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24. Jahrestagung der Deutschen Transplantationsgesellschaft

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10:00 - 11:15
Wissenschaftliche Sitzung: Leber II

Vorsitz: Marcus Scherer, Regensburg; Jürgen Weitz, Dresden

10:00
V065

Vom Genotyp zum Endoskop - Personalisierte Medizin im Management von Gallengangsschäden

*Daniel Gotthardt1
1 Universitätsklinikum Heidelberg, Innere Medizin IV, Heidelberg, Deutschland
Abstract-Text :

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10:18
V066

Intra- und postoperatives Management von vaskulären Komplikationen in der Lebertransplantation

*Markus Guba1
1 Klinikum der Universität München, Klinik und Poliklinik für Chirurgie, München, Deutschland
Abstract-Text :

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10:36
V067

Weaning der Immunsuppression nach Lebertransplantation: Sinnvoll, sicher, Chancen?

*Elmar Jäckel1
1 Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Hannover, Deutschland
Abstract-Text :

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10:54
V052

A possible role of miRNAs as predictive markers for the recurrence of hepatocellular carcinoma after liver transplantation 

*Juliane Liese1, Jan  Peveling-Oberhag2, Claudia Doering3, Andreas Schnitzbauer4, Stefan Zangos5, Martin-Leo Hansmann3, Christian Mönch6, Martin W. Welker2, Stefan Zeuzem2, Wolf Otto Bechstein4, Frank Ulrich4
1 Goethe Universität Frankfurt, Medizinische Klinik III: Kardiologie, Angiologie, Nephrologie, Frankfurt, Deutschland
2 Goethe Universiät Frankfurt, Medizinische Klinik I, Frankfurt, Deutschland
3 Goethe Universität Frankfurt, Dr. Senckenberg Institut für Pathologie, Frankfurt, Deutschland
4 Goethe Universität Frankfurt, Allgemein- und Viszeralchirurgie, Frankfurt, Deutschland
5 Goethe Universität Frankfurt, Institut für Diagnostische und Interventionelle Radiologie, Frankfurt, Deutschland
6 Westpfalz Klinikum, Klinik für Allgemein-, Viszeral- und Transplatationschirurgie, Kaiserslautern, Deutschland
Abstract-Text :

With high rates of long-term survival, Liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). Nonetheless, tumor recurrence after LT remains a challenge. The aim of this retrospective study of 92 patients undergoing LT for HCC was to develop a predictive score for tumor recurrence after LT. As the key feature, microarray analysis of patients with and without HCC recurrence after LT was performed.


Of the patients, 23.9% developed a recurrence of HCC after LT, with a median disease-free survival of 10 months (3-55 months). Transplantation outside of the Milan criteria, alphafetoprotein levels and a histopathologic grade of G3 were associated with tumor recurrence. MicroRNA analysis identified significant up- regulation of 8 microRNAs and down-regulation of 5 other microRNAs in patients with tumor recurrence. Subsequently, the array data were successfully validated using real-time polymerase chain reaction. Multivariate Cox regression analysis showed that a score consisting of miR-214, miR-3187 and compliance with the Milan criteria is an independent predictor of tumor-recurrence-free survival.


Our analysis indicates that the use of a specific microRNA expression pattern in combination with limited tumor burden as defined by pre-LT radiological findings might lead to more a accurate prediction of tumor recurrence. 



11:04
V069

Regenerative response to bile duct damage and immune response to bacterial infiltration determine biliary complications after liver transplantation

*Henrik H.G. Junger1, Stefan M. Brunner1, Hans J. Schlitt1, Stefan Fichtner-Feigl1
1 University Medical Center Regensburg, , Regensburg, Deutschland
Abstract-Text :

Background: Biliary complications are a major cause of morbidity and graft failure after liver transplantation (LTx). This study aimed to clarify the molecular mechanisms behind the epithelial reaction to bile duct damage and the immune response to bacterial infiltration with respect to effects on biliary complications after LTx.


Methods: BD epithelial injury after cold storage was quantified by the BD damage score (BDDS) and correlated with patient outcome. Bacterial infiltration was determined by Fluorescence in situ Hybridisation (FISH) for bacterial antigens. Further, BD samples were analysed by immunohistochemistry for Aggrecan, Cytokeratin, CDH-18, CD8 CD14, whole genome microarray and gene set enrichment analysis.


Results: Patients with BD damage after cold storage with biliary complications had the highest frequency of graft failure (p damaged BD without biliary complications developed significantly more transplant rejection (p=.009). In damaged BDs with biliary complications reduced mRNA levels of cell-adhesion, adherens-junction and focal-adhesion-molecules (FDR q-value 0.049; 0.003; 0.049) were detected compared to damaged BDs without biliary complications, reflecting the regenerative capacity of the biliary epithelium. In accordance immunohistochemistry (IH) showed reduced expression of Aggrecan, Cytokeratin, CDH-18. Equal distribution of bacterial infiltration of BDs was observed in FISH analysis, however, mRNA analysis detected enrichment of gene programs characterizing immune response to bacterial infection and FC-gamma mediated phagocytosis (FDR q-value 8.4*10-4; 0.046). Corresponding and consecutively IH showed increased numbers of CD8 , CD14 cells in BDs with enhanced regenerative capacity of the biliary epithelium.


Conclusions: These studies show that BD damage detected after cold storage is a prognosticator for biliary complications and graft loss after LTx. Functional regenerative capacities of the biliary epithelium and enhanced immune response to bacterial infiltration are able to rescue damaged BDs and prevent biliary complications after LTx.