Double rarity: malignant masquerade biliary stricture in a situs inversus totalis patient.

BACKGROUND: Situs inversus totalis is a rare anatomical variation of both the thoracic and the abdominal organs. Common bile duct strictures can be caused by malignant and benign diseases as well. 7-18% of the latter ones are 'malignant masquerade' cases, as pre-operative differentiation is difficult. CASE PRESENTATION: We present the case of a 68y male patient with known situs inversus totalis and a recent onset of obstructive jaundice caused by a malignant behaving common bile duct stricture. Technically difficult endoscopic retrograde cholangiopancreatography, brush cytology, magnetic resonance cholangiopancreatography, endoscopic ultrasound, and percutaneous transhepatic drainage with stent implantation were performed for proper diagnosis. Cholecystectomy, common bile duct resection with hilar lymphadenectomy, and hepatico-jejunostomy have been performed following multidisciplinary consultation. The final histology report did not confirm any clear malignancy, the patient is doing well. CONCLUSION: In situs inversus patients, both diagnostic and therapeutic procedures can lead to various difficulties. Benign biliary strictures are frequently misdiagnosed preoperatively as cholangiocellular carcinoma. Surgery is usually unavoidable, involving a significant risk of complications. The co-existence of these two difficult diagnostic and therapeutic features made our case challenging.

How Much Is the Inevitable Loss of Different Coagulation Factors During Blood Product-Free Liver Transplantations?

BACKGROUND: Bloodless liver transplantations (LT) have already been reported, but special characteristics of hemostatic changes remain less defined. The aim of this study was to evaluate the "inevitable" loss of coagulation factors (CF) in blood product-free LT. METHODS: Blood product and CF concentrate-free LT patient data were analyzed in terms of the first 2 days of perioperative hemostasis kinetics (N = 59). CF levels (FI, II, V, VII, X, and XIII), platelet (PLT) levels, and hemoglobin levels were measured before LT (T1), on arrival at the intensive care unit (T2), and 12, 24, and 48 hours after LT (T3, T4, and T5, respectively). Thromboelastographic (TEG) parameters were determined before and at the end of LT (T1-T2). RESULTS: Fibrinogen levels decreased by 1.2 ± 0.6 g/L, prothrombin levels by 26% ± 14%, factor V levels by 40% ± 23%, VII levels by 29% ± 19%, and X levels by 39% ± 22% (P < .001). From T2 to T4 fibrinogen increased by 0.9 ± 0.6g/L for 24 hours (P < .001). Factor II, V, and VII levels increased by 20% ± 16%, 31% ± 32%, and 12% ± 27%, respectively, between T3 and T5 (P < .001). However, factor X reached only half of the T1 level (T3-T5, P < .001). Platelet count increased in 34 (58%) patients at T2 (P < .001). The TEG parameters remained in the normal range during LT (T1-T2). CONCLUSION: The major findings of this study advocate that "inevitable" levels of CF decrease during LT by an average of 1.2 g/L in terms of fibrinogen and 23% to 40% regarding factors II, V, VII, and X. The authors suggest that knowing the "magic numbers" and comparing them against baseline laboratory results might predict the possibility of blood product-free transplant, providing confidence and safety to the surgeon and the anesthetist.

Mapping nursing interventions using the Therapeutic Intervention Scoring System in bloodless liver transplantations.

BACKGROUND: The Simplified Therapeutic Intervention Scoring System adapted to liver transplantation by King's College Hospital rank 138 activities to determine the nursing workload, diagnostic, monitoring and therapeutic needs. OBJECTIVES: To evaluate nursing activities of "King's-TISS" score grouped in organ systems and nurse patient ratio in the perioperative 48 hours of blood product free liver transplantations (LT). METHODS: The "King's-TISS" score's were analysed by nursing procedures and grouped, scored according to organ systems. The nursing workloads were studied during LT (T1), on arrival on the ICU (T2) and 12-24-48 hours after LT (T3-T4-T5). RESULTS: The total of "King's-TISS" score points were decreased by ≥20% daily (p = 0.001). The mean score of 104 ± 3.5 points (CI:104-105) during LT decreased to 84.7 ± 12 points (CI:83-86) in 48 hours (T5). The "metabolic" and "haemostasis" points increased (p = ).01), the "immunology" points unchanged (T2-T5) postoperatively. A slight decrease was observed in case of "basic nursing care", "monitoring", "neurologic support", "renal support" and "cardiovascular support" points (T2-T5, p < .01). The "invasive intervention" and "ventilatory support" points strongly decreased (T2-T5, p < .001). One "King's-TISS" point was found to equal 7.4 minutes with a nurse patient ratio of 2:1 intraoperatively and 1:1 postoperatively. CONCLUSION: Absence of blood product administration in LT decreases the total and organ specific workload, except the metabolic, haemostasis, immunology and basic support requirement. It was not within the scope of the King's-TISS score to analyse the application of viscoelastic haemostasis test and coagulation factor concentrate administration.

Multidrug resistance protein 2-mediated estradiol-17beta-D-glucuronide transport potentiation: in vitro-in vivo correlation and species specificity.

Multidrug resistance protein 2 (MRP2) is a multispecific organic anion transporter expressed at important pharmacological barriers, including the canalicular membrane of hepatocytes. At this location it is involved in the elimination of both endogenous and exogenous waste products, mostly as conjugates, to the bile. Estradiol-17beta-d-glucuronide (E(2)17betaG), a widely studied endogenous substrate of MRP2, was shown earlier to recognize two binding sites of the transporter in vesicular transport assays. MRP2 modulators (substrates and nonsubstrates) potentiate the transport of E(2)17betaG by MRP2. We correlated data obtained from studies of different complexities and investigated the species-specific differences between rat and human MRP2-mediated transport. We used vesicular transport assays, sandwich-cultured primary hepatocytes, and in vivo biliary efflux in rats. Our results demonstrate that the rat Mrp2 transporter, unlike the human MRP2, transports E(2)17betaG according to Michaelis-Menten type kinetics. Nevertheless, in the presence of modulator drugs E(2)17betaG transport mediated by the rat transporter also shows cooperative kinetics as potentiation of E(2)17betaG transport was observed in the vesicular transport assay. We also demonstrated that the potentiation exists both in rat and in human hepatocytes and in vivo in rats.

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.

Epidural anesthesia? No of course.

Although the contraindications for thoracic epidural anesthesia (TEA) are well defined, the debate continues about whether TEA improves outcomes. Pro and con trials and a metaanalysis in the past have yielded equivocal results; they did not deal with new vascular intervention or drugs. The benefit of TEA in surgery is to provide analgesia. In subgroups, TEA can decrease the mortality and morbidity. In contrast, the cost can increase in the situation of a complication that is opposite to the side effects is rare, but the impairment caused by them is out of proportion to the benefits. Primary or secondary prophylaxis with antithrombotic drugs is increasing in developed countries because of the increasing cardiovascular interventions and aging of the population. The neuroaxial guidelines are useful, but the changing of the coagulation profile after hepatectomy is not included in them. The decision to use TEA in liver surgery must be individualized with steps planned from the beginning. TEA suitability is based on an evaluation of the contraindications, comorbidities, coagulation profiles, hepatic reserve, and balance of benefits and risks. The insertion or withdrawal of the epidural catheter should be made with care according to the neuroaxial guidelines and in the presence of a normal TEG. The decreasing level of prothrombin content and platelet counts after hepatectomy should be closely monitored every 2 to 5 days.

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.

Factors in association with sepsis after liver transplantation: the Hungarian experience.

Sepsis is the major cause of patient death after orthotopic liver transplantation (OLT). To identify risk factors for sepsis, we analyzed all 199 primary OLTs performed between 1995 and 2004. Patients were divided into 2 groups according to whether they experienced sepsis after liver transplantation. Recipient, perioperative factors, and complications were subjected to univariate analyses. Statistically significant factors were exposed to multivariate analyses: Cox regression and Hosmer-Lemeshow test. Sepsis occurred in 45 (23%) patients. Recipient Child-Pugh score, preoperative broad spectrum antibiotic (meropenem) prophylaxis, intraoperative red blood cell transfusion, starch infusion, postoperative bleeding, hepatic artery thrombosis, and biliary leakage/necrosis were independent risk factors for sepsis. Our results agree with the international experience. A high amount of starch infusion and an extended use of broad spectrum antibiotics for prophylaxis adverse experiences in our center and have been removed from the protocol.

Mutation scanning of the p53 tumor suppressor gene in renal and liver transplant patients in Hungary.

INTRODUCTION: The increased incidence of malignancies among transplanted patients is well known. Abnormal function of the p53 tumor suppressor gene has been reported in more than half of all tumors. The aim of our study was to detect point mutations of p53 gene in transplanted patients because the presence of mutations may be a predictive factor for tumor development. An earlier diagnosis can help to develop new strategies for immunosuppressive therapies. METHODS: Three point mutations were chosen based on the literature: exon5-codon175, exon7-codon248, exon8-codon273. Genomic DNA from the plasma of 60 liver, 362 renal transplants, and 45 nontransplanted patients with different tumors and 20 suspected healthy patients were analyzed with a real-time PCR method using the Roche LightCycler. The mutations were evaluated by melting curve analysis. RESULTS: We elaborated a special protocol for scanning the above mentioned p53 point mutations, which were proved by sequencing as well. Among 487 patients, 486 showed a wild-type genotype. The only patient carrying a mutation at codon 273 (heterozygous) was a liver transplant patient, who developed pancreas carcinoma and had already died. CONCLUSION: Our data suggest that mutations of the targeted codons in leukocyte DNA seem to be rare, but a mutation could be lethal. The evaluated three point mutations of p53 gene were not predictive for tumor development.

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.

Experimental vascular graft for liver transplantation.

Hepatic artery thrombosis is a major cause of graft failure in liver transplantation. Use of donor interponates are common, but results are controversial because of necrosis or thrombosis after rejection. Reperfusion injury, hypoxia and free radical production determinate the survival. The aim of the study was to create an 'ideal' arterial interponate. Autologous, tubular graft lined with mesothelial cells, prepared from the posterior rectus fascia sheath, was used for iliac artery replacement in eight mongrel dogs for six months under immunosuppression. Patency rate was followed by Doppler ultrasound. Eight grafts remained patent and another two are patent after one year. The patency rate was good (median Doppler flow: 370 cm/sec) and there was no necrosis, thrombosis or aneurysmatic formation. The grafts showed viable morphology with neoangiogenesis, appearance of elastin, smooth muscle and endothelial cells. Electron microscopy showed intact mitochondrial structures without signs of hypoxia. Tissue oxygenation was good in all cases with normal (< 30 ng/ml) myeloperoxidase production. In conclusion, this autologous graft presents good long-term patency rate. Viability, arterialisation and low thrombogenicity are prognostic factors indicating usability of the graft in the clinical practice without the risk of rejection. Further investigations such as cell cultures and standardisation are necessary.

Experimental autologous substitute vascular graft for transplantation surgery.

Vascular complications in liver transplantation are a major cause of graft failure and mortality. The aim of the study was to create autologous vascular graft without risk of rejection. Posterior rectus fascia sheath lined with peritoneum was used for iliac artery replacement in seven mongrel dogs. The patency was followed by palpation and Doppler ultrasound. The grafts were removed after one month. Five grafts remained patent. The Doppler showed good, relatively increased flow (median flow rate: 383 cm/sec) after one month in all of the cases. Slight increase in diameter was present in all cases. By microscopy the five patent grafts showed viable morphology, fibroblasts, smooth muscle cells and thin fibrin layer in the wall. The grafts were lined partially with a neoendothelial monolayer and a thin fibrin layer. In conclusion, this graft presents an acceptable patency rate and low thrombogenicity, and could be useful in transplantation. Further investigations are needed to study the effect of immunosuppression and rejection on long-term morphology and patency of the grafts.

[Pathologic evaluation of orthotopic liver transplantation in Hungary]. / A hazai májtranszplantációk értékelése patológiai szempontból.

A total of 81 orthotopic liver transplantations were performed on 74 patients between January 1995 and December 1999 at the Department of Transplantation and Surgery of the Semmelweis University in Budapest. Indication for transplantation was liver cirrhosis in 57 cases, 10 patients were transplanted due to fulminant liver failure, while 7 patients underwent transplantation because of liver metastasis of different semimalignant tumours. During the above period, retrospective studies on 205 pre- and posttransplantation liver biopsies, 74 explanted livers, 7 explanted liver grafts and 22 autopsy cases were performed at the First Institute of Pathology and Experimental Cancer Research of the Semmelweis University in Budapest. A number of 116 protocol biopsies (dates as zero time, 7th day, 6th month and 12th month) and 73 non-protocol biopsies (taken due to liver allograft dysfunction) were analysed. Different gradings of acute rejection--characterised by trias of portal inflammation, venous endothelitis and bile duct damage--were detected in 62 cases. Chronic rejection occurred in 7 patients, with 4 cases of vanishing bile duct syndrome and one of the case of foam cell arteriopathy, add to 2 cases of chronic rejection characterized by undetermined bile duct damage. The present study includes the evaluation of 22 autopsy cases according to liver transplantation in Hungary, with the finding that liver allograft insufficiency was the main cause of mortality. Authors conclude that pathomorphological analysis has an important role in relation to liver transplantation.

[Qualitative and quantitative detection of hepatitis C virus RNA by PCR technique. Monitoring of viral copies after liver transplantation]. / Hepatitis C-vírus (HCV)-RNS kvalitatív és kvantitatív kimutatása PCR technikával. A HCV-RNS-kópiaszám monitorozása májtranszplantációt követóen.

The authors demonstrate the HCV nucleic acid amplification method is not wide-spread in Hungary yet. The HCV-RNA is usually detectable 2-4 weeks after infection independently the immunostate of the patients. The authors help to select the adequate measurement(s) in logical order when HCV infection is suspected. The benefit of the PCR method is emphasized. Monitoring of the HCV-RNA titer of the liver transplanted patients promotes to establish the fluctuation of HCV-RNA copies and the effectivity of therapy following transplantation. The detection of HCV-RNA by PCR method is a proof of an acute or chronic infection and rules out past infection. The quantitative PCR measurement is useful for determination of indication and control of efficacy of antiviral therapy.

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.

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.