F. Iberer

Sirolimus has a potential to influent viral recurrence in HCV positive liver transplant candidates.

There is in vitro proof that mTOR proteins play a role in protecting HCV infected cells from apoptosis. The aim of this cohort study was to evaluate the effect of sirolimus as an mTOR inhibitor on hepatitis C recurrence in liver transplant recipients. Hepatitis C virus positive patients were followed prospectively regarding transaminases, immunosuppressive target levels, HCV RNA and influence of donor and recipient factors on viral recurrence and survival. Viral recurrence was defined as elevated liver enzymes combined with active hepatitis diagnosed on the basis of increasing viral load and/or biopsy-proven HCV relapse in the transplanted organ. Sixty-seven HCV positive patients were included: 39 received a regimen including sirolimus; 28 patients received calcineurin inhibitors. Sirolimus patients showed a significant decrease in the HCV PCR levels (p<0.05). Survival of the sirolimus patients was significantly higher (p<0.03) than in the other patient cohort. Sirolimus has been shown to be a potent immunosuppressive agent after liver transplantation, though nothing is known about its effect on HCV. This analysis suggests that sirolimus has potential to suppress viral recurrence in HCV positive liver transplant candidates.

Incisional hernia following liver transplantation: incidence and predisposing factors

Abstract:  Background:  Patients after orthotopic liver transplantation (OLT) have a high risk of developing incisional hernia (IH). In the literature incidences between 5% and 17% are reported.

Dyslipidemia during sirolimus therapy in patients after liver transplantation

Abstract:  Introduction:  Sirolimus (SRL) is an immunosuppressive agent of potential benefit in clinical liver transplantation (LTX). One of the major side effects of SRL is hyperlipidemia, which is reported in up to 44% of patients. In this report, we describe the lipid profiles of 20 stable liver transplant recipients who received SRL for immunosuppression.

Evaluation of indocyanine green clearance and model for end-stage liver disease for estimation of short-term prognosis in decompensated cirrhosis

Background: Indocyanine green (ICG) clearance has been proposed as a quantitative liver function test several decades ago. Interest in this method has been renewed following the development of finger pulse densitometry for noninvasive estimation of the ICG plasma disappearance rate (PDR). On the other hand, the model for end‐stage liver disease (MELD), which is based on routine laboratory parameters, is widely used for estimation of short‐term survival in cirrhosis, but its prognostic value in critically ill cirrhotic patients is unclear.

Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.

Wagner D, Adunka C, Kniepeiss D, Jakoby E, Schaffellner S, Kandlbauer M, Fahrleitner‐Pammer A, Roller RE, Kornprat P, Müller H, Iberer F, Tscheliessnigg KH. Serum albumin, subjective global assessment, body mass index and the bioimpedance analysis in the assessment of malnutrition in patients up to 15 years after liver transplantation.
Clin Transplant 2011: 25: E396–E3400.

Morphological and functional characterization of a pancreatic beta-cell line microencapsulated in sodium cellulose sulfate/poly(diallyldimethylammonium chloride).

Abstract:  Background:  Late diabetic complications cannot be prevented totally by current antidiabetic strategies. Therefore, new therapeutic concepts of insulin replacement such as pancreas transplantation are evolving. Due to the shortage of human donor organs, transplantation of microencapsulated xenogeneic pancreatic islet cells has attracted considerable attention. Sodium cellulose sulfate/poly(diallyldimethylammonium chloride) (NaCS/PDADMAC) is a material with favorable biogenic properties that has been used for microencapsulation of various cell types. However, there are no data on the suitability of NaCS/PDADMAC for microencapsulation of pancreatic β‐cells.

The assessment of GFR after orthotopic liver transplantation using cystatin C and creatinine‐based equations

The measurement of kidney function after orthotopic liver transplantation (OLT) is still a clinical challenge. Cystatin C (CysC) has been proposed as a more accurate marker of renal function than serum creatinine (sCr). The aim of this study was to evaluate sCr‐ and CysC‐based equations including the Chronic kidney disease (CKD)‐EPI to determine renal function in liver transplant recipients. CysC and sCr were measured in 49 patients 24 months after OLT. The glomerular filtration rate (GFR) was calculated using the MDRD 4, the Cockroft‐Gault, Hoek, Larsson, and the CKD‐EPI equations based on sCr and/or CysC. As reference method, inulin clearance (IC) was estimated. Bias, precision, and accuracy of each equation were assessed and compared with respect to IC. Forty‐five percent had a GFR < 60 ml/min/1.73 m2 according to the IC. The Larsson, the Hoek and the CKD‐EPI‐CysC formula identified the highest percentage of patients with CKD correctly (88%, 88%, and 84%, respectively). The sCr‐based equations showed less bias than CysC‐based formulas with a similar precision. All CysC‐based equations were superior as compared with sCr‐based equations in the assessment of renal function in patients with an IC < 60 ml/min/1.73 m2.

Oxidative stress and apoptosis in a pig model of brain death (BD) and living donation (LD)

BackgroundAs organ shortage is increasing, the acceptance of marginal donors increases, which might result in poor organ function and patient survival. Mostly, organ damage is caused during brain death (BD), cold ischemic time (CIT) or after reperfusion due to oxidative stress or the induction of apoptosis. The aim of this study was to study a panel of genes involved in oxidative stress and apoptosis and compare these findings with immunohistochemistry from a BD and living donation (LD) pig model and after cold ischemia time (CIT).MethodsBD was induced in pigs; after 12 h organ retrieval was performed; heart, liver and kidney tissue specimens were collected in the BD (n = 6) and in a LD model (n = 6). PCR analysis for NFKB1, GSS, SOD2, PPAR-alpha, OXSR1, BAX, BCL2L1, and HSP 70.2 was performed and immunohistochemistry used to show apoptosis and nitrosative stress induced cell damage.ResultsIn heart tissue of BD BAX, BCL2L1 and HSP 70.2 increased significantly after CIT. Only SOD2 was over-expressed after CIT in BD liver tissue. In kidney tissue, BCL2L1, NFKB, OXSR1, SOD2 and HSP 70.2 expression was significantly elevated in LD. Immunohistochemistry showed a significant increase in activated Caspase 3 and nitrotyrosine positive cells after CIT in BD in liver and in kidney tissue but not in heart tissue.ConclusionThe up-regulation of protective and apoptotic genes seems to be divergent in the different organs in the BD and LD setting; however, immunohistochemistry revealed more apoptotic and nitrotyrosine positive cells in the BD setting in liver and kidney tissue whereas in heart tissue both BD and LD showed an increase.

Intramyocardial Electrogram Variability in the Monitoring of Graft Rejection After Heart Transplantation

The ventricular evoked response is a well‐standardized electrophysiological signal that can be used for noninvasive, long‐term cardiac transplant monitoring. Rejection‐sensitive and infection‐specific parameters extracted from intramyocardial electrograms correlate with clinical results. The influences of pacing rate, transition from intrinsic to paced rhythm and positional changes on the diagnostic parameters were studied. Increasing the pacing rate shortened the ventricular evoked response and directly influenced the infection specific parameter. The rejection‐sensitive parameter remained stable at pacing rates between 100 and 120 beats/min. Measurements made immediately after the patient assumed a supine position and after switching to paced rhythm showed a decrease in the rejection‐sensitive parameter. A change in position from supine to upright did not influence the rejection‐sensitive parameter, but higher values were measured after returning to the supine position. In conclusion, noninvasive recordings of the ventricular evoked response for monitoring of cardiac allograft should be done at the same time of day, at the same pacing rate, and with the patient resting for at least 5 minutes before measurements are made.

Non-invasive cardiac allograft monitoring: the Graz experience

Based on previous reports by our group, initial studies on non-invasive cardiac graft monitoring have been presented recently. In this study we define new parameters to monitor rejection and infection after heart transplantation (HTX) the ventricular evoked response (VER) T-slew rate parameter is defined as the maximum negative slope in the descending part of the repolarization phase of the VER. We calculated the VER duration parameter in milliseconds and defined it as the time between the pacemaker spike and the cross-over of the baseline, with the slope line used to calculate the VER T-slew rate. During the HTX procedure, we implant wide-band telemetric pacemakers and fractally coated, epimyocardial electrodes (Physios CTM 01 and ELC 54-UP, Biotronik; Berlin, Germany). During each follow-up and on biopsy days, intramyocardial electrogram sequences were obtained and sent via the Internet to the central data-processing unit in Graz. We scored the infection status of the patients before data acquisition. The VER parameters were automatically calculated and send back within a few minutes. We prospectivly compared 1,613 follow-ups from 42 patients with biopsy (International Society of Heart and Lung Transplantation grading) and infection classification. The VER duration parameter did not change during rejection; however, we found an increase during clinically apparent infection. The VER T-slew rate parameter was lower during rejection grade 2 or higher, as well as during clinically apparent infection. The negative predictive value to rule out rejection was 99%. Our results indicate that rejection and infection cause different, reproducible effects on the electrical activity of the transplanted heart. Non-invasive cardiac graft monitoring may reduce the need for surveillance biopsies and may offer a tool to optimize immunosuppressive therapy after HTX.