Helmut Muller

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.

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.

Noninvasive measurement of pulmonary vascular resistances by assessment of cardiac output and pulmonary transit time.

Müller HM, Tripolt MB, Rehak PH, et al. Noninvasive measurement of pulmonary vascular resistances by assessment of cardiac output and pulmonary transit time. Invest Radiol 2000;35:727–731. RATIONALE AND OBJECTIVES.Pulmonary vascular resistance is of special interest in many diseases. Usually it is determined invasively by catheterization, but cardiac output and pulmonary transit time can be ascertained by several noninvasive methods. METHODS.Fourteen heart recipients (age 34–71 years) were examined by electron-beam CT of the heart. Cine and flow studies were performed using a total of 60 mL of contrast and a breath-hold of 20 seconds. RESULTS.A mathematical model for calculating pulmonary vascular resistances from noninvasively measured cardiac outputs and pulmonary transit times was developed. Right-sided heart catheterization served as the reference method. CONCLUSIONS.The formula created seems to allow a clinically valid estimate of pulmonary vascular resistance from noninvasively acquired data.

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.

Testicular synthesis and vitamin D action.

CONTEXT The vitamin D system has pleiotropic effects not only in bone metabolism. Its role in testicular steroidogenesis is new and deserves intensive research. OBJECTIVE We hypothesize that vitamin D, especially 1,25 dihydroxyvitamin D3 [1,25(OH)2D3 (calcitriol)] induces male steroidogenesis and intend to identify its impact on genes and pathways in testicular androgen regulation. METHODS Human adult primary testicular cells were isolated, treated with 1,25(OH)2D3, and their gene expression levels profiled by microarray analysis. Highly regulated genes were confirmed by real-time quantitative PCR. In addition, the effects of 1,25(OH)2D3 in combination with LH and IGF-I on the gene expression level of androgens were assessed. T levels in the culture media were determined by a high-resolution ELISA. The expression of vitamin D receptor was confirmed at baseline and after 1,25(OH)2D3 stimulation using immunocytochemistry. RESULTS Microarrays depicted 63 genes significantly regulated by 1,25(OH)2D3, including genes related to male androgen and vitamin D metabolism, mainly triggered by the vitamin D receptor/retinoid X receptor activation. 1,25(OH)2D3 led to significant changes in the expression profiles of reproductive genes and significantly increased T synthesis in human testicular cell cultures. CONCLUSIONS Data from our human primary testicular cell culture model suggest that vitamin D plays a major role in male steroidogenesis in vitro.

The impact of overweight on the development of diabetes after heart transplantation.

Abstract:  Background:  Overweight is defined with a body mass index (BMI) >25. A BMI >25 is known as an independent risk factor for increased morbidity and mortality. The influence of an increased BMI on the development of diabetes and on survival after heart transplantation (HTX) was investigated.

Characteristics and clinical relevance of chronic anemia in adult heart transplant recipients

Background: Mild chronic anemia following heart transplantation (HTX), with hemoglobin (Hb) values of 10–14 g/dL in men and 10–12 g/dL in women, is frequent. It has continued to be of uncertain etiology yet clinical relevance. Nonetheless, therapeutic immunosuppression has been regarded as a major cause of chronic anemia in HTX patients. 
Methods: Sixty outpatients were observed over a period of 5 yr after HTX. Laboratory values related to anemia such as Hb, erythropoietin (EPO), ferritin, transferrin, iron, and vitamin levels were obtained and analyzed monthly. Patients were divided into two groups retrospectively. Patients with persistent anemia for more than 1 yr were compared with non‐anemic patients. 
Results: Forty‐three (72%) of the 60 patients were anemic. Anemia was normochromic, normocytic, and slightly anisocytic. Anemic and non‐anemic patients showed EPO levels within the expected range as defined by Erslev (Erythropoietin. N Engl J Med 1991: 324: 1339). Reticulocyte counts were found to be normal in all patients. Iron deficiency and deficiency of vitamin B12 or folic acid were not observed. Patients with persistent anemia showed a significantly shorter survival period than non‐anemic patients (p<0.02). 
Conclusions: Mild anemia following HTX shows the same characteristics as anemia in chronic diseases. Persisting mild anemia used to be associated with a shorter life expectancy. There is no evidence that standard immunosuppression causes anemia.

MicroRNAs 223-3p and 93-5p in patients with chronic kidney disease before and after renal transplantation.

Chronic kidney disease (CKD) is associated with a multifactorial dysregulation of bone and vascular calcification and closely linked to increased cardiovascular mortality and concomitant bone disease. We aimed to investigate specific microRNA (miRNA) signatures in CKD patients to find indicators for vascular calcification and/or bone mineralization changes during CKD and after kidney transplantation (KT). A miRNA array was used to investigate serum miRNA profiles in CKD patients, then selected miRNAs were quantified in a validation cohort comprising 73 patients in CKD stages 3 to 5, 67 CKD patients after KT, and 36 healthy controls. A spectrum of biochemical parameters including markers for kidney function, inflammation, glucose, and mineral metabolism was determined. The relative expression of miR-223-3p and miR-93-5p was down-regulated in patients with CKD stage 4 and 5 compared to healthy controls. This down-regulation disappeared after kidney transplantation even when lower glomerular filtration rates (eGFR) persisted. MiR-223-3p and miR-93-5p were associated with interleukin-6 (IL-6) and eGFR levels, and by trend with interleukin-8 (IL-8), C-peptide, hematocrit, and parathyroid hormone (PTH). This study contributes new knowledge of serum miRNA expression profiles in CKD, potentially reflecting pathophysiological changes of bone and calcification pathways associated with inflammation, vascular calcification, mineral and glucose metabolism. Identified miRNA signatures can contribute to future risk markers or future therapeutic targets in bone and kidney disease.

Measurement of cardiac output and pulmonary transit time for assessment of pulmonary vascular resistance in domestic piglets

The degree of elevated pulmonary vascular resistance (PVR) is a crucial clinical parameter. Cardiac output (CO) and pulmonary transit time (PTT) can be ascertained by a number of radiological methods. A close functional relationship between CO, PTT and PVR would facilitate non‐invasive PVR measurements. One‐hundred and fifty‐one measurements were made in six piglets. Pressures in the pulmonary and systemic circulation were measured invasively. Cardic output was determined by the use of a Doppler flow probe around the truncus pulmonalis. Temperature sensors were placed in the pulmonary truncus and left atrium. Elevated PVR was produced by repeated air embolism. After injection of ice‐cold saline, the time span between the minimal temperature in the truncus pulmonalis and the left atrium was taken as PTT. The CO and PTT were inserted into a new formula derived from the Hagen–Poiseuille law for the calculation of the PVR model. Numerical constants of the formula were calculated by the robust method of minimization. The PVR values, as calculated from invasively measured mean pulmonary artery pressure, mean left atrial pressure and CO, served as reference. In the six piglets, the PVR model and PVR reference showed a strong linear correlation with r= 0.923. The Bland–Altman plot revealed a standard deviation of −0.64/+0.67 Wood units. Cardiac output, PTT and PVR showed a close functional relationship. With a correction for blood viscosity and body size, this relationship could be used for non‐invasive clinical measurements of PVR.

Indications for liver transplantation in adults

SummaryLiver transplantation has emerged as an established and well-accepted therapeutic option for patients with acute and chronic liver failure and hepatocellular carcinoma. The disproportion between recipients and donors is still an ongoing problem that has only been solved partially over the last centuries. For several patients no life-saving organs can be distributed. Therefore, objective and internationally established recommendations regarding indication and organ allocation are imperative. The aim of this article is to establish evidence-based recommendations regarding the evaluation and assessment of adult candidates for liver transplantation. This publication is the first Austrian consensus paper issued and approved by the Austrian Society of Gastroenterology and Hepatology in cooperation with the Austrian Society of Transplantation, Infusion and Genetics.