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ABSTRACT: BACKGROUND: Liver graft dysfunction can deteriorate to complete organ failure and increases perioperative morbidity and mortality after liver transplantation. Therapeutic strategies reducing the rate of graft dysfunction are of current clinical relevance. One approach is the systemic application of prostaglandins, which were demonstrated to be beneficial in reducing ischemia-reperfusion injury. Preliminary data indicate a positive effect of prostacyclin analogue iloprost on allograft viability after liver transplantation. The objective of the study is to evaluate the impact of iloprost in a multi-center trial. METHODS: A prospective, double-blinded, randomized, placebo-controlled multicenter study in a total of 365 liver transplant recipients was designed to assess the effect of intravenous iloprost after liver transplantation. Primary endpoint will be the primary graft dysfunction characterized as presentation of one or more of the following criteria: ALAT or ASAT level > 2000 IU/ml within the first 7 postoperative days, bilirubine >= 10 mg/dl on postoperative day 7; INR >= 1.6 on postoperative day 7 or initial non-function. Secondary endpoints are parameters of post-transplant morbidity, like rates of infections, biliary complications, need of clotting factors or renal replacement therapy and the graft and patient survival. DISCUSSION: A well-established treatment concept to avoid graft dysfunction after liver transplantation does not exist at the moment. If the data of this research project confirm prior findings, iloprost would improve the general outcome after liver transplantation.Trial Registration: German Clinical Trials Register: DRKS00003514. Current Controlled Trials Register: ISRCTN12622749.
BMC Surgery 01/2013; 13(1):1. · 1.33 Impact Factor
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ABSTRACT: Ischemia/reperfusion injury after liver transplantation (LT) may be associated with primary graft dysfunction (PDF) or non-function. Prostaglandins were demonstrated to be beneficial in reducing ischemic injury by improving microcirculation and protecting endothelial cells. The aim of this study was to analyze the effect of the continuously administered prostaglandin I(2) analog iloprost on allograft function after LT.
Eighty patients were prospectively randomized and assigned to two groups. Patients in the treatment group received iloprost for seven d after transplantation, and those in the control group did not. The primary end point was graft dysfunction.
The incidence of PDF was 20% (n = 8) in the control group and 5% (n = 2) in the treatment group, respectively (p = 0.087). Four patients in the control group underwent re-transplantation for initial non-function (INF). There was no evidence for INF in the treatment group. Iloprost was associated with improved allograft function. Clinical course and outcome were comparable.
We suggest iloprost to be beneficial for early post-transplant liver function. If the rate of PDF can be significantly reduced with this treatment concept, it should be analyzed in a larger number of patients (ISRCTN95672167).
Clinical Transplantation 09/2011; 26(1):E38-47. · 1.67 Impact Factor
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Utz Settmacher,
Max Götz,
Axel Rahmel, Erik Bärthel,
Hans Schlitt,
Gero Puhl,
Dieter Broering,
Frank Lehner,
Lutz Fischer,
Andreas Paul,
Jan Schmidt,
Silvio Nadalin,
Aiman Obed,
Michael Heise
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ABSTRACT: The aim of this analysis was to provide an update on the current trend in living donor liver transplantation (LDLT) for adult recipients in the model of end stage liver disease (MELD) era in Germany and to encourage a wider implementation of LDLT. We descriptively analysed the data of LDLTs in Germany from 15 December 2006 to 31 December 2009 using a multi-center retrospective analysis via a questionnaire and data provided by Eurotransplant. Ten German centers performed LDLTs in adults. Eighty four transplantations in 50 male recipients and 34 female recipients were performed during the review period, ranging from 1 to 16 LDLTs per center. Hepatocellular carcinoma in cirrhosis (15/84) was the most common transplantation indication. The recipient mean lab-MELD score was 15 (±8). Six re-transplantations were necessary after initial LDLTs. The 1-year patient survival was 81%. We obtained data of 79/84 donors. The incidence of complications was 30.4% (n = 24). There were no grade 5 complications according to the Clavien classification. LDLT is an established treatment option that may reduce the waiting time, provides high quality split liver grafts and should be advocated in the MELD era to reduce organ shortage and 'death on the waiting list'.
Transplant International 06/2011; 24(9):904-11. · 2.92 Impact Factor
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ABSTRACT: We report about our experience with combined en-bloc liver-pancreas transplantation in 14 patients with liver cirrhosis and insulin dependent type 2 diabetes mellitus. Exocrine drainage was achieved by duodeno-duodenostomy. Median posttransplant follow-up is currently 92.5 months. All patients were rendered independent from insulin therapy shortly after transplantation. Levels of glycosylated hemoglobin normalized in all recipients. Mean fasting C-peptide values increased from pretransplant 7.0+/-1.7 ng/mL to 10.5+/-2.9 ng/mL 3 months posttransplantation (P<0.001). One recipient (7.1%) developed recurrent exogenous insulin dependence 7 years after transplantation. Pancreas allograft rejection was confirmed by endoscopic biopsy of donor duodenum mucosa in two patients (14.3%). Calculated 5- and 7-year survival is currently at 64.3% and 64.3%, respectively. Our results indicate that combined en-bloc liver-pancreas transplantation using duodeno-duodenostomy is technically feasible and leads to excellent long-term control of glucose metabolism in patients with liver cirrhosis and insulin-dependent type 2 diabetes.
Transplantation 03/2009; 87(4):542-5. · 4.00 Impact Factor
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ABSTRACT: The aim of this study was to analyze the impact of virological response to long-term antiviral therapy using interferon plus ribavirin on survival of 30 liver transplant patients with recurrent hepatitis C. Mean treatment duration is currently 46 months (range: 3-144 months). Sustained clearance of serum hepatitis C virus RNA was achieved in 18 patients (60%). Allograft biopsies demonstrated fibrosis progression in seven virological nonresponders (66.6%), and none of the recipients with viral elimination (0%; P<0.001). Univariately, low pretransplant viral loads, the absence of cytomegalovirus infection, as well as biochemical and virological response to antiviral therapy indicated a positive impact on outcome (P<0.05). Only antiviral treatment induced clearance of viremia, however, was identified as independent predictor of long-term survival (P=0.02). Our data indicate that an antiviral combination should aim at viral eradication in liver transplant patients with recurrent hepatitis C, because it improves survival.
Transplantation 08/2008; 86(3):469-73. · 4.00 Impact Factor
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ABSTRACT: The aim of this pilot study was to evaluate efficacy of a long-term antiviral maintenance therapy (AMT) with interferon-alpha2b and ribavirin in liver transplant recipients with recurrent hepatitis C.
Twenty-one patients with recurrent hepatitis C after liver transplantation received AMT with interferon and ribavirin, following 12 months of a basic antiviral combination treatment. Allograft function, viremia loads and allograft morphology were evaluated continuously.
After 12 months of basic antiviral therapy, 14 patients (66.6%) had achieved initial clearance of viremia levels, and 17 recipients (81%) demonstrated normalization of allograft function, respectively. Inflammation score declined significantly (6.0 vs 3.9; P = 0.002), while stage of fibrosis remained unchanged. In virological responders maintenance therapy led to further regression of inflammation score (4.0 at baseline vs 3.1 at 24 months AMT) and fibrosis score (1.6 at baseline vs 1.1 at 24 months AMT). Despite persistence of viremia levels, continued antiviral therapy prevented progression to severe allograft inflammation in virological non-responders. Hematologic adverse effects resulted in treatment discontinuation in seven patients (33.3%).
Long-term AMT, if tolerable, might be an effective approach for preventing progression to severe allograft fibrosis and thereby improving long-term survival in liver transplant recipients with recurrent hepatitis C.
Journal of Gastroenterology and Hepatology 01/2008; 22(12):2135-42. · 2.87 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the clinical long-term consequences of antiviral treatment discontinuation in viremic hepatitis C virus (HCV)-positive liver transplant recipients.
Twenty-five HCV-positive patients after liver transplantation were included in this study. After diagnosing recurrent hepatitis C, a combination therapy with interferon-alpha2b and ribavirin for a minimum of 12 months was initiated. Viremia levels and allograft function were monitored continuously. Allograft biopsies were performed yearly, analyzing grading of inflammation and staging of fibrosis.
HCV recurrence rate was 100%. Up to 114 months post-transplantation, sustained virological response rate was 64%. Treatment discontinuation in virological nonresponders led subsequently to a significant increase of viral loads and deterioration of allograft function (P<0.05) within 1 month. In three patients, a fibrosing cholestatic syndrome developed, resulting in one patient death. Antiviral retherapy was maintained for a mean of 33 months, leading to a significant decline of aminotransferases (P<0.05) as well as decreasing serum levels of bilirubin and HCV-RNA within 6 months. In addition, development of severe allograft fibrosis was prevented despite persistent viral loads.
Our study suggests that antiviral treatment withdrawal carries the risk of severe disease progression in persistently viremic HCV-positive liver transplant patients.
Liver international: official journal of the International Association for the Study of the Liver 09/2006; 26(7):811-6. · 3.82 Impact Factor
