Serum Markers of Hepatocyte Death and Apoptosis Are Non Invasive Biomarkers of Severe Fibrosis in Patients with Alcoholic Liver Disease 英文参考文献.docVIP

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Serum Markers of Hepatocyte Death and Apoptosis Are Non Invasive Biomarkers of Severe Fibrosis in Patients with Alcoholic Liver Disease 英文参考文献.doc

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Serum Markers of Hepatocyte Death and Apoptosis Are Non Invasive Biomarkers of Severe Fibrosis in Patients with Alcoholic Liver Disease 英文参考文献

SerumMarkersofHepatocyteDeathandApoptosisAre NonInvasiveBiomarkersofSevereFibrosisinPatients withAlcoholicLiverDisease VanessaJeannetteLavallard1,2,3.,Ste′phanieBonnafous1,3.,Ste′phaniePatouraux1,2,4 ,Marie-Christine Saint-Paul1,2,4,De′borahRousseau1,2,RodolpheAnty1,2,3,YannickLeMarchand-Brustel1,2,3 ,Albert Tran1,2,3,PhilippeGual1,2,3 * 1Team8,%Hepaticcomplicationsofobesity,INSERM,U895,Nice,France,2FacultyofMedicine,UniversityofNice-Sophia-Antipolis,Nice,France,3DigestiveCenter, CentreHospitalierUniversitaireofNice,Nice,France,4BiologicalCenter,CentreHospitalierUniversitaireofNice,Nice,France Abstract Background:Quantificationofhepatotocytedeathisusefultoevaluatetheprogressionofalcoholicliverdiseases.Ouraims weretoquantifyandcorrelatethecirculatinglevelsofCytokeratin18(CK18)anditscaspases-generatedfragmenttodisease severityinheavyalcoholics. Methodology/PrincipalFindings:CK18andCK18-fragmentwereevaluatedintheserumof143heavyalcoholics.Serum levelsofmarkersofhepatocytedeath(CK18),apoptosis(CK18fragment)andnecrosis(CK18-CK18fragment)increasedin patientswithseverefibrosiscomparedtopatientswithmildfibrosis.ThesemarkersstronglycorrelatedwithMallory-Denk bodies,hepatocyteballooning,fibrosisandwithhepaticTNFaandTGFbassessedintheliverof24patients.Elevatedlevels ofserumhepatocytedeathandapoptoticmarkerswereindependentriskfactorsinpredictingseverefibrosisinamodel combiningalkalinephosphatase,bilirubin,prothrombinindex,hyaluronate,hepatocytedeathandapoptoticmarkers.The levelofmarkersofhepatocytedeathandapoptosishadanareaunderthereceivingoperatorcurvethatpredictedsevere fibrosisof0.84and0.76,respectively. Conclusion/Significance: Death of hepatocytes can be easily evaluated with serum markers and correlated with severe fibrosis in heavy alcohol drinkers. These biomarkers could be useful to rapidly evaluate liver injuries and the efficacy of therapies. Citation:LavallardVJ,BonnafousS,PatourauxS,Saint-PaulM-C,RousseauD,etal.(2011)SerumMarkersofHepatocyteDeathandApoptosisAreNonI