title: Recipient perioperative cholesterolaemia and graft cholesterol metabolism gene expression predict liver transplant outcome.
abstract: OBJECTIVE
  We analysed for the first time whether recipient perioperative serum total cholesterol (sTC) concentration is associated with liver transplantation outcome.
  
  
  METHODS
  We studied noncholestatic cirrhotics submitted to primary deceased-donor liver transplantation in a prospective group (n=140) from Rome and in a validation retrospective cohort (n=157) from Udine, Italy. Pre-ischaemia and post-reperfusion cholesterol metabolism gene mRNA was measured by RT-PCR in 74 grafts of the study group.
  
  
  RESULTS
  At Cox regression analysis, independently from confounders including recipient MELD score, the recipient pre-operative sTC pooled quintiles 2-5, compared with the lowest quintile showed HR (95% CI) and significances for overall graft loss (GL) of 0.215 (0.104-0.444) P<0.001 in the study group and 0.319 (0.167-0.610) P=0.001 in the validation cohort. Analysing sTC as a continuous variable, the risk of overall GL for every 10-mg/dl decrease in pre-operative sTC increased by 13% and by 9% in the study group and in the validation cohort respectively. In the study group, independent associations at multivariate analyses were: (a) high graft pre-ischaemia expression of INSIG-1, which indicates hepatocellular cholesterol depletion, with post-reperfusion graft necrosis; (b) GL with inadequate graft post-reperfusion response to cholesterol depletion, shown by a failure to reduce the PCSK9 to LDLR expression ratio; (c) GL with a relative increase of sTC on post-operative day-7, selectively because of the LDL fraction, which indirectly suggests poor cholesterol uptake from blood.
  
  
  CONCLUSIONS
  Low recipient pre-transplant sTC concentration, its post-operative day-7 increase and a genetically determined low graft cholesterol availability predict poor liver transplant outcome.
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University "Sapienza" of Rome, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ginanni Corradini
authors.forename: Maria
authors.initials: M
authors.lastname: Siciliano
authors.forename: Lucia
authors.initials: L
authors.lastname: Parlati
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cantafora
authors.forename: Edoardo
authors.initials: E
authors.lastname: Poli
authors.forename: Gianluca
authors.initials: G
authors.lastname: Mennini
authors.forename: Fabio
authors.initials: F
authors.lastname: Melandro
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Vestri
authors.forename: Manuela
authors.initials: M
authors.lastname: Merli
authors.forename: Paolo
authors.initials: P
authors.lastname: Bianco
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corsi
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Toniutto
authors.forename: Davide
authors.initials: D
authors.lastname: Bitetto
authors.forename: Edmondo
authors.initials: E
authors.lastname: Falleti
authors.forename: Adolfo Francesco
authors.initials: AF
authors.lastname: Attili
authors.forename: Pasquale
authors.initials: P
authors.lastname: Berloco
authors.forename: Massimo
authors.initials: M
authors.lastname: Rossi
mesh_terms: D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007558:Italy; D008103:Liver Cirrhosis / Q000601:surgery*; D016031:Liver Transplantation / Q000379:methods* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D059035:Perioperative Period; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism; D012044:Regression Analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: C573412:LDLR protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D002784:Cholesterol; D003404:Creatinine; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: HMGCR; LDLR; NPC1L1; PCSK9; SREBF2; cholesterolemia; cirrhosis; graft survival; liver transplantation; serum cholesterol