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Background & Aims NKp46 + cells are major effector cells in the pathogenesis of hepatic ischemia reperfusion injury (IRI). Nevertheless, the precise role of unconventional subsets like the IL-22-producing NKp46 + cells (NK22) remains unknown. The purpose of this study was to examine the role of NK22 cells in IRI in transplantation, particularly with respect to regulation by the transcription factor ROR-gamma-t (RORγt). Methods To explore the role of NK22 cells in IRI in the absence of adaptive immunity, B6. RORγt - gfp/wt -reporter and B6. RORγt - gfp/gfp -knockout (KO) mice on a Rag KO background underwent 90min partial warm ischemia, followed by 24h of reperfusion. Results Rag KO mice that possess fully functional NKp46 + cells, and Rag-common-γ-chain-double-KO ( Rag-γc -DKO) mice that lack T, B and NKp46 + cells, were used as controls. We found that Rag-γc -DKO mice lacking NK22 cells show more severe levels of hepatocellular damage (GPT, histological injury) when compared to both Rag-RORγt -reporter and Rag KO mice that possess NK22 cells. Importantly, Rag-RORγt -reporter and Rag KO mice undergoing IRI expressed high protein levels of both IL-22 and GFP (RORγt), suggesting a protective role for RORγt + NK22 cells in IRI. Therefore, we tested the hypothesis that RORγt critically protects from IRI through the induction of hepatic NK22 cells by studying Rag-Rorγt -DKO mice under IRI conditions. We found that the lack of RORγt + NK22 cells in Rag-Rorγt -DKO mice significantly enhanced IR-induced hepatocellular injury, a phenotype that could be reversed upon adoptive transfer of Rag-Rorγt -reporter NK22 cells into DKO mice. Conclusions RORγt + NK22 cells play an important protective role in IRI in mice.

Background/Aims : Adult bone marrow contains progenitors capable of generating hepatocytes. Here a new liver failure model is introduced to assess whether bone marrow-derived progeny contribute to liver regeneration after acute hepatotoxic liver failure. Methods : Retrorsine was used to inhibit endogenous hepatocyte proliferation, before inducing acute liver failure by carbon tetrachloride. Bone marrow chimeras were generated before inducing liver failure to trace bone marrow-derived cells. Therefore, CD45 and major histocompatibility complex (MHC) class I dimorphic rat models were applied. Results : Early after acute liver failure a multilineage inflammatory infiltrate was observed, mainly consisting of granulocytes. In long-term experiments small numbers of CD90 + /CD45 − cells of donor origin occurred in clusters associated with portal triads. Bone marrow cell infusion was not able to enhance liver regeneration. Cellular hypertrophy was the predominant way of liver mass regeneration in models applying retrorsine. Conclusions : Retrorsine pretreatment did not affect sensitivity for carbon tetrachloride. A multilineage inflammatory infiltrate was observed in rats whether pretreated with retrorsine or not. Few donor cells co-expressing CD90 (THY 1) were present in recipient livers, which may resemble donor-derived hematopoietic progenitors or oval cells. No other donor cells within liver parenchyma were detected. This is in contrast to other cell infusion models of acute cell death.

Background/Aims: Hepatic artery chemoembolization was introduced in the treatment of patients with unresectable hepatocellular carcinoma waiting for liver transplantation. The rationale for this preoperative treatment was to control tumor growth during the waiting period and to improve long-term survival. This study aimed to investigate whether preoperative chemoembolization not only induces marked tumor necrosis but also has a survival benefit. Methods: In this study 21 patients with hepatocellular carcinoma who underwent pretransplant chemoembolization (group I) were compared with 21 historical control patients (group II) without preoperative chemoembolization in a case-control study. The number of pretransplant chemoembolizations in each patient in group I varied between 1 and 5 with a mean of 2.44±1.15. In addition, six patients of this group received preoperative systemic chemotherapy. Results: Overall, there were no differences in survival between the groups with and without pretransplant chemoembolization at 1 year (60.8% vs 61.5%) and at 3 years (48.4% vs 53.9%). In group I, three patients developed unexplained severe pneumonia, leading to death very early after liver transplantation. Marked tumor necrosis (>50 %) was found in 14 cases in group I. In 6 out of these 14 patients, total tumor necrosis was observed. Conclusion: Although preoperative chemoembolization or chemotherapy induced marked tumor necrosis, these patients showed no benefit in survival compared to historical controls, and appeared to be at higher risk of developing immediate postoperative infective complications.

185 THE PROTECT STUDY: EVEROLIMUS MONOTHERAPY vs. CALCINEURIN INHIBITOR-BASED THERAPY RESULTS IN PROGRESSIVE RENAL FUNCTION BENEFIT OVER 35 MONTHS IN LIVER TRANSPLANT RECIPIENTS M. Sterneck, G. Kaiser, N. Richter, N. Heyne, F. Rauchfuss, P. Neuhaus, P. Schemmer, L. Fischer, E.M. Paulus, M. Mertens, H.J. Schlitt. University Medical Center Hamburg Eppendorf, Department of Hepatobiliary and Transplant Surgery, Hamburg, Essen University Hospital, Department of General, Visceral and Transplantation Surgery, Essen, Hannover Medical School (MHH), Clinic for General, Abdominal and Transplant Surgery, Hannover, University Hospital Tuebingen, Department of General, Visceral and Transplant Surgery, Tubingen, Jena University Hospital, Department of General, Abdominal and Vascular Surgery, Jena, Charite University Medical Center Berlin, Clinic for General, Adbominal and Transplant Surgery, Berlin, University Hospital Heidelberg, Department of General Visceral and Transplant Surgery, Heidelberg, Novartis Pharma, Nurnberg, University Hospital Regensburg, Department of Surgery, Regensburg, Germany E-mail: sterneck@uke.de