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Tobias J Weismüller,
Panagiotis Fikatas,
Jan Schmidt, Ana P Barreiros,
Gerd Otto,
Susanne Beckebaum,
Andreas Paul,
Markus N Scherer,
Hartmut H Schmidt,
Hans J Schlitt,
Peter Neuhaus,
Jürgen Klempnauer,
Johann Pratschke,
Michael P Manns,
Christian P Strassburg
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ABSTRACT: Since the introduction of model for end-stage liver disease (MELD) in 2006, post-orthotopic liver transplantation (OLT) survival in Germany has declined. The aim of this study was to evaluate risk factors and prognostic scores for outcome. All adult OLT recipients in seven German transplant centers after MELD implementation (December 2006-December 2007) were included. Recipient data were analyzed for their influence on 1-year outcome. A total of 462 patients (mean calculated MELD = 20.5, follow-up: 1 year) were transplanted for alcoholic cirrhosis (33.1%), hepatocellular carcinoma (26.6%), Hepatitis-C (17.1%), Hepatitis-B (9.5%), primary sclerosing cholangitis (5.6%) and late graft-failure after first OLT before December 2006 (8.7%). 1-year patient survival was 75.8% (graft survival 71.2%) correlating with MELD parameters and serum choline esterase. MELD score >30 [odds ratio (OR) = 4.17, confidence interval: 2.57-6.78, 12-month survival = 52.6%, c-statistic = 0.669], hyponatremia (OR = 2.07), and pre-OLT hemodialysis (OR = 2.35) were the main death risk factors. In alcoholic cirrhosis (n = 153, mean MELD = 21.1) and hepatocellular carcinoma (n = 123, mean MELD = 13.5), serum bilirubin and the survival after liver transplantation score were independent outcome parameters, respectively. MELD >30 currently represents a major risk factor for outcome. Risk factors differ in individual patient subgroups. In the current German practice of organ allocation to sicker patients, outcome prediction should be considered to prevent results below acceptable standards.
Transplant International 01/2011; 24(1):91-9. · 2.92 Impact Factor
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Tim Zimmermann,
Maria Hoppe-Lotichius,
Vuk Tripkovic, Ana P Barreiros,
Thomas C Wehler,
Anca Zimmermann,
Jörn M Schattenberg,
Michael Heise,
Stefan Biesterfeld,
Peter R Galle,
Gerd Otto,
Marcus Schuchmann
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ABSTRACT: Long term immunosuppression and therapy of acute rejections result in a 20-120-fold increased risk to develop Non Hodgkin lymphoma (NHL). Since immunosuppressive therapy and immunological disorders are major risk factors for the development of NHL in the non-transplant population we aimed to analyze risk factors for PTLD in our cohort of liver transplanted (LT) patients.
We analyzed retrospectively 431 patients liver transplanted between 1998 and 2008.
PTLD was diagnosed in eleven of 431 patients (2.6%). PTLD, especially late PTLD, was significantly more frequent in patients who received steroids before LT (Kaplan-Meier: p<0.001). Moreover PTLD in immunocompromised patients with preoperative steroid treatment occurred at a significantly younger age (49.5+/-4.7 years) compared to patients without steroids (60.6+/-5.1 years; p=0.006). Multivariate analysis revealed pretransplant steroid treatment and liver transplantation for autoimmune hepatitis as main risk factors for the development of PTLD after liver transplantation (p<0.001).
Liver transplanted patients who received steroids before LT due to immunological disorders and patients with autoimmune hepatitis seem to be at particular high risk to develop PTLD. Prospective cohort studies including immunoepidemiologic investigations of abnormalities of cellular, humoral and innate immunity should be carried out to identify predictive factors and patients at risk.
European Journal of Internal Medicine 06/2010; 21(3):208-15. · 2.00 Impact Factor
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Jürgen Kuball,
Matthias Theobald,
Edite Antunes Ferreira,
Georg Hess,
Jürgen Burg,
Giancarlo Maccagno, Ana P Barreiros,
Stefan Lüth,
Carl C Schimanski,
Markus Schuchmann,
Andreas Schwarting,
Markus Neurath,
Gerd Otto,
Peter R Galle,
Ansgar W Lohse
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ABSTRACT: Prolonged persistence of donor-derived T cells after organ transplantation has been proposed to improve long-term allograft survival. However, surviving transplant-derived T cells are also able to mediate devastating graft-versus-host disease (GvHD). Currently, GvHD after organ transplantation is usually refractory to conventional therapy and the disease outcome fatal.
Graft-reactive host T cells were generated ex vivo from a patient suffering from a severe and refractory liver-transplant-associated GvHD. To control GvHD, activated alloreactive host T cells were repetitively retransferred into the patient (activated host lymphocyte infusion [aHLI]).
Adoptive transfer of ex vivo activated alloreactive host T cells (aHLI) led to the control and complete resolution of severe GvHD without inducing allograft rejection.
aHLI opens a novel therapeutic window to control solid-organ transplant-associated GvHD while preserving allograft integrity.
Transplantation 01/2005; 78(12):1774-9. · 4.00 Impact Factor
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ABSTRACT: Infection remains the major complication of immunosuppressive therapy in organ transplantation. Therefore, reconstitution of the innate immunity against infections, without activation of the adaptive immune responses, to prevent graft rejection is a clinically desirable status in transplant recipients. We found that GM-CSF restored TNF mRNA and protein expression without inducing IL-2 production and T cell proliferation in glucocorticoid-immunosuppressed blood from either healthy donors or liver transplant patients. Gene array experiments indicated that GM-CSF selectively restored a variety of dexamethasone-suppressed, LPS-inducible genes relevant for innate immunity. A possible explanation for the lack of GM-CSF to restore T cell proliferation is its enhancement of the release of IL-1betaR antagonist, rather than of IL-1beta itself, since exogenously added IL-1beta induced an IL-2-independent Con A-stimulated proliferation of glucocorticoid-immunosuppressed lymphocytes. Finally, to test the in vivo relevance of our findings, we showed that GM-CSF restored the survival of dexamethasone- or cyclosporine A-immunosuppressed mice from an otherwise lethal infection with Salmonella typhimurium. In addition to this increased resistance to infection, GM-CSF did not induce graft rejection of a skin allotransplant in cyclosporine A-immunosuppressed mice. The selective restoration potential of GM-CSF suggests its therapeutic use in improving the resistance against infections upon organ transplantation.
The Journal of Immunology 08/2003; 171(2):938-47. · 5.79 Impact Factor
