Complement System Activation During Orthotopic Liver Transplantation in Man

Rønholm, Ebbe; Tomasdottir, Hildur; Runeborg, Jens; Bengtsson, Anders; Bengtson, J. P.; Stenqvist, O.; Friman, Styrbjörn

doi:10.1097/00007890-199457110-00010

Cited by 27 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to so many liver transplantations, it is crucial to determine the mechanisms responsible for the proper function of this organ after transplantation. Over the years, researchers have shown that one of the most important mechanisms affecting the process of organ transplantation, including the liver, is the selected components of the complement system [13][14][15][16][17][18][19][20][21][22][23]26].…”

Section: Discussionmentioning

confidence: 99%

“…Ronholm et al [22] studied changes in C3a, C5a, and C5b-9 levels before transplantation, one minute before reperfusion, and 1-2 min, 5 min, 30 min, and 6-12 h after the beginning of reperfusion. As in our studies, the lowest concentration of the studied factors was observed before transplantation, but they did not report any significant changes in C3a levels before the reperfusion of the transplanted liver.…”

Section: Discussionmentioning

confidence: 99%

“…Levels of C5a during surgery remained unchanged when compared to the pre-operative concentration. Our determinations were performed using ELISA and covered a much larger study group, while Ronholm et al [22] included 16 people and the concentration of C3a and C5a antigens were measured by radioimmunoassay (RIA). Additionally, we measured the C5b-9 concentration, while Ronholm et al indicated its biological activity.…”

Section: Discussionmentioning

confidence: 99%

“…It is believed that factors contributing to the migration, adhesion, differentiation, and survival of cells significantly impact the liver transplant process. Therefore, it is postulated that the presence of an immunologically incompatible organ and its damage in the mechanism of ischemia-reperfusion injury (IRI) may be the result of the impaired activation of chemokines [1][2][3] and growth factors [4][5][6][7][8][9][10][11][12], but primarily the components of the complement system [13][14][15][16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Biomarkers of the Complement System Activation (C3a, C5a, sC5b-9) in Serum of Patients before and after Liver Transplantation

et al. 2023

View full text Add to dashboard Cite

The liver has a huge impact on the functioning of our body and the preservation of homeostasis. It is exposed to many serious diseases, which may lead to the chronic failure of this organ, which is becoming a global health problem today. Currently, the final form of treatment in patients with end-stage (acute and chronic) organ failure is transplantation. The proper function of transplanted organs depends on many cellular processes and immune and individual factors. An enormous role in the process of acceptance or rejection of a transplanted organ is attributed to, among others, the activation of the complement system. The aim of this study was the evaluation of the concentration of selected biomarkers’ complement system activation (C3a, C5a, and sC5b-9 (terminal complement complex)) in the serum of patients before and after liver transplantation (24 h, two weeks). The study was conducted on a group of 100 patients undergoing liver transplantation. There were no complications during surgery and no transplant rejection in any of the patients. All patients were discharged home 2–3 weeks after the surgery. The levels of all analyzed components of the complement system were measured using the ELISA method. Additionally, the correlations of the basic laboratory parameters—C-reactive protein (CRP), hemoglobin (Hb), total bilirubin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGTP), and albumin—with the parameters of the complement system (C3a, C5a, and sC5b-9) were determined. In our study, changes in the concentrations of all examined complement system components before and after liver transplantation were observed, with the lowest values before liver transplantation and the highest concentration two weeks after. The direct increase in components of the complement system (C3a, C5a, and sC5b-9) 24 h after transplantation likely affects liver damage after ischemia-reperfusion injury (IRI), while their increase two weeks after transplantation may contribute to transplant tolerance. Increasingly, attention is being paid to the role of C3a and CRP as biomarkers of damage and failure of various organs. From the point of view of liver transplantation, the most interesting correlation in our own research was found exactly between CRP and C3a, 24 h after the transplantation. This study shows that changes in complement activation biomarkers and the correlation with CRP in blood could be a prognostic signature of liver allograft survival or rejection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biomarkers of the Complement System Activation (C3a, C5a, sC5b-9) in Serum of Patients before and after Liver Transplantation

et al. 2023

View full text Add to dashboard Cite

show abstract

“…These findings are in accordance with other clinical studies of complement activation during OLT without the use of VVBP. 19,20 Factors responsible for complement system activation could be reperfusion injury, immunological reactions and the use of other devices such as the cell saver. However, based on the results of in vitro studies by our group, where we found significant reduction of complement activation in HC systems compared to NC systems, 18 it is reasonable to believe that the VVBP circuit may also contribute to activation of the complement system in the in vivo situation, as the experimental conditions used in the in vitro study were comparable with respect to key factors such as flow rate and temperature.…”

Section: Discussionmentioning

confidence: 99%

The significance of heparin-coated veno-venous bypass circuits in liver transplantation

Scholz¹,

Solberg

Okkenhaug³

et al. 2002

Perfusion

View full text Add to dashboard Cite

We studied the effects of veno-venous bypass (VVBP) circuit surface heparinization on the activation of the plasma defence systems (coagulation, fibrinolysis, kallikrein-kinin and complement) and leukocyte activation in a prospective randomized study in 20 patients during and 1 day after liver transplantation (OLT). To our knowledge, this is the first study of this kind where the possible benefits of surface heparinization of the VVBP circuit in OLT have been investigated. Twenty patients were randomized to either heparin-coated (HC) VVBP equipment or to otherwise identical noncoated (NC) circuits. Five blood samples were drawn during the OLT procedure: one just before VVBP, three during VVBP and one 5 min after portal venous reperfusion (PVR). A further sample was taken 1 day after the operation. Components of the blood coagulation, fibrinolytic and kallikrein-kinin systems were analysed using functional assays (chromogenic peptide substrate assays) or enzyme immunoassays (EIA). Complement system factors and granulocyte activation, represented by myeloperoxidase (MPO) release, were analyzed by EIA. Activation of the plasma defence systems occurred in both groups at an early stage during OLT and a further activation occurred 5 min after PVR. MPO levels were slightly elevated 5 min after PVR. However, no significant differences between the two groups were observed. Significant activation of the humoral defense systems was found in both groups during OLT. A considerably larger study, including at least 330 patients, is necessary to fully assess the possible benefits of surface heparinization of the VVBP circuit.

show abstract

Complement membrane attack complex and hemodynamic changes during human orthotopic liver transplantation

et al. 2004

View full text Add to dashboard Cite

on behalf of the Leeds Liver GroupHemodynamic changes and elevation of intracellular calcium following reperfusion in human liver transplantation occur rapidly and do not match the time course of cytokine expression, therefore, we postulate involvement of other, pre-formed substances, such as complement. We studied 40 adult patients undergoing liver transplantation. Blood was drawn for estimation of C3, C4, C3 degradation product, membrane attack complex, and CH100 levels and elastase (a marker of neutrophil activation) at induction of anesthesia, 5 minutes before reperfusion, 5 minutes and 60 minutes after reperfusion. Cardiac output was measured by thermodilution and systemic vascular resistance was calculated at these same time points. There was a significant rise in C5b-9 membrane attack complex (P ‫؍‬ .0012) with a corresponding fall in C3 (P ‫؍‬ .0013) and C4 (P ‫؍‬ .0002) levels and a rise in C3 degradation product levels (P ‫؍‬ .0006). There was no significant change in CH100. These changes very closely followed the hemodynamic changes of a significant fall in systemic vascular resistance index (P ‫؍‬ .0024) and increase in cardiac index (P ‫؍‬ .0005). Elastase rose from 356 ؎ 53 to 557 ؎ 40 g/L (P < .0001). There is complement activation and neutrophil activation at reperfusion in liver transplantation. Dilution alone cannot explain the fall in C3 and C4 levels as there is a corresponding increase in membrane attack complex and C3 degradation product levels with time. As both C3 and C4 are consumed, the classical pathway must be active, though alternative and lectin activated pathways may also be involved. These findings may, at least in part, explain the hemodynamic changes typically seen at reperfusion in liver transplantation. (Liver Transpl 2004;10:273-278.)

show abstract

Complement System Activation During Orthotopic Liver Transplantation in Man

Cited by 27 publications

References 0 publications

Biomarkers of the Complement System Activation (C3a, C5a, sC5b-9) in Serum of Patients before and after Liver Transplantation

Biomarkers of the Complement System Activation (C3a, C5a, sC5b-9) in Serum of Patients before and after Liver Transplantation

The significance of heparin-coated veno-venous bypass circuits in liver transplantation

Complement membrane attack complex and hemodynamic changes during human orthotopic liver transplantation

Contact Info

Product

Resources

About