251/17435854/gkv380.pdf

P. D. Karp, C. A. Ouzounis, C. Moore-kochlacs, L. Goldovsky, P. Kaipa et al., Expansion of the BioCyc collection of pathway/genome databases to 160 genomes, Nucleic Acids Res, vol.33, pp.6083-6092, 2005.

L. Puchades-carrasco, M. Palomino-schatzlein, C. Perez-rambla, and A. Pineda-lucena, Bioinformatics tools for the analysis of NMR metabolomics studies focused on the identification of clinically relevant biomarkers, Briefings in bioinformatics, vol.17, issue.3, pp.541-52, 2016.

Z. Pan and D. Raftery, Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics, Analytical and bioanalytical chemistry, vol.387, issue.2, pp.525-532, 2007.

P. J. Foxall, M. Spraul, R. D. Farrant, L. C. Lindon, G. H. Neild et al., 750 MHz 1H-NMR spectroscopy of human blood plasma, J Pharm Biomed Anal, vol.11, issue.4-5, pp.267-76, 1993.

N. Schauer, D. Steinhauser, S. Strelkov, D. Schomburg, G. Allison et al., GC-MS libraries for the rapid identification of metabolites in complex biological samples, Febs Lett, vol.579, issue.6, pp.1332-1339, 2005.

G. Theodoridis, H. G. Gika, and W. Id, LC-MS-based methodology for global metabolite profiling in metabonomics/metabolomics, TrAC Trends in Analytical Chemistry, vol.27, issue.3, pp.251-60, 2008.

D. J. Crockford, E. Holmes, J. C. Lindon, R. S. Plumb, S. Zirah et al., Statistical heterospectroscopy, an approach to the integrated analysis of NMR and UPLC-MS data sets: application in metabonomic toxicology studies, Anal Chem, vol.78, issue.2, pp.363-71, 2006.

D. J. Crockford, A. D. Maher, K. R. Ahmadi, A. Barrett, R. S. Plumb et al., 1H NMR and UPLC-MSE statistical heterospectroscopy: characterization of drug metabolites (xenometabolome) in epidemiological studies, Anal Chem, vol.80, issue.18, pp.6835-6879, 2008.

H. Wu, A. D. Southam, A. Hines, and M. R. Viant, High-throughput tissue extraction protocol for NMR-and MS-based metabolomics, Anal Biochem, vol.372, issue.2, pp.204-216, 2008.

K. Bingol, L. Bruschweiler-li, C. Yu, A. Somogyi, F. Zhang et al., Metabolomics beyond spectroscopic databases: a combined MS/NMR strategy for the rapid identification of new metabolites in complex mixtures, Anal Chem, vol.87, issue.7, pp.3864-70, 2015.

R. C. Bone, R. A. Balk, F. B. Cerra, R. P. Dellinger, A. M. Fein et al., Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis, Chest, vol.101, issue.6, pp.1644-55, 1992.

R. P. Dellinger, M. M. Levy, A. Rhodes, D. Annane, H. Gerlach et al., Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, Intens Care Med, vol.39, issue.2, pp.165-228, 2012.

R. L. Dellinger, . Mm-;-carlet, J. Jm-;-bion, . Parker, R. Mm-;-jaeschke et al.,

. Angus, C. Dc;-brunbuisson, R. Beale, and . Surviving-sepsis-campaign, International guidelines for management of severe sepsis and septic shock, CRITICAL CARE MEDICINE, vol.36, pp.296-327, 2008.

R. A. Balk, Systemic inflammatory response syndrome (SIRS): where did it come from and is it still relevant today?, Virulence, vol.5, issue.1, pp.20-26, 2014.
DOI : 10.4161/viru.27135

URL : http://europepmc.org/articles/pmc3916374?pdf=render

I. Martin-loeches, M. M. Levy, and A. Artigas, Management of severe sepsis: advances, challenges, and current status. Drug design, development and therapy, vol.9, pp.2079-88, 2015.

M. Singer, D. Santis, V. Vitale, D. Jeffcoate, and W. , Multiorgan failure is an adaptive, endocrine-mediated, metabolic response to overwhelming systemic inflammation, The Lancet, vol.364, issue.9433, pp.545-553, 2004.

D. C. Angus and T. Van-der-poll, Severe sepsis and septic shock, N Engl J Med, vol.369, issue.9, pp.840-51, 2013.

Z. Cao and R. A. Robinson, The role of proteomics in understanding biological mechanisms of sepsis

, Proteomics Clin Appl, vol.8, issue.1-2, pp.35-52, 2014.

N. Haase, J. Wetterslev, P. Winkel, and A. Perner, Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial, Intensive care medicine, vol.39, issue.12, pp.2126-2160, 2013.

N. Semeraro, C. T. Ammollo, F. Semeraro, and M. Colucci, Sepsis, thrombosis and organ dysfunction
DOI : 10.1016/j.thromres.2011.10.013

, Thromb Res, vol.129, issue.3, pp.290-295, 2012.

C. M. Tsao, S. T. Ho, and C. C. Wu, Coagulation abnormalities in sepsis, Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists, vol.53, issue.1, pp.16-22, 2015.
DOI : 10.1016/j.aat.2014.11.002

URL : https://doi.org/10.1016/j.aat.2014.11.002

D. T. Janigan, M. J. , H. D. Acute, N. Fat, . Subcutaneous et al., Am J Kidney Dis

E. Jean-baptiste, Cellular mechanisms in sepsis, J Intensive Care Med, vol.22, issue.2, pp.63-72, 2007.
DOI : 10.1177/0885066606297123

G. Ramachandran, Gram-positive and gram-negative bacterial toxins in sepsis: a brief review
DOI : 10.4161/viru.27024

URL : http://europepmc.org/articles/pmc3916377?pdf=render

, Virulence, vol.5, issue.1, pp.213-221, 2014.

R. Ferrer, I. Martin-loeches, G. Phillips, T. M. Osborn, S. Townsend et al., Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program, Critical care medicine, vol.42, issue.8, pp.1749-55, 2014.

M. P. Emanuel-rivers-md, . Bryant, M. D. Nguyen, A. Suzanneh, M. A. Ulierssler et al., EARLY GOAL-DIRECTED THERAPY IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCK, The New England Journal of Medicine, vol.345, pp.1368-77, 2001.

A. L. Shane and B. J. Stoll, Neonatal sepsis: progress towards improved outcomes, J Infect, vol.68, issue.1, pp.24-32, 2014.
DOI : 10.1016/j.jinf.2013.09.011

K. A. Wichterman, A. E. Baue, and I. H. Chaudry, SEPSIS AND SEPTIC SHOCK -A REVIEW OF LABORATORY MODELS AND A PROPOSAL, J Surg Res, vol.29, issue.2, pp.189-201, 1980.

X. Zhao, Y. X. Chen, and C. S. Li, Predictive value of the complement system for sepsis-induced disseminated intravascular coagulation in septic patients in emergency department, J Crit Care, vol.30, issue.2, pp.290-295, 2015.

S. Y. Cho and J. H. Choi, Biomarkers of sepsis, Infect Chemother, vol.46, issue.1, pp.1-12, 2014.

C. Henriquez-camacho and J. Losa, Biomarkers for sepsis, Biomed Res Int, p.547818, 2014.

M. J. Sweet and D. A. Hume, Endotoxin signal transduction in macrophages, J Leukocyte Biol, vol.60, issue.1, pp.8-26, 1996.
DOI : 10.1002/jlb.60.1.8

D. H. Yu, D. H. Nho, R. H. Song, S. H. Kim, M. J. Lee et al., High-mobility group box 1 as a surrogate prognostic marker in dogs with systemic inflammatory response syndrome, J Vet Emerg Crit Care, vol.20, issue.3, pp.298-302, 2010.

R. L. Kitchens and P. A. Thompson, Impact of sepsis-induced changes in plasma on LPS interactions with monocytes and plasma lipoproteins: roles of soluble CD14, LBP, and acute phase lipoproteins, J Endotoxin Res, vol.9, issue.2, pp.113-121, 2003.

C. W. Frevert, G. Matute-bello, S. J. Skerrett, R. B. Goodman, O. Kajikawa et al., Effect of CD14 Blockade in Rabbits with Escherichia coli Pneumonia and Sepsis, The Journal of Immunology, vol.164, issue.10, pp.5439-5484, 2000.

B. Clyne and J. S. Olshaker, The C-reactive protein, J Emerg Med, vol.17, issue.6, pp.1019-1044, 1999.

E. Louis, D. Franchimont, A. Piron, Y. Gevaert, N. Schaaf-lafontaine et al., Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans, Clin Exp Immunol, vol.113, issue.3, pp.401-407, 1998.

T. Yoshimura, K. Matsushima, J. J. Oppenheim, and E. J. Leonard, NEUTROPHIL CHEMOTACTIC FACTOR PRODUCED BY LIPOPOLYSACCHARIDE (LPS)-STIMULATED HUMAN-BLOOD MONONUCLEAR LEUKOCYTES -PARTIAL CHARACTERIZATION AND SEPARATION FROM INTERLEUKIN-1 (IL-1), J Immunol, vol.139, issue.3, pp.788-93, 1987.

D. J. Berg, R. Kuhn, K. Rajewsky, W. Muller, S. Menon et al., INTERLEUKIN-10 IS A CENTRAL REGULATOR OF THE RESPONSE TO LPS IN MURINE MODELS OF ENDOTOXIC-SHOCK AND THE SHWARTZMAN REACTION BUT NOT ENDOTOXIN TOLERANCE, J Clin Invest, vol.96, issue.5, pp.2339-2386, 1995.

V. Hoerr, L. Zbytnuik, C. Leger, P. P. Tam, P. Kubes et al., Gram-negative and Gram-positive bacterial infections give rise to a different metabolic response in a mouse model, Journal of proteome research, vol.11, issue.6, pp.3231-3276, 2012.

L. Su, Y. Huang, Y. Zhu, L. Xia, R. Wang et al., Discrimination of sepsis stage metabolic profiles with an LC/MS-MS-based metabolomics approach, BMJ open respiratory research, vol.1, issue.1, p.56, 2014.

J. L. Izquierdo-garcia, N. Nin, J. Ruiz-cabello, Y. Rojas, M. De-paula et al., A metabolomic approach for diagnosis of experimental sepsis, Intensive Care Med, vol.37, issue.12, pp.2023-2055, 2011.

B. Mickiewicz, H. J. Vogel, H. R. Wong, and B. W. Winston, Metabolomics as a novel approach for early diagnosis of pediatric septic shock and its mortality, Am J Respir Crit Care Med, vol.187, issue.9, pp.967-76, 2013.

V. Fanos, P. Caboni, G. Corsello, M. Stronati, D. Gazzolo et al., Urinary 1 H-NMR and GC-MS metabolomics predicts early and late onset neonatal sepsis, Early human development, vol.90, pp.78-83, 2014.
DOI : 10.1016/s0378-3782(14)70024-6

URL : https://iris.unipa.it/bitstream/10447/96399/1/Early%20Human%20Development%202014.pdf

D. Schmerler, S. Neugebauer, K. Ludewig, S. Bremer-streck, F. M. Brunkhorst et al., Targeted metabolomics for discrimination of systemic inflammatory disorders in critically ill patients, Journal of lipid research, 2012.

W. J. Hubbard, M. Choudhry, M. G. Schwacha, J. D. Kerby, I. Rue et al., Cecal ligation and puncture. Shock, vol.24, pp.52-59, 2005.

Z. Y. Lin, P. B. Xu, S. K. Yan, H. B. Meng, G. J. Yang et al., A metabonomic approach to early prognostic evaluation of experimental sepsis by (1)H NMR and pattern recognition, Nmr Biomed, vol.22, issue.6, pp.601-609, 2009.

P. B. Xu, Z. Y. Lin, H. B. Meng, S. K. Yan, Y. Yang et al., A metabonomic approach to early prognostic evaluation of experimental sepsis, J Infect, vol.56, issue.6, pp.474-81, 2008.

M. Garcia-simon, J. M. Morales, V. Modesto-alapont, V. Gonzalez-marrachelli, R. Vento-rehues et al., Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1 H NMR Urine Metabolomics in the Intensive Care Unit, PloS one, vol.10, issue.11, p.140993, 2015.

B. Mickiewicz, P. Tam, C. N. Jenne, C. Leger, J. Wong et al., Integration of metabolic and inflammatory mediator profiles as a potential prognostic approach for septic shock in the intensive care unit, Crit Care, vol.19, p.11, 2015.

R. J. Langley, E. L. Tsalik, J. C. Van-velkinburgh, S. W. Glickman, B. J. Rice et al., An integrated clinicometabolomic model improves prediction of death in sepsis, Science translational medicine, vol.5, pp.195-95, 0195.

H. E. Wasmuth, D. Kunz, E. Yagmur, A. Timmer-stranghoner, D. Vidacek et al., Patients with acute on chronic liver failure display "sepsis-like" immune paralysis, J Hepatol, vol.42, issue.2, pp.195-201, 2005.

E. Abraham and M. Singer, Mechanisms of sepsis-induced organ dysfunction. Critical care medicine, vol.35, pp.2408-2424, 2007.

R. W. Schrier and W. Wang, Acute renal failure and sepsis, New Engl J Med, vol.351, issue.2, pp.159-69, 2004.

M. Vincent, Consensus conference definitions for sepsis, septic shock, acute lung injury, and acute respiratory distress syndrome: time for a reevaluation, Critical care medicine, vol.28, issue.1, pp.232-237, 2000.

D. Hasper, M. Hummel, F. Kleber, I. Reindl, and H. Volk, Systemic inflammation in patients with heart failure, Eur Heart J, vol.19, issue.5, pp.761-766, 1998.

D. J. Marquardt, N. L. Knatz, L. A. Wetterau, M. D. Wewers, and M. W. Hall, Failure to recover somatotropic axis function is associated with mortality from pediatric sepsis-induced multiple organ dysfunction syndrome. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, vol.11, pp.18-25, 2010.

K. A. Stringer and N. , , vol.2

. Standiford, Metabolic consequences of sepsis-induced acute lung injury revealed by plasma 1H-nuclear magnetic resonance quantitative metabolomics and computational analysis, AJP-Lung Cell Mol Physiol, vol.300, pp.4-11, 2011.

P. Recknagel, F. A. Gonnert, M. Westermann, S. Lambeck, A. Lupp et al., Liver dysfunction and phosphatidylinositol-3-kinase signalling in early sepsis: experimental studies in rodent models of peritonitis, PLoS medicine, vol.9, issue.11, p.1001338, 2012.

Y. Liu, S. Yan, C. Ji, W. Dai, W. Hu et al., Metabolomic changes and protective effect of (L)-carnitine in rat kidney ischemia/reperfusion injury, Kidney Blood Press Res, vol.35, issue.5, pp.373-81, 2012.

J. Hinkelbein, A. Kalenka, C. Schubert, A. Peterka, J. Feldmann et al., Proteome and metabolome alterations in heart and liver indicate compromised energy production during sepsis, Protein Peptide Lett, vol.17, issue.1, pp.18-31, 2010.

K. A. Stringer, J. G. Younger, C. Mchugh, L. Yeomans, M. A. Finkel et al., Whole Blood Reveals More Metabolic Detail of the Human Metabolome Than Serum as Measured by 1H-NMR Spectroscopy: Implications for Sepsis Metabolomics, 2015.

Z. Cao, S. Yende, J. A. Kellum, D. C. Angus, and R. A. Robinson, Proteomics reveals age-related differences in the host immune response to sepsis, Journal of proteome research, vol.13, issue.2, pp.422-454, 2014.

W. Wu and S. Zhao, Metabolic changes in cancer: beyond the Warburg effect, Acta Bioch Bioph Sin, vol.45, issue.1, pp.18-26, 2013.

J. A. Leithead, P. C. Hayes, and J. W. Ferguson, Review article: advances in the management of patients with cirrhosis and portal hypertension-related renal dysfunction, Aliment Pharmacol Ther, vol.39, issue.7, pp.699-711, 2014.

B. Sauneuf, B. Champigneulle, A. Soummer, N. Mongardon, J. Charpentier et al., Increased survival of cirrhotic patients with septic shock, Crit Care, vol.17, issue.2, p.10, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00873495

A. S. Go, G. M. Chertow, D. Fan, C. E. Mcculloch, and C. Hsu, Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization, New Engl J Med, vol.351, issue.13, pp.1296-305, 2004.

A. Zhang, H. Sun, and X. Wang, Serum metabolomics as a novel diagnostic approach for disease: a systematic review, Analytical and bioanalytical chemistry, vol.404, issue.4, pp.1239-1284, 2012.

J. M. Llovet, A. Burroughs, and J. Bruix, Hepatocellular carcinoma. The Lancet, vol.362, pp.1907-1924, 2003.
URL : https://hal.archives-ouvertes.fr/hal-01910322

S. O&apos;connor, J. Ward, M. Watson, B. Momin, and L. Richardson, Hepatocellular carcinoma-United States, Morbidity and Mortality Weekly Report, vol.59, issue.17, pp.517-537, 2001.

H. B. El-serag, Epidemiology of viral hepatitis and hepatocellular carcinoma, Gastroenterology, vol.142, issue.6, pp.1264-73, 2012.

F. Donato, A. Tagger, U. Gelatti, G. Parrinello, P. Boffetta et al., Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women, American journal of epidemiology, vol.155, issue.4, pp.323-354, 2002.

M. C. Kew, Aflatoxins as a cause of hepatocellular carcinoma, J Gastrointestin Liver Dis, vol.22, issue.3, pp.305-315, 2013.

J. M. Page, S. A. Harrison, and H. Nash, Clinics in liver disease, vol.13, issue.4, pp.631-678, 2009.

Z. M. Younossi, M. Otgonsuren, L. Henry, C. Venkatesan, A. Mishra et al., Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from, Hepatology, vol.62, issue.6, pp.1723-1753, 2004.

E. S. Bialecki, D. Bisceglie, and A. M. , Diagnosis of hepatocellular carcinoma. HPB : the official journal of the International Hepato Pancreato Biliary Association, vol.7, pp.26-34, 2005.

F. Pons, M. Varela, and J. M. Llovet, Staging systems in hepatocellular carcinoma. HPB : the official journal of the International Hepato Pancreato Biliary Association, vol.7, pp.35-41, 2005.

R. H. Wiesner, R. B. Freeman, and D. C. Mulligan, Liver transplantation for hepatocellular cancer: the impact of the MELD allocation policy, Gastroenterology, vol.127, issue.5, pp.261-268, 2004.

R. Hu, P. Lee, Y. Dai, H. Sheu, J. Lai et al., Surgical resection for recurrent hepatocellular carcinoma: prognosis and analysis of risk factors, Surgery, vol.120, issue.1, pp.23-32, 1996.

S. Lin, C. Lin, C. Lin, C. Hsu, and Y. Chen, Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less, Gut, vol.54, issue.8, pp.1151-1157, 2005.

T. Livraghi, L. Solbiati, M. F. Meloni, G. S. Gazelle, E. F. Halpern et al., Treatment of focal liver tumors with percutaneous radio-frequency ablation: Complications encountered in a multicenter study 1, Radiology, vol.226, issue.2, pp.441-51, 2003.

T. Livraghi, S. N. Goldberg, S. Lazzaroni, F. Meloni, L. Solbiati et al., Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection, Radiology, vol.210, issue.3, pp.655-61, 1999.

R. W. Johnstone, A. A. Ruefli, and S. W. Lowe, Apoptosis: a link between cancer genetics and chemotherapy, Cell, vol.108, issue.2, pp.153-64, 2002.

S. F. Altekruse, K. A. Mcglynn, and M. E. Reichman, Hepatocellular Carcinoma Incidence, Mortality, and Survival Trends in the United States From 1975 to, J Clin Oncol, vol.27, issue.9, pp.1485-91, 2005.

A. Forner, R. Vilana, C. Ayuso, L. Bianchi, M. Solé et al., Diagnosis of hepatic nodules 20 mm or smaller in cirrhosis: prospective validation of the noninvasive diagnostic criteria for hepatocellular carcinoma, Hepatology, vol.47, issue.1, pp.97-104, 2008.

Y. Tan, P. Yin, L. Tang, W. Xing, Q. Huang et al., Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis, Molecular & cellular proteomics : MCP, vol.11, issue.2, pp.111-010694, 2012.

Y. Liu, Z. Hong, G. Tan, X. Dong, G. Yang et al., NMR and LC/MS-based global metabolomics to identify serum biomarkers differentiating hepatocellular carcinoma from liver cirrhosis, Int J Cancer, vol.135, issue.3, pp.658-68, 2014.
DOI : 10.1002/ijc.28706

A. Fages, T. Duarte-salles, M. Stepien, P. Ferrari, V. Fedirko et al., Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort, BMC medicine, vol.13, p.242, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01234339

L. Zhou, Q. Wang, P. Yin, W. Xing, Z. Wu et al., Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases, Analytical and bioanalytical chemistry, vol.403, issue.1, pp.203-216, 2012.

P. Nahon, R. Amathieu, M. N. Triba, N. Bouchemal, J. C. Nault et al., Identification of serum proton NMR metabolomic fingerprints associated with hepatocellular carcinoma in patients with alcoholic cirrhosis, Clin Cancer Res, vol.18, issue.24, pp.6714-6736, 2012.

T. Chen, G. Xie, X. Wang, J. Fan, Y. Qiu et al., Serum and Urine Metabolite Profiling Reveals Potential Biomarkers of Human Hepatocellular Carcinoma, Molecular & Cellular Proteomics, vol.10, issue.7, 2011.

Q. Huang, Y. Tan, P. Yin, G. Ye, P. Gao et al., Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics, Cancer Res, vol.73, issue.16, pp.4992-5002, 2013.

G. Ye, B. Zhu, Z. Yao, P. Yin, X. Lu et al., Analysis of urinary metabolic signatures of early hepatocellular carcinoma recurrence after surgical removal using gas chromatography-mass spectrometry, Journal of proteome research, vol.11, issue.8, pp.4361-72, 2012.

L. Zhou, Y. Liao, P. Yin, Z. Zeng, J. Li et al., Metabolic profiling study of early and late recurrence of hepatocellular carcinoma based on liquid chromatography-mass spectrometry, J Chromatogr B Analyt Technol Biomed Life Sci, vol.966, pp.163-70, 2014.

J. Wang, S. Zhang, Z. Li, J. Yang, C. Huang et al., )H-NMR-based metabolomics of tumor tissue for the metabolic characterization of rat hepatocellular carcinoma formation and metastasis, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, vol.32, issue.1, pp.223-254, 2011.

S. Takano, O. Yokosuka, F. Imazeki, M. Tagawa, M. Omata et al., CHRONIC HEPATITIS-B AND HEPATITIS-C -A PROSPECTIVE-STUDY OF 251 PATIENTS

, Hepatology, vol.21, issue.3, pp.650-655, 1995.

J. F. Perz, G. L. Armstrong, L. A. Farrington, Y. J. Hutin, and B. P. Bell, The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide, J Hepatol, vol.45, issue.4, pp.529-567, 2006.

T. R. Morgan, S. Mandayam, and M. M. Jamal, Alcohol and hepatocellular carcinoma, Gastroenterology, vol.127, issue.5, pp.87-96, 2004.

S. H. Caldwell, D. M. Crespo, H. S. Kang, and A. Ams, Obesity and hepatocellular carcinoma

, Gastroenterology, vol.127, issue.5, pp.97-103, 2004.

C. Goossens, P. Nahon, L. Moyec, L. Triba, M. N. Bouchemal et al., Sequential Serum Metabolomic Profiling after Radiofrequency Ablation of Hepatocellular Carcinoma Reveals Different Response Patterns According to Etiology, Journal of proteome research, vol.15, issue.5, pp.1446-54, 2016.

R. Gao, J. Cheng, C. Fan, X. Shi, Y. Cao et al., Serum Metabolomics to Identify the Liver DiseaseSpecific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma, Sci Rep, vol.5, p.18175, 2015.

Y. Lu, C. Huang, L. Gao, Y. Xu, S. E. Chia et al., Identification of serum biomarkers associated with hepatitis B virus-related hepatocellular carcinoma and liver cirrhosis using mass-spectrometrybased metabolomics, Metabolomics, vol.11, issue.6, pp.1526-1564, 2015.

A. I. Fitian, D. R. Nelson, C. Liu, Y. Xu, M. Ararat et al., Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS. Liver international : official journal of the International Association for the Study of the Liver, vol.34, pp.1428-1472, 2014.

S. Li, H. Liu, J. Y. Lin, S. Cai, Z. Jiang et al., Metabolomics study of alcohol-induced liver injury and hepatocellular carcinoma xenografts in mice, J Chromatogr B, vol.879, issue.24, pp.2369-75, 2011.

J. D. Clarke, P. Novak, A. D. Lake, P. Shipkova, N. Aranibar et al., Characterization of hepatocellular carcinoma related genes and metabolites in human nonalcoholic fatty liver disease, Dig Dis Sci, vol.59, issue.2, pp.365-74, 2014.

A. Safaei, A. A. Oskouie, S. R. Mohebbi, M. Rezaei-tavirani, M. Mahboubi et al., Metabolomic analysis of human cirrhosis, hepatocellular carcinoma, non-alcoholic fatty liver disease and nonalcoholic steatohepatitis diseases. Gastroenterology and Hepatology from bed to bench, vol.9, p.158, 2016.

S. D. Ryder, Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults, Gut, vol.52, issue.3, pp.1-8, 2003.

K. Ikeda, S. Saitoh, A. Tsubota, Y. Arase, K. Chayama et al., Risk factors for tumor recurrence and prognosis after curative resection of hepatocellular carcinoma, Cancer, vol.71, issue.1, pp.19-25, 1993.

H. Imamura, Y. Matsuyama, E. Tanaka, T. Ohkubo, K. Hasegawa et al., Risk factors contributing to early and date phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy, J Hepatol, vol.38, issue.2, pp.200-207, 2003.

L. X. Qin and Z. Y. Tang, Recent progress in predictive biomarkers for metastatic recurrence of human hepatocellular carcinoma: a review of the literature, J Cancer Res Clin Oncol, vol.130, issue.9, pp.497-513, 2004.