High preoperative recipient plasma 7beta-hydroxycholesterol is associated with initial poor graft function after liver transplantation.
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.
Corradini
Stefano Ginanni
SG
Department of Clinical Medicine, Division of Gastroenterology, University La Sapienza, Via del Policlinico 155, 00161 Rome, Italy.
Micheletta
Fausta
F
Natoli
Silvia
S
Iappelli
Massimo
M
Di Angelantonio
Emanuele
E
De Marco
Rosanna
R
Elisei
Walter
W
Siciliano
Maria
M
Rossi
Massimo
M
Berloco
Pasquale
P
Attili
Adolfo Francesco
AF
Diczfalusy
Ulf
U
Iuliano
Luigi
L
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
D015415:Biomarkers; D006888:Hydroxycholesterols; D007653:Ketocholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; C003001:7-ketocholesterol