title: High preoperative recipient plasma 7beta-hydroxycholesterol is associated with initial poor graft function after liver transplantation.
abstract: Oxidative stress is implicated in the pathogenesis of hepatic ischemia-reperfusion injury, a major determinant of initial poor graft function (IPGF) after orthotopic liver transplantation (OLT). We prospectively investigated the association between the recipient plasma preoperative oxidative stress and the occurrence of IPGF after deceased-donor OLT and indirectly studied the source-hepatic or extra-hepatic-of systemic oxidative stress in vivo in cirrhosis. We used a recently developed specific and sensitive mass spectrometry assay to measure 7beta-hydroxycholesterol and 7-ketocholesterol (oxysterols), markers of oxidative stress, in biological matrices. At univariate analysis, preoperative recipient 7beta-hydroxycholesterol plasma concentration was significantly higher in transplants with subsequent IPGF (n = 9) compared with those with initial good graft function (IGGF; n = 23) [mean +/- SD: 30.63 +/- 26.42 and 11.57 +/- 15.76 ng/mL, respectively] (P = 0.017). In a logistic regression model, which included also the Model for End-Stage Liver Disease (MELD) score, 7beta-hydroxycholesterol plasma concentration was an independent predictor of IPGF with an odds ratio of 1.17 (95% CI, 1.02-1.33, P = 0.028). Patients with cirrhosis (n = 32) had increased oxysterol plasma levels compared with healthy controls (n = 49); livers with cirrhosis (n = 21), however, had oxysterol content comparable with normal livers obtained from organ donors (n = 19). Oxysterols persisted elevated in plasma 1 month after OLT (n = 23). In conclusion, cirrhosis presents upregulated systemic oxidative stress likely of extrahepatic source that is associated with graft failure after OLT.
authors.affiliation: Department of Clinical Medicine, Division of Gastroenterology, University La Sapienza, Via del Policlinico 155, 00161 Rome, Italy.
authors.forename: Stefano Ginanni
authors.initials: SG
authors.lastname: Corradini
authors.forename: Fausta
authors.initials: F
authors.lastname: Micheletta
authors.forename: Silvia
authors.initials: S
authors.lastname: Natoli
authors.forename: Massimo
authors.initials: M
authors.lastname: Iappelli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.forename: Rosanna
authors.initials: R
authors.lastname: De Marco
authors.forename: Walter
authors.initials: W
authors.lastname: Elisei
authors.forename: Maria
authors.initials: M
authors.lastname: Siciliano
authors.forename: Massimo
authors.initials: M
authors.lastname: Rossi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Berloco
authors.forename: Adolfo Francesco
authors.initials: AF
authors.lastname: Attili
authors.forename: Ulf
authors.initials: U
authors.lastname: Diczfalusy
authors.forename: Luigi
authors.initials: L
authors.lastname: Iuliano
mesh_terms: D015415:Biomarkers / Q000097:blood; D051799:Delayed Graft Function / Q000097:blood* / Q000150:complications; D005500:Follow-Up Studies; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007653:Ketocholesterols / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood* / Q000601:surgery; D017093:Liver Failure / Q000097:blood* / Q000209:etiology; D016031:Liver Transplantation; D013058:Mass Spectrometry; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D006888:Hydroxycholesterols; D007653:Ketocholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C003001:7-ketocholesterol