Erik Bärthel

Sustained clearance of serum hepatitis C virus-RNA independently predicts long-term survival in liver transplant patients with recurrent hepatitis C.

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.

Antiviral maintenance treatment with interferon and ribavirin for recurrent hepatitis C after liver transplantation: pilot study.

Background:  The aim of this pilot study was to evaluate efficacy of a long‐term antiviral maintenance therapy (AMT) with interferon‐α2b and ribavirin in liver transplant recipients with recurrent hepatitis C.

Impact of stable PGI2 analog iloprost on early graft viability after liver transplantation: a pilot study

Bärthel E, Rauchfuß F, Hoyer H, Habrecht O, Jandt K, Götz M, Voigt R, Heise M, Marx G, Settmacher U. Impact of stable PGI2 analog iloprost on early graft viability after liver transplantation: a pilot study. 
Clin Transplant 2012: 26: E38–E47. 
© 2011 John Wiley & Sons A/S.

Living donor liver transplantation in adults in the MELD era in Germany – a multi‐center retrospective analysis

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’.

Conversion to mycophenolate mofetil for modulating recurrent hepatitis C in liver transplant recipients

Abstract: Background. The aim of this study was to analyze the influence of cyclosporine A (CsA) taper in conjunction with mycophenolate mofetil (MMF) therapy on recurrent hepatitis C virus (HCV) in liver transplant patients.

Antiviral treatment withdrawal in viremic HCV-positive liver transplant patients: impact on viral loads, allograft function and morphology

Abstract: Background: 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.

The PRAISE study: a prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749).

BackgroundLiver 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/DesignA 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.DiscussionA 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 RegistrationGerman Clinical Trials Register: DRKS00003514. Current Controlled Trials Register: ISRCTN12622749.

Combined en-bloc liver-pancreas transplantation in patients with liver cirrhosis and insulin-dependent type 2 diabetes mellitus.

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.

Adjuvant conversion to sirolimus in liver transplant patients with recurrent hepatocellular carcinoma – preliminary results

The adoption of the Milan criteria a decade ago has significantly improved the outcome of liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) [1]. The application of new techniques for pretransplant tumor ‘downsizing’ and ‘downstaging’, as well as the introduction of living donor LT with hence reduced time on the waiting list, has recently stimulated a controversy about the expansion of tumor burden limits [2–5]. The acceptance of extended HCC criteria in the transplant setup will very much depend on the prognosis of recipients suffering from recurrent HCC, as tumor recurrence is the major factor of mortality in this special patient population [6]. However, the therapeutic possibilities for immunocompromized LT patients with HCC recurrence are still very limited [7,8]. Against this background, the introduction of an immunosuppressant with antineoplastic activity might be inherently attractive. Sirolimus (SLR) is a macrocyclic triene antibiotic that was found to have potent immunosuppressive and antiproliferative capabilities, which may offer a new approach in the treatment of recurrent HCC post-LT [9]. We describe here our first experiences with an adjuvant conversion to an SRL-based immunosuppression in a cohort of liver recipients with HCC recurrence.

Current techniques for AB0-incompatible living donor liver transplantation

For a long time, it was considered medical malpractice to neglect the blood group system during transplantation. Because there are far more patients waiting for organs than organs available, a variety of attempts have been made to transplant AB0-incompatible (AB0i) grafts. Improvements in AB0i graft survival rates have been achieved with immunosuppression regimens and plasma treatment procedures. Nevertheless, some grafts are rejected early after AB0i living donor liver transplantation (LDLT) due to antibody mediated rejection or later biliary complications that affect the quality of life. Therefore, the AB0i LDLT is an option only for emergency situations, and it requires careful planning. This review compares the treatment possibilities and their effect on the patients’ graft outcome from 2010 to the present. We compared 11 transplant center regimens and their outcomes. The best improvement, next to plasma treatment procedures, has been reached with the prophylactic use of rituximab more than one week before AB0i LDLT. Unfortunately, no standardized treatment protocols are available. Each center treats its patients with its own scheme. Nevertheless, the transplant results are homogeneous. Due to refined treatment strategies, AB0i LDLT is a feasible option today and almost free of severe complications.