title: The Need for Biomarkers in Diagnosis and Prognosis of Drug-Induced Liver Disease: Does Metabolomics Have Any Role?
abstract: Drug-induced liver injury (DILI) is a potentially fatal adverse event and the leading cause of acute liver failure in the US and in the majority of Europe. The liver can be affected directly, in a dose-dependent manner, or idiosyncratically, independently of the dose, and therefore unpredictably. Currently, DILI is a diagnosis of exclusion that physicians should suspect in patients with unexplained elevated liver enzymes. Therefore, new diagnostic and prognostic biomarkers are necessary to achieve an early and reliable diagnosis of DILI and thus improve the prognosis. Although several DILI biomarkers have been found through analytical and genetic tests and pharmacokinetic approaches, none of them have been able to display enough specificity and sensitivity, so new approaches are needed. In this sense, metabolomics is a strongly and promising emerging field that, from biofluids collected through minimally invasive procedures, can obtain early biomarkers of toxicity, which may constitute specific indicators of liver damage.
authors.affiliation: Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain; Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain.
authors.forename: Paula
authors.initials: P
authors.lastname: Iruzubieta
authors.affiliation: Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain; Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Arias-Loste
authors.affiliation: CIC bioGUNE, Metabolomics Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Barbier-Torres
authors.affiliation: CIC bioGUNE, Metabolomics Unit, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Spain.
authors.forename: Maria Luz
authors.initials: ML
authors.lastname: Martinez-Chantar
authors.affiliation: Gastroenterology and Hepatology Department, Marqués de Valdecilla University Hospital, 39008 Santander, Spain; Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), 39011 Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Crespo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D055442:Metabolome; D055432:Metabolomics / Q000379:methods*; D011379:Prognosis
chemical_list: D015415:Biomarkers
references.citation: J Proteome Res. 2007 Apr;6(4):1364-70
references.pmid: 17311441
references.citation: Toxicol Sci. 2007 May;97(1):205-13
references.pmid: 17150972
references.citation: Toxicol Appl Pharmacol. 2010 Nov 1;248(3):178-84
references.pmid: 20691717
references.citation: Comput Struct Biotechnol J. 2014 Aug 09;10(17):78-89
references.pmid: 25379137
references.citation: J Proteome Res. 2009 Jun;8(6):2882-91
references.pmid: 19378957
references.citation: Chem Biol Interact. 2004 Nov 1;150(1):35-51
references.pmid: 15522260
references.citation: Hepatology. 2006 Oct;44(4):850-6
references.pmid: 17006920
references.citation: Metabolomics. 2012;8(6):997-1011
references.pmid: 23139648
references.citation: Toxicol In Vitro. 2015 Apr;29(3):489-501
references.pmid: 25562108
references.citation: Drug Metab Dispos. 2003 Dec;31(12):1499-506
references.pmid: 14625346
references.citation: Toxicology. 2014 Oct 3;324:18-26
references.pmid: 25047351
references.citation: J Proteomics. 2014 May 30;103:227-40
references.pmid: 24747303
references.citation: Toxicol Pathol. 2005;33(4):425-33
references.pmid: 16036859
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jul 15;870(2):178-85
references.pmid: 18602877
references.citation: Hepatology. 2005 Dec;42(6):1364-72
references.pmid: 16317692
references.citation: Toxicol Lett. 2007 Sep 28;173(3):161-7
references.pmid: 17826925
references.citation: Nat Med. 2013 Apr;19(4):418-20
references.pmid: 23475203
references.citation: Xenobiotica. 1999 Nov;29(11):1181-9
references.pmid: 10598751
references.citation: J Proteome Res. 2006 Oct;5(10):2675-84
references.pmid: 17022638
references.citation: Clin Chim Acta. 2008 May;391(1-2):24-30
references.pmid: 18279672
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Aug 15;871(2):328-40
references.pmid: 18472313
references.citation: Toxicology. 2009 Feb 27;256(3):191-200
references.pmid: 19110028
references.citation: J Pharm Biomed Anal. 2004 Nov 19;36(4):841-9
references.pmid: 15533678
references.citation: Curr Opin Microbiol. 2004 Jun;7(3):296-307
references.pmid: 15196499
references.citation: Hepatology. 2008 Nov;48(5):1680-9
references.pmid: 18853438
references.citation: Anal Chem. 2007 Sep 15;79(18):6995-7004
references.pmid: 17702530
references.citation: Environ Health Perspect. 2004 May;112(7):A410-5
references.pmid: 15159214
references.citation: Chem Res Toxicol. 2006 Feb;19(2):223-33
references.pmid: 16485898
references.citation: J Pharm Biomed Anal. 2010 May 1;52(1):136-41
references.pmid: 20061116
references.citation: Clin Pharmacol Ther. 2009 Mar;85(3):331-4
references.pmid: 19129750
references.citation: PLoS One. 2014;9(3):e90416
references.pmid: 24618672
references.citation: Chem Res Toxicol. 2003 Mar;16(3):295-303
references.pmid: 12641429
references.citation: J Proteome Res. 2012 Apr 6;11(4):2427-40
references.pmid: 22384821
references.citation: Hepatology. 2013 Aug;58(2):777-87
references.pmid: 23390034
references.citation: Toxicol Appl Pharmacol. 2014 Apr 15;276(2):147-56
references.pmid: 24582690
references.citation: Nature. 2006 Apr 20;440(7087):1073-7
references.pmid: 16625200
references.citation: Semin Liver Dis. 2009 Nov;29(4):393-9
references.pmid: 19826973
references.citation: Chem Res Toxicol. 2008 Dec;21(12):2280-8
references.pmid: 19053324
references.citation: Nat Genet. 2009 Jul;41(7):816-9
references.pmid: 19483685
references.citation: JAMA. 2006 Jul 5;296(1):87-93
references.pmid: 16820551
references.citation: Toxicol Sci. 2011 Dec;124(2):487-501
references.pmid: 21920950
references.citation: Hepatology. 2008 Jun;47(6):2003-9
references.pmid: 18454504
references.citation: Clin Pharmacol Ther. 2010 Jul;88(1):45-51
references.pmid: 20182423
references.citation: Hepatology. 2006 Dec;44(6):1581-8
references.pmid: 17133470
references.citation: Clin Pharmacol Ther. 2010 Sep;88(3):394-9
references.pmid: 20668441
references.citation: Hepatology. 2002 Aug;36(2):451-5
references.pmid: 12143055
references.citation: Free Radic Biol Med. 2006 Feb 1;40(3):420-9
references.pmid: 16443156
references.citation: N Engl J Med. 2008 Feb 7;358(6):568-79
references.pmid: 18256392
references.citation: J Proteome Res. 2006 Jul;5(7):1586-601
references.pmid: 16823966
references.citation: Drug Metab Pharmacokinet. 2011;26(4):399-406
references.pmid: 21670543
references.citation: Hepatology. 2009 Jun;49(6):2001-9
references.pmid: 19475693
references.citation: Gastroenterology. 2008 Dec;135(6):1924-34, 1934.e1-4
references.pmid: 18955056
references.citation: Hepatology. 2010 Feb;51(2):615-20
references.pmid: 19839004
references.citation: J Appl Toxicol. 2014 Feb;34(2):149-57
references.pmid: 23239188
references.citation: Drug Saf. 2009;32(1):55-68
references.pmid: 19132805
references.citation: Drug Metab Rev. 2004 Oct;36(3-4):805-22
references.pmid: 15554248
references.citation: Ann Intern Med. 2002 Dec 17;137(12):947-54
references.pmid: 12484709
references.citation: Clin Infect Dis. 2000 Feb;30(2):400-1
references.pmid: 10671353
references.citation: Toxicol Appl Pharmacol. 2010 Mar 1;243(2):154-66
references.pmid: 19932708
references.citation: BMC Gastroenterol. 2009;9:99
references.pmid: 20040118
references.citation: J Proteomics. 2015 Apr 29;120:194-203
references.pmid: 25817778
references.citation: Nat Rev Gastroenterol Hepatol. 2011 Apr;8(4):202-11
references.pmid: 21386809
references.citation: PLoS One. 2014;9(5):e97249
references.pmid: 24836604
references.citation: Nat Genet. 2010 Aug;42(8):711-4
references.pmid: 20639878
references.citation: Gastroenterology. 2005 Aug;129(2):512-21
references.pmid: 16083708
references.citation: Chem Res Toxicol. 2009 Apr;22(4):699-707
references.pmid: 19256530
references.citation: Toxicol Appl Pharmacol. 2005 Apr 15;204(2):135-51
references.pmid: 15808519
references.citation: Int J Toxicol. 2011 Oct;30(5):478-91
references.pmid: 21878557
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Oct 15;969:109-16
references.pmid: 25168794
references.citation: Toxicology. 2011 Sep 5;287(1-3):29-37
references.pmid: 21645582
references.citation: Basic Clin Pharmacol Toxicol. 2006 Sep;99(3):251-60
references.pmid: 16930299
references.citation: J Appl Toxicol. 2012 Jul;32(7):505-20
references.pmid: 22131085
references.citation: Toxicol Lett. 2014 Nov 4;230(3):467-78
references.pmid: 25086301
references.citation: Aliment Pharmacol Ther. 2007 Jul 1;26(1):79-85
references.pmid: 17555424
references.citation: Curr Med Chem. 2009;16(23):3041-53
references.pmid: 19689281
references.citation: J Hepatol. 2009 Mar;50(3):511-7
references.pmid: 19155082
references.citation: Semin Liver Dis. 2002;22(2):145-55
references.pmid: 12016546
references.citation: Anal Chem. 2013 Dec 3;85(23):11326-34
references.pmid: 24127682
references.citation: Food Chem Toxicol. 2013 May;55:444-55
references.pmid: 23385219
references.citation: Drug Metab Dispos. 2009 Aug;37(8):1611-21
references.pmid: 19460945
references.citation: J Proteome Res. 2006 Jun;5(6):1448-59
references.pmid: 16739996
references.citation: Toxicol Appl Pharmacol. 2015 Oct 15;288(2):213-22
references.pmid: 26222700
references.citation: Biomark Med. 2014;8(2):147-59
references.pmid: 24521011
references.citation: J Proteome Res. 2012 Jul 6;11(7):3805-15
references.pmid: 22686559
references.citation: PLoS One. 2013;8(7):e67451
references.pmid: 23844011
references.citation: Electrophoresis. 2015 Jun 1;:null
references.pmid: 26031481
references.citation: J Proteome Res. 2006 Oct;5(10):2780-8
references.pmid: 17022649
references.citation: Nat Rev Drug Discov. 2005 Jun;4(6):489-99
references.pmid: 15931258