KFO 117: Optimierung der Leberlebendspende
Zusammenfassung der Projektergebnisse
The central aim of the Clinical Research Unit (KFO) was to optimize living-related liver transplantation in a multi-disciplinary approach to increase its safety for both donor and recipient. To achieve this goal, the projects aimed at - improving donor and recipient selection (projects A-I, A-IV, B-VII), - improving preoperative planning (A-II, B-II), - improving conditioning of organs (A-III) and - improving postoperative course and outcome by reduction of graft injury and enhancement of regeneration (A-IV, B-I to B-VII). Improvement of donor selection: Researchers of project A-I, together with their surgical colleagues and colleagues from the Universities in Tübingen, Cologne and Jena, developed a reliable and valid “questionnaire for the assessment of psychosocial eligibility of living liver donors” and a specific “quality of life questionnaire for living donors” (for which psychometric testing is in progress) in order to improve donor selection and psychosocial monitoring; in the second funding period, studies were extended to living kidney donors. Improvement of recipient selection: Researchers of project A-IV in collaboration with the Institute of Physiology and the Department of Gastroenterology and Hepatology showed that the modulated host milieu of the non-neoplastic liver in patients with hepatocellular carcinoma (HCC) predisposes for recurrence and that one of the crucial pathways involved is the HIF-1 pathway. The concept of biomarker identification for HCC was further developed and contributed to the establishment of the PROFILE consortium. Improvement of preoperative planning: Researchers of project A-II optimized liver imaging and computer-assisted analysis, especially with respect to detailed, automated 3D representation of the hepatic vascular trees for the optimization of preoperative planning and with respect to local and global liver growth to enhance the understanding of regeneration patterns. The latter part was complemented by the experimental project B-II, which studied the influence of outflow obstruction on liver regeneration in a rat model. A highly innovative part of project A-II, done in collaboration with the Erwin-Hahn-Institute (Essen), demonstrated the technical feasibility of visualizing the human liver with 7T MRI; this approach will be continued. Improvement of graft conditioning: To avoid reinfection of the graft in a hepatitis B-positive recipient, project A-III developed a short-term vaccination protocol and showed that living donor liver transplantation from an immunized donor resulted in an adoptive HBV immune transfer from the donor to the recipient. Subsequently, an HCV prototype vaccine based on HBV capsid-like particles presenting mimotopes of the HCV E2-envelope protein was developed; this prototype vaccine was highly immunogenic in mice, thus representing a promising approach for a future vaccine against hepatitis C. Reduction of graft injury and improvement of regeneration: In collaboration with colleagues from the Department of Surgery, researchers of project B-I transferred in vitro findings for the improvement of organ preservation to the transplantation setting. A new preservation solution developed by this group was tested in animal models and has now entered clinical studies (in cardioplegia) or is about to enter clinical studies (in living-related kidney transplantation, study being prepared in Essen). Researchers from the Departments of Gastroenterology and Hepatology and the Institute of Pathology complemented the studies on graft protection/regeneration by studying the roles of the Toll-like receptor system, NF-κB, erythropoietin and VEGF (B-IV), survivin (B-V) and of fatty acids/steatosis (B-VII). Database: In the second funding period project S-I coordinated the design and set-up of a central database which is embedded into the hospital information system (HIS) medico//s. It contains more than 200 harmonized items derived from the local data collections and covers important aspects of living-related and/or cadaveric liver transplantations. This database will greatly facilitate future clinical studies in living donor liver transplantation and in liver transplantation in general.
