Recipient perioperative cholesterolaemia and graft cholesterol metabolism gene expression predict liver transplant outcome
Corresponding Author
Stefano Ginanni Corradini
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Correspondence
Stefano Ginanni Corradini, MD, PhD, Via Asmara 9-B, 00199 Rome, Italy
Tel: +39 06 4997 2086
Fax: +39 06 445 3319
e-mail: [email protected]
Search for more papers by this authorMaria Siciliano
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorLucia Parlati
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAntonio Molinaro
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAlfredo Cantafora
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorEdoardo Poli
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorGianluca Mennini
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorFabio Melandro
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAnna Rita Vestri
Department of Public Health and Infectious Disease, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorManuela Merli
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorPaolo Bianco
Department of Molecular Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAlessandro Corsi
Department of Molecular Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorPierluigi Toniutto
Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
Search for more papers by this authorDavide Bitetto
Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
Search for more papers by this authorEdmondo Falleti
Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
Search for more papers by this authorAdolfo Francesco Attili
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorPasquale Berloco
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorMassimo Rossi
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorCorresponding Author
Stefano Ginanni Corradini
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Correspondence
Stefano Ginanni Corradini, MD, PhD, Via Asmara 9-B, 00199 Rome, Italy
Tel: +39 06 4997 2086
Fax: +39 06 445 3319
e-mail: [email protected]
Search for more papers by this authorMaria Siciliano
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorLucia Parlati
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAntonio Molinaro
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAlfredo Cantafora
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorEdoardo Poli
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorGianluca Mennini
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorFabio Melandro
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAnna Rita Vestri
Department of Public Health and Infectious Disease, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorManuela Merli
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorPaolo Bianco
Department of Molecular Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAlessandro Corsi
Department of Molecular Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorPierluigi Toniutto
Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
Search for more papers by this authorDavide Bitetto
Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
Search for more papers by this authorEdmondo Falleti
Medical Liver Transplantation Unit, Internal Medicine, University of Udine, Udine, Italy
Search for more papers by this authorAdolfo Francesco Attili
Division of Gastroenterology, Department of Clinical Medicine, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorPasquale Berloco
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorMassimo Rossi
Department of General Surgery “Paride Stefanini”, University “Sapienza” of Rome, Rome, Italy
Search for more papers by this authorAbstract
Background & Aims
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.
Supporting Information
| Filename | Description |
|---|---|
| liv12351-sup-0001-Supinfo.docWord document, 97 KB | Data S1. Materials and Methods. Table S1. Sequences of primer pairs (sense and anti-sense respectively) used for amplifying the genes of interest (GOI) and the three internal control genes (GAPDH, HMBS and HPRT1) used for the normalization procedure with the geometric averaging of multiple control genes. Table S2. Multivariate logistic regression analysis of pre-operative predictive factors of 3- and 12-month graft failure after transplantation in the study group. Table S3. Pre-ischaemia and post-reperfusion graft cholesterol metabolism gene expression in relation to pre-transplant recipient serum total cholesterol level in functioning grafts in the study group. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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