The Marginal Donor: A Single-Center Experience in Orthotopic Liver Transplantation

Scuderi, Veronica; Ceriello, Antonio; Maida, Paola; Aragiusto, G.; Arenga, G.; Carfora, T.; Defez, Maurizio; Giuliani, Antonio; Monti, G. N.; Santaniello, W.; Sicoli, Federico; Calise, Fulvio

doi:10.1016/j.transproceed.2006.04.003

Cited by 10 publications

(7 citation statements)

References 17 publications

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“…Portal circulation was restored by connecting the retrohepatic venae cavae with a continuous suture and performing a termino‐terminal anastomosis with the 2 portal veins. The arterial flow and the bile duct were reconstituted with an end‐to‐end anastomosis 12…”

Section: Methodsmentioning

confidence: 99%

Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation

et al. 2006

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Ischemia-reperfusion injury (IRI) causes up to 10% of early liver failures in humans and can lead to a higher incidence of acute and chronic rejection. So far, very few studies have investigated wide gene expression profiles associated with the IRI process. The discovery of novel genes activated by IRI might lead to the identification of potential target genes for the prevention or treatment of the injury. In our study, we compared gene expression levels in reperfused livers (RL group) vs. the basal values before retrieval from the donor (basal liver [BL] group) using oligonucleotide array technology. We examined 10 biopsies from 5 livers, analyzing approximately 33,000 genes represented on the Affymetrix HG-U133APlus 2.0 oligonucleotide arrays (Affymetrix, Santa Clara, CA). About 13,000 individual genes were considered expressed in at least 1 condition. A total of 795 genes whose expression is significantly modified by ischemia-reperfusion in human liver transplantation were identified in this study. Some of them are likely to be completely activated by IRI, as they are not expressed in basal livers. The supervised gene expression analysis revealed that at least 12% of the genes involved in the apoptotic process, 12.5% of the genes involved in inflammatory processes, and 22.5% of the genes encoding for heat shock proteins are differentially expressed in RL samples vs. BL samples. Furthermore, IRI induces the upregulation of some genes' coding for adhesion molecules and integrins. In conclusion, we have identified a relevant amount of early genes regulated in the human liver after 7-9 hours of cold ischemia and 2 hours from reperfusion, many of them not having been described before in this process. Their analyses may help us to better understand the pathophysiology of IRI and to characterize potential target genes for the prevention or treatment of the liver injury in order to increase the number of patients that successfully undergo transplantation. Liver Transpl 13:99-113, 2007. © Orthotopic liver transplantation has become an effective therapeutic approach for end-stage liver diseases. Advances in surgical procedures and immunosuppression protocols have considerably improved patient survival after liver transplantation. However, ischemiareperfusion injury (IRI), an antigen-independent component of the insult to the liver, represents a major problem affecting the outcome of liver transplantation.IRI causes up to 10% of early liver failures and can lead to a higher incidence of acute and chronic rejection. Liver IRI is mediated by several processes that lead to hepatocellular damage, which is triggered when the Abbreviations: IRI, ischemia-reperfusion injury; HO-1, heme oxygenase-1; BL, basal liver; RL, reperfused liver; GO, Gene Ontology; PCR, polymerase chain reaction; IL, interleukin; CCL, cystein cistein ligand; HSP, heat shock protein.

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Section: Methodsmentioning

confidence: 99%

Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation

et al. 2006

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“…Typically the organ also exhibits a high degree of steatosis (greater than 40% macro-steatosis) and particularly, undergoes a cold ischemia time of more than 12–14 hours before reperfusion. We thus set up a preclinical model of ischemia-reperfusion injury (IRI) using organs with prolonged cold ischemia time (19 hours) to provide potentially useful information for a prompt application to clinical practice [1], [2] where there remains a desperate shortage of available organs.…”

Section: Introductionmentioning

confidence: 99%

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

et al. 2013

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Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs.

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“…This growing disparity in supply and demand has catalyzed the use of marginal grafts which are either steatotic or cholestatic. 1,2 Marginal livers have an increased susceptibility to cold and warm ischemia reperfusion (I/R) injury resulting in poor graft outcomes. 3–5 Cholestasis is a major risk factor for oxidative stress and complications of I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Cyclopamine Attenuates Acute Warm Ischemia Reperfusion Injury in Cholestatic Rat Liver: Hope for Marginal Livers

et al. 2011

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Cholestasis is a significant risk factor for immediate hepatic failure due to ischemia reperfusion (I/R) injury in patients undergoing liver surgery or transplantation. We recently demonstrated that inhibition of Hedgehog (Hh) signaling with cyclopamine (CYA) before I/R prevents liver injury. In this study we hypothesized that Hedgehog (Hh) signaling may modulate I/R injury in cholestatic rat liver. Cholestasis was induced by bile duct ligation (BDL). Seven days after BDL, rats were exposed to either CYA or vehicle for 7 d daily before subjecting them to 30 min of ischemia and 4 h of reperfusion. Expression of Hh ligands (sonic hedgehog, Patched-1 and Glioblastoma-1), assessment of liver injury, neutrophil infiltration, cytokines, lipid peroxidation, cell proliferation and apoptosis were determined. Significant upregulation of Hh ligands was seen in vehicle treated BDL rats. I/R injury superimposed on these animals resulted in markedly elevated serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin accompanied with increased neutrophil recruitment and lipid peroxidation. Preconditioning with CYA reduced the histological damage and serum liver injury markers. CYA also reduced neutrophil infiltration, proinflammatory cytokines such as TNF-α and IL-1β expression of α-smooth muscle actin and Type 1 collagen resulting in reduced fibrosis. Furthermore CYA treated animals showed reduced cholangiocyte proliferation, and apoptosis. Hepatoprotection by CYA was conferred by reduced activation of protein kinase B (Akt) and extracellular signal regulated kinase (ERK). Endogenous Hh signaling in cholestasis exacerbates inflammatory injury during liver I/R. Blockade of Hh pathway represents a clinically relevant novel approach to limit I/R injury in cholestatic marginal liver.

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The Marginal Donor: A Single-Center Experience in Orthotopic Liver Transplantation

Cited by 10 publications

References 17 publications

Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation

Wide gene expression profiling of ischemia-reperfusion injury in human liver transplantation

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Cyclopamine Attenuates Acute Warm Ischemia Reperfusion Injury in Cholestatic Rat Liver: Hope for Marginal Livers

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