Bioprosthetic valve thrombosis and degeneration following transcatheter aortic valve implantation (TAVI).

Bioprosthetic valve thrombosis (BPVT) is a recognised complication of prosthetic aortic valves and can be found in up to 13% of patients after transcatheter implantation. The mechanism of BPVT is not well known, abnormal flow conditions in the new and native sinuses and lack of functional endothelialisation are suspected causes. BPVT may result in valve dysfunction, possibly related to degeneration, and recurrence of patient symptoms, or remain subclinical. BPVT is best diagnosed at multiphase gated computed tomography (CT) angiography as the presence of reduced leaflet motion (RELM) and hypoattenuating aortic leaflet thickening (HALT). Although CT is used to exclude BPVT in symptomatic patients and those with increased valve gradients, the value of screening and prophylactic anticoagulation is debatable.

Abdominal Compartment Syndrome After Liver Transplant in Drug-Induced Acute Liver Failure: A Case Report.

The incidence of drug-induced acute liver failure (ALF) has been increasing in recent years. Despite the complex intensive treatment, liver transplant should be performed in progressive cases. A systemic inflammatory response syndrome and the burden of surgical intervention promote abdominal compartment syndrome (ACS); observed preoperatively, they are significant negative prognostic factors. THE CASE: We demonstrate a young woman with liver transplant after ALF and a consecutive ACS. We presumed drug toxicity in the background of the rapidly progressive ALF, based on the preoperative hematologic examination and the histology of the removed liver. An ACS has occurred in the postoperative period that must have been resolved with mesh, and later, anatomic segment 2-3 resection had to be performed to further decrease the pressure. The patient left the hospital after 62 days with good graft function. DISCUSSION: A complex intensive care is mandatory in the case of orthotopic liver transplant for ALF. Outcomes are good after orthotopic liver transplant. An ACS might occur after surgery. In these rare cases a delayed abdominal closure or even a liver resection can be the only solution and sometimes an urgent need to resolve the life-threatening problem.

Management of Portal Hypertension After Liver Transplantation.

INTRODUCTION: Post-transplantation portal hypertension has severe complications, such as esophageal varix bleeding, therapy refractory ascites, extreme splenomegaly, and graft dysfunction. The aim of our study was to analyze the effectiveness of the therapeutic strategies and how to visualize the procedure. METHODS: A retrospective study involving liver transplantation patients from the Semmelweis University Department of Transplantation and Surgery was performed between 2005 and 2015. The prevalence, etiology, and leading complications of the condition were determined. The applied interventions' effects on the patients' ascites volume, splenic volume, and the occurrence of variceal bleeding were determined. Mean portal blood flow velocity and congestion index values were calculated using Doppler ultrasonography. RESULTS: The prevalence of post-transplantation portal hypertension requiring intervention was 2.8%. The most common etiology of the disease was portal anastomotic stenosis. The most common complications were esophageal varix bleeding and therapy refractory ascites. The patients' ascites volume decreased significantly (2923.3 ± 1893.2 mL vs. 423.3 ± 634.3 mL; P < .05), their splenic volume decreased markedly. After the interventions, only one case of recurrent variceal bleeding was reported. The calculated Doppler parameters were altered in the opposite direction in cases of pre-hepatic versus intra- or post-hepatic portal hypertension. After the interventions, these parameters shifted towards the physiologic ranges. CONCLUSION: The interventions performed in our clinic were effective in most cases. The patients' ascites volume, splenic volume, and the prevalence of variceal bleeding decreased after the treatment. Doppler ultrasonography has proved to be a valuable imaging modality in the diagnosis and the follow-up of post-transplantation portal hypertension.

Examinations of Factors Influencing Survival of Liver Transplantation for Hepatocellular Carcinoma: A Single-Center Experience From Budapest.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Orthotopic liver transplantation (OLT) is the best therapy of choice for early, unresectable HCC. The Hungarian Liver Transplantation Program was launched in 1995 at the Department of Transplantation and Surgery, Semmelweis University, Budapest. From that time more than 60 patients underwent OLT for hepatic tumors, which in most cases were HCC. Our clinical examination was undertaken to analyze the possible influential factors of outcomes for our series of patients who received OLT for HCC. METHODS: We performed a review of all patients who underwent OLT for HCC at our department from 1996 to October 1, 2013. Disease extent was determined by preoperative computed tomography or magnetic resonance images. All explants were examined and categorized based on tumor number, size, distribution, HCC histologic grade, and vascular invasion. Patients with HCC were classified as having tumors either meeting Milan criteria, beyond Milan criteria but within UCSF criteria, or exceeding UCSF criteria. OLT was performed using standard techniques including orthotopic implantation with cross-clamp technique or with the piggyback technique. Postoperative immunosuppression included a triple drug regimen of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and prednisone. mTOR inhibitors have been available since 2004. RESULTS: HCC most commonly occurs in the presence of cirrhosis as a result of longstanding chronic liver disease. Most of our patients who underwent OLT for HCC are 56 to 60 years old, and most also had underlying HCV cirrhosis. As of October 1, 2013, 21 of 49 (42.85%) patients had died after OLT for HCC. The main cause was the recurrence of the HCC in 38%, followed by sepsis in 33%, and HCV recurrence in 19%. One death each (4.7% of the total number of deaths) was caused by primary nonfunction of the graft, acute myocardial infarct, and de novo malignancy, respectively. Overall survival for the entire group at 1, 3, and 5 years after transplantation was 73.48%, 65.2%, and 50.08%, respectively. Using pretransplant imaging, 34 tumors (69.3%) were within Milan criteria, 8 (16.3%) were beyond Milan but within UCSF criteria, and 7 (14.3%) exceeded UCSF criteria. Based on explant pathology, 30 tumors (61.2%) were within Milan criteria, 7 (14,3%) were beyond Milan but within UCSF criteria, and 12 (24.3%) exceeded UCSF criteria. New onset, non-HCC malignant tumor developed in 2 cases (4%). There was no significant difference between the surgical techniques or the immunosuppressive strategies. Using the Cox analysis in our series, it can be seen that mortality was higher with tumors exceeding Milan criteria but within UCSF criteria compared with tumors within Milan criteria (Coef. = 0.5749 in Setting 1 and 0.1226 in Setting 2), and even higher with tumors beyond UCSF criteria compared with tumors within Milan criteria (Coef. = 0.7228 in Setting 1 and 0.1456 in Setting 2). Recurrence of the tumor causes higher mortality (Coef. = 1.709 in Setting 1 and 1.0256 in Setting 2). It seems that using an mTOR inhibitor has a beneficial impact on mortality (Coef. = -1.409 in Setting 1). Vascular invasion was associated with higher mortality (Coef. = 0.6581in Setting 1). Higher AFP levels correlated with higher mortality but not significantly (Coef. = 0.0002 in Setting 2). In our series, survival after OLT for HCC was best with tumors within Milan criteria comparing those exceeded Milan criteria (odds ratio = 4.000). CONCLUSION: According to our findings, the Milan criteria are still the safest criteria system; however, slightly expanded criteria do not have significantly worse results. Preoperative imaging methods sometimes show fewer or smaller tumors, and the explant histology reports the exact staging of HCC at the time of OLT. Histological examination especially of the lymphovascular invasion is mandatory to assess the estimated prognosis. Extremely high levels of AFP mean higher risk. HCC recurrence is an important factor on the outcome; therefore, continuous oncologic screening is mandatory. Immunosuppressant agents are chiefly responsible not just for higher risk of recurrence but for higher risk to develop de novo malignancies. Viral serology must be done periodically to catch HCV recurrence in time and begin adequate antiviral therapy. Potentially, mTOR inhibitors could be potent immunosuppressive agents after OLT for HCC due to this antiproliferative effect.

Analysis of Incretin Hormones After Orthotopic Liver Transplantation.

BACKGROUND: Several well-known risk factors play an important role in the development of new-onset diabetes mellitus after orthotopic liver transplantation (OLT). Immunosuppressant drugs and hepatitis C virus (HCV) infection have a direct effect on pancreatic beta cells resulting insulin hyposecretion. Steroids mainly cause peripheral insulin resistance. Although in type 2 diabetes mellitus the incretin-insulin axis is impaired and incretin hormones are advantageous targets of many antidiabetic drugs, the endocrinologic background of new-onset diabetes mellitus after transplantation (NODAT) is still not completely understood. METHODS: During the first postoperative year the oral glucose tolerance test (OGTT) was performed on 21 patients after OLT. Patients' glycemic metabolic status was determined according to the results of OGTT. The level of incretin hormones, namely glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), were measured with competitive enzyme-linked immunoassay reaction. RESULTS: Six patients had normal glucose tolerance (NGT), 9 had impaired glucose tolerance (IGT, serum glucose 7.8-11.0 mmol/L), and 6 were diagnosed with NODAT (serum glucose >11.1 mmol/L). Fasting insulin and c-peptide levels were higher if IGT/NODAT was found. Insulin secretion was not further stimulated after OGTT. GIP and GLP-1 levels did not differ significantly, not even after glucose load. HCV infection had not influenced the levels of incretin hormones [GLP-1 (0 min): 1.21 ± 0.27 vs 1.38 ± 0.65; P = ns; GLP-1 (120 min): 1.46 ± 0.61 vs 1.07 ± 0.58; P = ns; GIP (0 min): 2.55 ± 0.95 vs 1.99 ± 0.63; P = ns, GIP (120 min): 2.62 ± 0.6 vs 2.33 ± 0.77; P = ns]. CONCLUSION: The stimulation of insulin secretion in NODAT is limited. Incretin hormones are present independently from the current glycemic status. The use of dipeptidyl peptidase-4 inhibitors through their positive effect on the incretin-insulin axis can be beneficial in the therapy of NODAT after liver transplantation.

Endogenous thrombin potential and examination of a further 31 analytes in liver transplant candidates.

BACKGROUND: To predict the change in patient status and differentation of the basic diseases, endogenous thrombin potential (ETP), clinical chemistry, and coagulation variables were measured in liver transplant-listed patients with different etiologies. METHODS: Differences in values of ETP and analytes of 30 control persons and 164 cirrhotic patients were examined by means of binary logistic regression. The relationship between the analytes and ETP parameters were analyzed by means of Spearman correlation. The different etiologies of cirrhosises were studied by factor and discriminant analyses. Binary logistic regression was applied to forecast changes in clinical status. Survival analysis was carried out with the appropriate variable. RESULTS: International Normalized Ratio and activated partial thromboplastin time values were higher, whereas the area-under-the-curve values were lower in cirrhosis than in healthy subjects. A strong relationship was found only between the peak height and the anti-thrombin III (ATIII) values. In the factor analysis, 3 factors were found, which explained 81.6% of the total variance. Combination of aspartate aminotransferase and ATIII mostly separated the basic disease groups from each other in the discriminant analysis. From 35 variables, the lactate dehydrogenase (LDH) and ATIII have been suited for predicting the change in patient status. Eighty percent of patients with low ATIII and high LDH levels had deterioration of their clinical status. CONCLUSIONS: Our study demonstrated that the ETP parameters did not provide additional information compared with "conventional" coagulation tests in cirrhosis. On the basis of our study, LDH and ATIII appear to be promising analytes to assess the clinical status of patients with cirrhosis. In our opinion, the classification system of liver transplant-listed patients can be improved with their use.

New-onset diabetes mellitus and the analysis of dipeptidyl-peptidase-4 after liver transplantation.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a common complication after orthotopic liver transplantation (OLT). The diabetogenic effect of hepatitis C virus (HCV) infection is well known. The aim of this study was to analyze the glucose homeostasis before and after OLT. The oral glucose tolerance test (OGTT) was carried out, and dipeptidyl-peptidase-4 (DPP-4) activity was measured. METHODS: The study period was from 2012 to 2014. We enrolled 49 non-diabetic patients from the waiting list (group A) and 21 patients after OLT (group B). Seven patients were monitored continuously both before and after OLT. According to our preoperative OGTT results, 13 patients in group A had newly diagnosed diabetes mellitus (group A/DM) and 11 had impaired glucose tolerance (group A/IGT). In 25 cases, normal glucose tolerance was diagnosed (group A/NGT). The calculated homeostasis model assessment insulin resistance (HOMA2-IR) values were both in group A/DM and-IGT higher compared with group A/NGT (2.42 ± 0.81 vs 2 ± 0.98 vs 1.28 ± 0.67; P = .001). In the case of HCV infection (n = 14; 29%) DM and IGT were more frequent. RESULTS: Six patients in group B had NODAT. In 9 cases, IGT and in 6 cases NGT was detected. In the case of HCV infection (n = 9; 43%), DPP-4 levels were higher compared with that in patients with all other indications for OLT (15.5 ± 5.2 vs 8.7 ± 3.5; P = .008). We evaluated the same individuals before and after OLT (n = 7), and a decrease in ß-cell function was noted. CONCLUSIONS: Preoperative OGTT is an important and easy investigation to rule out glucose imbalance before OLT. The HOMA2 calculation can also be useful both in preoperative and postoperative risk assessment. In our results, DPP-4 activity is not specific for the type of glucose homeostasis imbalance, but, in HCV infection, it is higher. DPP-4 inhibitors can be effective in the therapy of NODAT, especially in HCV-infected patients.

Global Thrombosis Test (GTT) can detect major determinants of haemostasis including platelet reactivity, endogenous fibrinolytic and thrombin generating potential.

BACKGROUND: Detection of both thrombosis and bleeding risk are essential in clinical cardiology. Thrombin generated by activated platelets and from the extrinsic coagulation pathway is the major determinant of thrombogenesis and hemostasis. Although novel oral anticoagulants further increase the bleeding risk of antiplatelet drugs, platelet function tests do not reliably predict hemorrhagic complications. It seems that in addition to platelet aggregation, true assessment of bleeding risks requires the measurement of both platelet and plasma derived thrombin activity. OBJECTIVE: To adapt a novel, near-patient test for the assessment of both antithrombotic and anticoagulant effects of oral thrombin inhibitors. METHODS: The point-of-care Global Thrombosis Test (GTT), which measures platelet reactivity to shear-activation in native blood, was used. Thrombin, generated from activated platelets (procoagulant activity) plays a pivotal role in GTT measurement. In order to assess endogenous thrombin potential, in a separate blood sample thrombin generation was induced by microparticles formed during hypotonic hemolysis. Thus two blood samples were tested to measure simultaneously platelet reactivity (occlusion time, OT) and hemolysis (microparticles)-induced endogenous thrombin potential (OT-H). RESULTS: In healthy subjects (n=32), OT measured in native blood was reduced in hemolysed blood (100% vs. 43 ± 4%; OT vs. OT-H respectively). Shortening of OT in hemolysed blood (OT-H) was dose-dependently inhibited by the in vitro added thrombin inhibitor argatroban. In patients receiving dabigatran (n=27), OT and, to a lesser extent, OT-H was prolonged, compared to healthy volunteers. Intra-assay variation of OT-H was low (4.5%), but interindividual variation was great, both in healthy subjects (61%) and in patients on dabigatran (65%). Thrombin inhibitors argatroban, heparin (in vitro) and dabigatran (in vivo) all prolonged both OT and OT-H. There was no correlation between the measured OT and OT-H data. CONCLUSIONS: Microparticles shed from erythrocytes during hypotonic lysis of native blood considerably shortened OT. In a direct proportion to the applied concentrations, various thrombin inhibitors prolonged both OT (antithrombotic effect) and to a lesser extent, OT-H (anticoagulant effect). Further large studies are required to evaluate the usefulness of this technique in a clinical setting, in assessing the anticoagulant and antithrombotic effects of medication and relating GTT results with observed thrombotic and bleeding events.

PAR-1 antagonist vorapaxar favorably improves global thrombotic status in patients with coronary disease.

To assess the effect of vorapaxar on global thrombotic and thrombolytic status. The propensity for thrombus formation is determined by the balance between prothrombotic factors and endogenous thrombolysis. Impaired thrombolytic status increases cardiovascular risk. Vorapaxar is a novel, oral, protease-activated receptor-1 antagonist that inhibits thrombin-induced platelet activation. In the TRACER and TRA 2°P-TIMI 50 studies, patients with acute coronary syndromes and established atherosclerosis were randomized to vorapaxar 2.5 mg daily or placebo, in addition to standard care. In 57 patients enrolled in a single center, blood was tested with the point-of-care global thrombosis test, on and off treatment. This automated test employs non-anticoagulated blood to assess thrombotic and thrombolytic status, measuring the time required to form a shear-induced thrombus under physiological conditions (occlusion time, OT), and subsequently, the time to achieve endogenous lysis of the thrombus (lysis time, LT). Patients on vorapaxar exhibited longer OT on vs. off treatment [median 561 s (interquartile range 422-654) vs. 372 s(338-454), P = 0.003] and shorter LT on treatment than off [1,158 s(746-1,492) vs. 1,733 s(1,388-2,230), P = 0.016]. Patients on placebo showed no difference in OT [419 s(343-514) vs. 411 s(346-535), P = 0.658] or LT [1,236 s(985-1,594) vs. 1,400 s(1,092-1,686), P = 0.524] on and off treatment. During treatment, OT was longer in patients taking vorapaxar [561 s(422-654) vs. 419 s(343-514), P = 0.009], but LT was similar in vorapaxar and placebo arms [1,158 s(746-1,492) vs. 1,236 s(985-1,594), P = 0.277]. Vorapaxar prolongs OT and shortens LT, with favorable effects on thrombotic and thrombolytic status. In addition to its antiplatelet effect, vorapaxar may enhance endogenous thrombolysis, which is frequently impaired in coronary disease.

Retransplantations in the Hungarian liver transplant program.

Retransplantation of the liver (ReOLT), not infrequent consequence of transplantation, was analyzed from 512 patient records between 1995 and 2012. The 34 cases (33 secondary and 1 tertiary). Of ReOLT all employed cadaveric donor organs. The 34 reOLT were performed in 31 adults and 3 children. The original indication for OLT, among these patients was usually primary sclerosing cholangitis (PSC) and acute liver failure (ALF): there were no alcoholic liver disease (ALD) patients. The indication for early reOLT (within 3 months) was hepatic artery thrombosis while the late reOLTs beyond 3 months after primary transplantation was nonanastomotic biliary stenosis. The cumulative patient versus graft survivals were 61%, 52%, and 52% versus 61%, 52%, and 52% in contrast with primary OLT rates of 81%, 75%, and 70% versus 79%, 72%, and 61% respectively at (P = .03). In conclusion, our data suggested that the characteristics and number of early reOLTs did not change over time. However, the rate of late reOLTs increased. This can be explained by the increased rate of late onset biliary complications in spite of proper interventional radiological treatment. The second conclusion is that hepatitis C virus (HCV) recurrence did not become a main indication among late reOLT. Since a center policy states that patients with an early, cholestatic HCV recurrence are not referred for a secondary transplantation.

Technical risk factors for hepatic artery thrombosis after orthotopic liver transplantation: the Hungarian experience.

Hepatic artery thrombosis (HAT) significantly affects graft loss and mortality after orthotopic liver transplantation (OLT). The aim of this study was to analyze the risk factors of HAT in our program, with special regard to the personal-technical factor. We retrospectively analyzed the data of 500 adult liver transplant recipients between 1995 and 2011. Operations were performed by a certain group of surgeons, with standardized technique. The incidence rate of HAT decreased since 1995 from 12% to 7.8%. In accordance with the literature, HAT associated with acute rejection, polytransfusion, and the duration of the hepatectomy, arterial variations/reconstructions, tiny arteries, and furthermore, the timing of the anastomosis in Hungary. However we did not find an association with other parameters, like cytomegalovirus infection, and hepatocellular carcinoma as indication. We created a "difficulty index" that consists of the technical parameters. The difficulty index together with surgical experience (number of OLTs performed) had an outstanding association with HAT. In conclusion, the incidence and risk factors for HAT are similar to the results published by others. However, personal factors, such as experience, timing, given anatomy, and tiredness, might also play a significant role in the occurrence of HAT.

Biliary complications after orthotopic liver transplantation: the Hungarian experience.

Biliary complications (BC) significantly affect morbidity and mortality after orthotopic liver transplantation (OLT). The aim of this study was to analyze the incidence and types of biliary complications after OLT in Hungary. We retrospectively analyzed data of 471 adult liver transplant recipients between 1995 and 2011. Biliary complications occurred in 28% of patients. The most frequent BCs were bile duct stricture, stenosis (19%), biliary leakage (12%), and necrosis (BN: 6.4%). Biliary complications were associated with the incidence of acute rejection (51% vs 31%; P = .003), hepatic artery thrombosis (43% vs 11%; P < .001), and hepatic artery stenosis (26% vs 11%; P = .002). When cold ischemic time was longer than 12 hours, leakage (10% vs 3%; P = .043), ischemic type biliary lesion (20% vs 3.4%; P = .05), and BN (12% vs 3%; P = .067) were more often diagnosed post-OLT. Most of the biliary complications were treated by radiologic interventions (70%). Bile duct necrosis was associated with lower graft and patient survival. In conclusion, acute rejection, hepatic artery thrombosis/stenosis and cold ischemic time longer than 12 hours increase the incidence of BCs. Successful management of these risk factors can reduce the incidence of biliary complications and improve mortality.

Measurement and clinical significance of interleukin 28B in hepatitis C virus-infected liver transplant patients.

One-third of the liver transplantations are performed because of hepatitis C cirrhosis all over the world and also in Hungary. The recurrence rate is practically 100%, influencing graft and patient survivals; within 5 years cirrhosis develops again in 20% to 30% of cases. The therapy is pegylated interferon α-2a and α-2b plus ribavirin as for nontransplanted subjects with the goal to eradicate the virus and maintain graft function. In 25% to 45% of treated patients, it is possible to achieve a sustained virological response (SVR). The response is influenced by viral, donor, and recipient factors. We investigated the genotype of 68 liver recipients transplanted because of hepatitis C virus (HCV) infection between September 1998 and February 2011. We focused on the interleukin (IL) 28B gene locus single nucleotide polymorphism found on chromosome 19; the rs12979860 minor allele (homozygous [wild TT and CC], heterozygous [CT]) in relation to the interferon response. Ten percent of the patients belonged to the CC, 62% to the CT, and 28% to the TT group, and 83% of the CC group became negative or therapy is still ongoing. The CT genotype reached 15.4% SVR with ongoing treatment for most patients. In TT carriers showed a 23.5% SVR. Our patients formed a homogenous group regarding the surgical team, the therapy, and the HCV genotype. Ninety percent belonged to the possible "hard to treat" group. The 10% CC group gave the highest number of SVR and HCV polymerase chain reaction negativity upon antiviral therapy. Regarding our results, one has to take in consideration the small patient number and the fact that the cirrhotic patients were listed for transplantation where they could not be treated or became therapy-resistant. IL28B is just one predictive factor among others for successful posttransplant HCV therapy; further examinations are needed to fully understand its role.

Significance of mycophenolate monitoring in liver transplant recipients: toward the cut-off level.

Mycophenolate mofetil blocks the "de novo" -purine synthesis to reduce the incidence and severity of acute rejection episodes. There has been an increased interest in utility of monitoring mycophenolic acid (MPA) levels, however currently the MPA monitoring is not part of the protocol following liver transplantation. We assessed whether trough MPA monitoring could be advisable in liver transplant patients or not. For this reason MPA levels of 56 liver transplants were measured on 3, 5, 10, 14, 21, 30, 60, and 180 posttransplant days. The optimal cut-off of MPA level (≥1.73 mg/L) for all (56) and ≥1.34 mg/L for ciclosporin-treated- and ≥1.98 mg/L for the tacrolimus-treated transplants were calculated by statistical analysis to reduce the incidence of acute rejection. MPA concentrations of 3 days period before the day of clinical diagnosis acute rejection were well below the cut-off value. Only 3 (16%) out 19 patients with acute rejection had higher MPA levels than the cut-off value on the day of diagnosis of acute rejection. In conclusion, our data suggests that MPA predose level monitoring, especially in the early "filling phase" after transplantation, is applicable in liver allograft recipients given adjunctive MMF, protecting them from the ineffective immunosuppression.

Cytomegalovirus seroprevalence among solid organ donors in Hungary: correlations with age, gender, and blood group.

BACKGROUND: Cytomegalovirus (CMV) is endemic throughout the world, affecting most of the population, but the seroprevalence of CMV is known to vary among countries. CMV causes a mild infection in persons with intact immunity; however, CMV infection in organ transplantation is associated with significant morbidity and mortality. The present retrospective study was designed to evaluate the age-, gender-, and blood group-adjusted CMV seroprevalence among solid organ donors, representing fairly the overall Hungarian population (according to Hungarian Central Statistic Institute). This information is important for calculating risk-factors for CMV-seronegative recipients. No nationwide estimates of CMV seroprevalence in Hungary (as a representative of Eastern Middle Europe) have been published yet. METHODS: We investigated 2070 organ donors for CMV seroprevalence by measuring the CMV-specific immunoglobulin G. The donors were divided into 3 age groups (2-20, 21-50, and 51-70 years old). A study was also conducted on a fourth group consisting of 200 residents from an old age home. CMV seroprevalence differences were searched according to age-, gender- and blood-group distribution. RESULTS: The CMV seroprevalence of organ donors is 85% and of all investigated persons is 86%. The age-specific prevalence increases, starting from 72% in the first group to 99% in the fourth group. Seroprevalence of females was found to be significantly higher than of males (P=.0001). CONCLUSION: We have shown that the overall CMV seroprevalence in the Hungarian population is moderately high at 86%. The opportunity for CMV-seronegative recipients to get a graft from a seronegative donor is statistically only 2%. The seroprevalence of the youngest age group is 72% and so it can be concluded that the Hungarian population acquires the infection mainly in childhood or in the early adulthood. Female gender is a risk factor for CMV infection. This fact must be taken into consideration during the planning of patients' follow-up, prophylaxis, and therapy.

Renal cell carcinoma of the native kidney: a frequent tumor after kidney transplantation with favorable prognosis in case of early diagnosis.

INTRODUCTION: The frequency of malignant tumors as a cause of death is increasing among kidney transplant patients. The aim of our study was to characterize kidney tumors occurring in the native kidneys of renal transplanted patients, and to determine their impact on recipient survival. METHODS: We retrospectively analyzed the 43/3003 (1.43%) renal cell carcinomas (RCC) in the native kidneys of patients transplanted between 1973 and 2010. RESULTS: During this period we diagnosed 293 posttransplant tumors, 14.6% of which were RCC. The male/female ratio was 2.1:1. The mean age of recipients at the time of tumor detection was 52.4 ± 12.1 years. The mean time from transplantation to diagnosis was 72.4 ± 61.6 months. RCC occurred on both sides in similar numbers. Tumors were multifocal in 8 cases. According to TNM staging, RCC was stage I in 38 cases. The histologic type was clear cell (n=27), papillary (n=13), chromophobe (n=2) or sarcomatoid (n=1). Radical nephrectomy was performed in 41 cases. Immunosuppressive management was converted to proliferation signal inhibitors in 27 patients (sirolimus n=19 or everolimus n=8). Fifteeen patients died at a mean survival time of 38.9 ± 62.4 months with 28 patients still alive at a mean follow-up 43.8 ± 35.6 months. Cumulative survival according to the Kaplan-Meier method was 79.2% at 1 year, 66.1% at 5 years, and 59.0% at 10 years. The patient survival rate was better among papillary than clear cell RCC (P=.038). CONCLUSION: RCC was the second most frequent tumor among kidney transplanted patients at our center. The diagnosis established at an early stage in the majority of cases, leading to favorable patient survivals. A regular yearly abdominal ultrasound screening is suggested for early tumor diagnosis.

The impact of Milan criteria on liver transplantation for hepatocellular carcinoma: first 15 years' experience of the Hungarian Liver Transplant Program.

In addition to hepatitis C, hepatocellular carcinoma. is a leading indication for orthotopic liver transplantation (OLT). The indications for OLT in HCC remains a topic of debate. The successful Milan criteria are still accepted as the gold standard to select candidates with a good chance for long-term survival. The Hungarian Liver Transplant Program launched in 1995 reached 45 OLT/year in 2010. Among 412 first OLTs, there were 49 cases of a malignant tumor, including 41 among which the indication was the tumor. Of the 412 patients, 154 (37.4%) were hepatitic C virus (HCV) positive, including 29 with HCC and 23 cases in which HCC was the indication itself. Half of the HCC patients were within the Milan criteria; 50% exceeded the criteria. We observed a solitary HCC in 36% of cases: 2 foci in 18%; 3 in 7%, 4 in 14%, and ≥5 in 25%. Only 12 patients underwent a "down-staging" treatment before OLT: 8 radiofrequency ablation (RFA) and 4 transarterial chemoembolization (TACE). Cumulative 1-, 3-, and 5-year patient survivals were 62%, 54%, and 43%, respectively in HCC/HCV-positive patients and they were 74%, 67%, and 61% among non-HCC HCV-positive subjects. The cumulative HCC patient survival rates of 64%, 64%, and 53% among Milan criteria were superior to those of 57%, 40%, and 27% among subjects exceeding the Milan criteria (P=.01). Pre-OLT "down-staging" treatment increased the 1-year patient survival from 64% to 70%; however, it did not affect the long-term results. Among items of the Milan criteria tumor size had less impact on outcomes then number of foci. The majority of cases who exceeded the Milan criteria had been transplanted before 2003. Our results suggested that the Milan criteria should be applied for the selection of candidates in order to promise good survival after OLT for HCC.

Liver transplantation for acute liver failure: the Hungarian experience.

Acute liver failure (ALF) counts for 9%-11% of activity in leading liver transplant programs. We have summarized the Hungarian Liver Transplant Program experience for ALF among 412 consecutive orthotopic liver transplantations (OLTs). All OLTs were performed without an extended international donor background. The proportion of ALF among the indications for OLT was lower (5.8% vs 9%) and early mortality higher than the European Liver Transplant Registry (1 year cumulative patients survival is 70% in ELTR vs 60% in the HU LT Program). The waiting time for a donor was longer than expected in the Eurotransplant community. Regarding postoperative complications, there was a higher incidence of initial poor function, bacterial infection, sepsis, and multiorgan failure. We conclude that ALF can be managed with reasonable results but requires an extended donor pool with an integrated international network to improve postoperative morbidity and mortality.

Local drug delivery for percutaneous coronary intervention.

Since the first successful coronary angioplasty by Andreas Grüntzig in 1977, the field of percutaneous coronary intervention (PCI) has expanded rapidly. Rapid technological refinement has seen equipment and complementary pharmacotherapy to improve the outcome of PCI evolve dramatically, driven by clinical need and enormous market forces. The ideal intervention should expand the vessel lumen without inflicting endothelial injury, and provide local drug delivery to prevent subsequent acute thrombosis and neointimal hyperplasia. Drug eluting stents, once regarded as the "gold standard" in PCI, and established as the treatment of choice for nearly a decade, remain limited in their performance by important risks of in-stent restenosis and late stent thrombosis. In this review, we discuss need for local drug therapy as an adjunct to angioplasty and present exciting new technological advances to deliver local pharmacotherapy to the coronary artery, which will hopefully overcome some of the limitations of DES and may represent the way forward in coronary intervention.

Small difference in international normalized ratio may yield a significant impact on prioritizing patients listed for liver transplantation.

Priority for liver transplantation is currently based on the Model for End-stage Liver Disease (MELD) score. The aim of our study was to assess in detail the contribution of international normalized ratio (INR) differences for MELD scores because of interlaboratory variability. The samples from 92 cirrhotic patients were measured on different systems combining three coagulometers and three thromboplastin products to determine variations in INR and MELD score. The INR differences among the first four systems varied between 0 and 0.2, resulting in MELD differences of 0 to 2. The MELD scores of 92 patients changed only among 10 possible integers so that normally 2 to 10 patients shared the same MELD value. In some cases, one MELD score difference resulted in a 10 superpositioning on the waiting list. Including one more system (mechanical vs optical) into our investigations achieved a five MELD difference. Supposing an extreme situation where one patient competes with his or her lowest, all the other with their highest possible score (and visa versa), the difference may be even 20 positions, overturning the complete waiting list. In conclusion substantial interlaboratory differences in MELD score have profound clinical consequences.