Early Postoperative Response of Cytokines in Liver Transplant Recipients

Hassan, Laila; Bueno, Pablo; Ferrón-Celma, I.; Ramia, J. M.; Garrote, Daniel; Muffak, Karim; Barrera, L.; Villar, Jesús; García-Navarro, Ana; Mansilla, Alfonso; Bravo, Miguel Ángel Gómez; Bernardos, Á.; Ferrón, José Antonio

doi:10.1016/j.transproceed.2006.08.054

Cited by 20 publications

(19 citation statements)

References 8 publications

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“…Other recently published studies have failed to demonstrate a significant increase in cytokine levels during graft reperfusion16 or a cytokine gene polymorphism associated with PRS 17. The majority of the trials demonstrated increased levels of cytokines later in the hospital course 9, 18. These studies found that cytokine levels increased at least 1 hour after graft reperfusion and persisted for several days after surgery.…”

Section: Discussionmentioning

confidence: 98%

Release of cytokines and hemodynamic instability during the reperfusion of a liver graft

et al. 2011

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The objectives of this prospective, observational study were (1) to determine whether a transplanted liver graft releases proinflammatory cytokines into the systemic circulation upon reperfusion and (2) to determine whether they contribute to any subsequent hemodynamic instability observed after graft reperfusion (if this release occurs). Blood samples from 17 consecutive patients undergoing liver transplantation were analyzed for cytokines, including tumor necrosis factor a (TNFa), interleukin-1b (IL-1b), IL-2, IL-6, and IL-8. Blood samples were obtained from the radial artery, portal vein, and flush blood (a sample taken from a catheter placed above the infrahepatic inferior vena cava clamp). The amount of catecholamines necessary to maintain a mean arterial pressure between 65 and 75 mm Hg during graft reperfusion was compared with the level of cytokines. A statistical analysis was performed with the least squares method, Kendall's tau-b test, and regression analysis. We demonstrated that flush blood from the liver grafts contained a significant amount and variety of cytokines. Most of these were removed by graft irrigation. The concentration of TNF-a in samples obtained from flush blood at the end of liver irrigation was significantly higher than the concentration in samples obtained from the radial artery (P ¼ 0.0067) or portal vein (P ¼ 0.0003) before reperfusion. This correlated directly with the amount of catecholamines used to treat hemodynamic instability. Although there were increased levels of IL-1b, IL-2, and IL-8 in the flush blood, there was no statistically significant correlation between the levels of these cytokines and the amount of catecholamines used. Liver

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Section: Discussionmentioning

confidence: 98%

Release of cytokines and hemodynamic instability during the reperfusion of a liver graft

et al. 2011

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“…EAD is thought to be a secondary or downstream effect of ischemia/reperfusion (I/R) injury, which is associated with acute cellular damage, cell death, apoptosis, oxidative damage from the creation of reactive oxygen species, and severe inflammatory responses occurring within the liver (23)(24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

Genomic Profiles and Predictors of Early Allograft Dysfunction After Human Liver Transplantation

Kurian

Fouraschen

Langfelder

et al. 2015

American Journal of Transplantation

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y These authors contributed equally to this manuscript.Early hepatic allograft dysfunction (EAD) manifests posttransplantation with high serum transaminases, persistent cholestasis, and coagulopathy. The biological mechanisms are poorly understood. This study investigates the molecular mechanisms involved in EAD and defines a gene expression signature revealing different biological pathways in subjects with EAD from those without EAD, a potential first step in developing a molecular classifier as a potential clinical diagnostic. Global gene expression profiles of 30 liver transplant recipients of deceased donor grafts with EAD and 26 recipients without graft dysfunction were investigated using microarrays of liver biopsies performed at the end of cold storage and after graft reperfusion prior to closure. Results reveal a shift in inflammatory and metabolic responses between the two time points and differences between EAD and non-EAD. We identified relevant pathways (PPARa and NF-kB) and targets (such as CXCL1, IL1, TRAF6, TIPARP, and TNFRSF1B) associated with the phenotype of EAD. Preliminary proof of concept gene expression classifiers that distinguish EAD from non-EAD patients, with Area Under the Curve (AUC) >0.80 were also identified. This data may have mechanistic and diagnostic implications for EAD.

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“…Perioperative secretion of cytokines in patients undergoing liver transplantation is closely related to the graft prognosis. Boros et al (14), found that IL-1, IL 6, and IL-8 concentrations in the hepatic vein at the time of reperfusion were higher in patients who suffered poor postoperative graft function, and Hassan et al (15) reported that plasma concentrations of IL-6 and IL-10 might be useful as predictive indicators for postoperative complications in liver transplant recipients. Mueller et al (16) also reported that several cytokines secreted during liver transplantation, including IL-2, were correlated with postoperative graft function.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Child-Turcotte-Pugh Classification and the Model for End-stage Liver Disease Score as Predictors of the Severity of the Systemic Inflammatory Response in Patients Undergoing Living-donor Liver Transplantation

et al. 2011

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The aim of this study was to evaluate and compare the Child-Turcotte-Pugh (CTP) classification system and the model for end-stage liver disease (MELD) score in predicting the severity of the systemic inflammatory response in living-donor liver transplantation patients. Recipients of liver graft were allocated to a recipient group (n = 39) and healthy donors to a donor group (n = 42). The association between the CTP classification, the MELD scores and perioperative cytokine concentrations in the recipient group was evaluated. The pro-inflammatory cytokines measured included interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α; the anti-inflammatory cytokines measured included IL-10 and IL-4. Cytokine concentrations were quantified using sandwich enzyme-linked immunoassays. The IL-6, TNF-α, and IL-10 concentrations in the recipient group were significantly higher than those in healthy donor group patients. All preoperative cytokine levels, except IL-6, increased in relation to the severity of liver disease, as measured by the CTP classification. Additionally, all cytokine levels, except IL-6, were significantly correlated preoperatively with MELD scores. However, the correlations diminished during the intraoperative period. The CTP classification and the MELD score are equally reliable in predicting the severity of the systemic inflammatory response, but only during the preoperative period.

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Early Postoperative Response of Cytokines in Liver Transplant Recipients

Cited by 20 publications

References 8 publications

Release of cytokines and hemodynamic instability during the reperfusion of a liver graft

Release of cytokines and hemodynamic instability during the reperfusion of a liver graft

Genomic Profiles and Predictors of Early Allograft Dysfunction After Human Liver Transplantation

Comparison of the Child-Turcotte-Pugh Classification and the Model for End-stage Liver Disease Score as Predictors of the Severity of the Systemic Inflammatory Response in Patients Undergoing Living-donor Liver Transplantation

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