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Background In the Eurotransplant, 12.6% of kidney transplantations are a repeat procedure. Third transplants are significantly more complex than first and second ones. We compared the results of first (PRT) versus third (TRT) transplantations. Methods Between 2011 and 2016, we performed 779 deceased donor adult kidney transplantations, 14.2% out of them were second, 2.6% (20) third, and 0.3% fourth. We compared the pre-, intra-, and postoperative data, kidney function, and survival rate. Results Recipients of TRT were younger (53.4 vs. 47.3 p = 0.02). HCV infection rate (20%, p = 0.00) is ten times higher. The operation time is longer (132 vs. 152 min, p = 0.02), and delayed graft function is much more frequent (22.4% vs. 60%, p = 0.00). Induction therapy was given to every TRT (7.9% vs.100%), but as a result, the rejection rate was the same (~ 15%). Hospital stay is a week longer. Patient’s survival at 1, 3, and 5 years for PRT is 96.4%, 93.9%, and 91.2% and for TRT is 90%, 85%, and 78.4%, respectively (p = 0.023). TRT’s odds ratio of fatal outcome is 4.35 (1.5–12.5). Graft survival at 1, 3, and 5 years for PRT is 93.1%, 91.4%, and 90.3% and for TRT is 75%, 75%, and 75%, respectively (p = 0.020). TRT’s odds ratio of graft loss is 3.14 (1.1–8.9). Of PRT 85.76%, out of PRT 85.76%, while out of TRT 60% live with a functioning graft, p=0.00149. Conclusion In a third transplant, both graft and patient survival are significantly inferior to primer ones. Careful selection is required to minimize the patient risk and graft loss.

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.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).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).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.

Donor's CYP3A-status (CYP3A5 genotype and CYP3A4 expression) can provide prognostic information regarding tacrolimus-metabolizing capacity of the liver graft and initial tacrolimus dosing for therapeutic blood concentrations in liver transplants. The present work prospectively investigated whether CYP3A-status guided tacrolimus therapy has any potential clinical benefit for recipients in the early postoperative period.The contribution of preliminary assaying of donor CYP3A-status to the optimization of initial tacrolimus therapy and to the reduction of adverse events (acute rejection, infection, nephrotoxicity) was investigated in 112 liver transplant recipients (CYPtest group) comparing to 101 control patients on tacrolimus concentration guided therapy.The time for achieving therapeutic tacrolimus concentration was significantly reduced, confirming potential benefit of initial tacrolimus therapy adjusted to donor's CYP3A-status over classical clinical practice of tacrolimus concentration guided treatment (4 vs 8 days, P0.0001). Acute rejection episodes (3.6 vs 23.8%, P0.0001) and tacrolimus induced nephrotoxicity (8 vs 27%, P = 0.0004) were less frequent in CYPtest group than in control patients, whereas occurrence of infectious disease was not influenced by tacrolimus dosing strategy (3.6 vs 5.9% in CYPtest and control groups, P0.05). Acute rejection was often accompanied with tacrolimus blood concentrations lower than 10 ng mLCYP3A-status guided therapy significantly improved the risk of misdosing induced early adverse effects (acute rejection, nephrotoxicity).

Absztrakt: Az új koronavírus okozta COVID–19-járvány kihívást jelent a szervátültetett betegek ellátását illetően is, ezért lényegesnek tartjuk az ezzel kapcsolatos friss ismeretek megosztását a hazai ellátásban dolgozók számára. Nagyobb esetszámmal májátültetettekről még nincsenek adatok az irodalomban, vesetranszplantáltak esetén azonban a spanyol és a francia adatbázisok 18,6%-os és 13%-os halálozásról számoltak be, ami kissé magasabb az ottani átlagpopulációénál. Tünetmentes esetekben SARS-CoV-2-pozitív PCR-eredmény birtokában nem szükséges a transzplantáltak immunszuppresszív terápiáján változtatni, azonban láz, gastrointestinalis vagy légúti tünetek kialakulását követően a mikofenolsav és mTOR-gátló készítmények elhagyása javasolt, és a kalcineurininhibitorok vérszintjét a legalacsonyabb effektív szintre kell csökkenteni. Tüdőkárosodás észlelését követően vesetranszplantáltak esetében a kalcineurininhibitorokat is le kell állítani, míg a májtranszplantáltak esetében a dózis csökkentése szükséges a fenntartó kortikoszteroid mellett. Ez utóbbi dózisának emelése szükséges hyperinflammatiós szindróma (HIS) kialakulásakor. A HIS terápiás befolyásolására transzplantáltakban is sikerrel lehet alkalmazni az IL1- és IL6-gátló monoklonális antitesteket. Célzott vírusellenes készítmény nem áll rendelkezésre, a legszerencsésebb, ha a beteg bevonható a remdesivir vagy a favipiravir klinikai vizsgálatába. A hidroxiklorokin transzplantáltaknak is adható, bár hatékonysága és biztonságossága kérdésessé vált. A lopinavir/ritonavir kombináció a kalcineurininhibitorokkal fennálló súlyos gyógyszerkölcsönhatás miatt nem adható. A SARS-CoV-2 cytopathiás hatása endotheldiszfunkciót okoz, amely prokoaguláns állapot kialakulásához vezet, emellett megváltozik a renin-angiotenzin-aldoszteron rendszer egyensúlya is. Fontos ezért a betegek kezelése során a thrombosisprofilaxis korai elkezdése alacsony molekulasúlyú heparinnal és alacsony dózisú acetilszalicilsavval. Az angiotenzinkonvertálóenzim-gátló (ACEI) és az angiotenzin-II-receptor-antagonista (ARB) terápiára beállított betegek kezelését a COVID–19 miatt nem szabad abbahagyni. Orv Hetil. 2020; 161(32): 1310–1321.

Absztrakt: Bevezetés: Nemzetközi tapasztalatok alapján a COVID–19-fertőzött, kórházban kezelt betegek több mint 30%-ában vénás, artériás és microvascularis thrombosis, disszeminált intravascularis véralvadási zavar, illetve thromboembolia alakul ki. Ennek laboratóriumi jellemzői a magas D-dimer- és fibrinogénszint, valamint a megnyúlt prothrombinidő és aktivált parciális thromboplastinidő. Módszer: Az esetbemutatások során intenzív osztályon kezelt, COVID–19-fertőzött betegek (n = 3) ClotPro® trombolasztométeres (EX-test, IN-test, FIB-test, RVV-test és TPA-test) eredményeit értékeltük a klinikai állapottal összefüggésben. Eredmények: A ClotPro®-paraméterek procoagulatiót, hypercoagulatiót, fibrinolysist vagy annak „shut down” megnyilvánulását jelezték, és összhangban voltak a hagyományos alvadási tesztekkel, illetve a kompenzált disszeminált intravascularis coagulopathia meghatározásával. Következtetés: Eredményeink magyarázatot adhatnak a vénás thromboemboliás szövődményekre, támogatják a terápiás alvadásgátló kezelés és a thrombocytaaggregáció-gátlás fontosságát. A gyógyszer típusának, adagolási algoritmusának, optimális időtartamának meghatározásához intervenciós klinikai vizsgálatok szükségesek, ezek engedélyeztetése folyamatban van. Orv Hetil. 2020; 161(22): 899–907.

We aimed to emphasize the prognostic impact of differences included in the 8th versus the previous 7th edition of AJCC (American Joint Committee on Cancer) Cancer Staging manual for hepatocellular carcinoma (HCC). A number of 87 consecutive HCCs were retrospectively evaluated and staged, using the 7th and 8th edition of AJCC staging systems. The clinicopathological parameters were correlated with the overall survival rate. No preoperative chemotherapy was received by any of the patients. According to the 7th edition of AJCC manual, 52 of the 87 cases were staged as pT2 and 35 as pT1. After restaging, according to the 8th edition, 23 of the 52 pT2 cases were understaged as pT1b, and the rest of the 29 remained as pT2. Regarding the 35 HCCs classified as pT1, using 7th edition, all of them were restaged as pT1a. Compared to the 7th staging system, using the 8th edition of AJCC manual, the percentage of pT2 tumors significantly decreased, from 59.77 to 33.33%. The patient’s gender, age, tumor focality, and grade of differentiation did not prove to have any prognostic value. Regarding pT stage, it does not influence the overall survival rate, independently from the used staging system. The staging criteria, in the most recent edition of AJCC, are simplified and allowed tumor understaging. These changes do not have independent prognostic value. The prognostic impact of pT understaging should be evaluated in larger cohorts.

Absztrakt: Bevezetés: A májtranszplantáció során a haemostasis a hagyományos alvadásifaktor-szintekkel és a viszkoelasztikus tesztekkel monitorizálható, nem szokványos megközelítése a coagulatiósfaktor-specifikus vérveszteség dinamikus követése. Célkitűzés: Kutatásunk célja az alvadásifaktor-specifikus vérveszteség alapján kiszámolt térfogati tartalékok vizsgálata, a vér- és faktorkészítmény-mentes májtranszplantáció első 48 órájában a Child–Pugh-score tükrében is. Módszer: 59, vér- és faktorkészítményt nem igénylő, májtranszplantált beteg hagyományos alvadásifaktor-szintjeit, viszkoelasztikus paramétereit és faktorspecifikus vérveszteségeit elemeztük Gross-metódus segítségével, kiindulási és „coagulopathiás” triggerszintek alapján. A haemostasistartalékokat Child–Pugh-osztályozás szerint is összehasonlítottuk. A hagyományos laboratóriumi vizsgálatok és a faktorspecifikus térfogati tartalékok kiszámítása a májtranszplantáció előtt (T1), végén (T2) és 12–24–48 órával utána (T3–T4–T5) történt. A viszkoelasztikus tesztek eredményeit a májtranszplantáció előtt (T1) és végén (T2) rögzítettük. Eredmények: A műtét végére az alapszintről a fibrinogén 1,2 g/l-rel, míg a protrombin és az V-ös, a VII-es és a X-es faktor 26–40%-kal csökkent. A posztoperatív időszakban a fibrinogénszint 0,9 g/l-rel (T2–T4, pKövetkeztetés: A haemostasis térfogatalapú megközelítése kiegészíti a hagyományos laboratóriumi vizsgálatokat és a viszkoelasztikus teszteket, mivel dinamikusan jelzi a haemostasis aktuális tartalékát faktoronként, és a „leggyengébb láncszemet” mutatja meg a rendszerben. Orv Hetil. 2020; 161(7): 252–262.

Absztrakt: Bevezetés: A Wilson-kór a rézanyagcsere ritka, kezelés nélkül fatális, öröklődő megbetegedése. Bár a diagnosztika és a kezelés jelentős fejlődésen ment át az elmúlt években, számos beteg esetében ma is májátültetésre van szükség. Célkitűzés: A vizsgálat célja a Magyarországon Wilson-kór miatt májátültetésen átesett betegek adatainak összegyűjtése és feldolgozása volt. Módszer: Retrospektív módon vizsgáltuk a Semmelweis Egyetemen 1996 és 2017 között Wilson-kór miatt májátültetésen átesett 24 beteg adatait. A Wilson-kór diagnózisa minden esetben a nemzetközi, lipcsei pontrendszeren alapult. A heveny májelégtelenség felállításához a King’s College-kritériumrendszert használtuk. A májátültetések a Semmelweis Egyetem Transzplantációs és Sebészeti Klinikáján történtek, első alkalommal 1996-ban. Eredmények: Az átlagéletkor 26 év volt, a nő/férfi arány 13/11. 12 beteg heveny májelégtelenség miatt, 12 beteg dekompenzált cirrhosis miatt esett át májátültetésen. Egy beteg krónikus rejekció miatt retranszplantációra került. Három heveny májelégtelen beteg az Eurotransplant segítségével kapott új májat. A várólistán eltöltött átlagos idő 3 nap volt a heveny májelégtelen betegek, míg 320 nap a dekompenzált májbetegek esetében. Az ötéves túlélés 66% volt, azonban a 2002 után transzplantáltak esetében 80%, ami a tanulási folyamatot és a májátültetés elérhetőségének javulását jelezheti. A diagnosztika nehézségei ellenére a betegek többségében (21/24 beteg) már a műtét előtt ismert volt a Wilson-kór. Következtetések: Bár a Wilson-kór diagnosztikája és kezelése jelentős fejlődésen ment át az elmúlt évek során, ma is számos esetben van szükség májátültetésre. A betegek megfelelő kiválasztása és a transzplantáció időzítése jelentősen javítja a betegek túlélését. Orv Hetil. 2019; 160(51): 2021–2025.

There is very limited experience regarding the interventional radiological treatment of adrenocortical cancer (ACC). We present the case of a 57-year-old female patient with a large, potentially unresectable left-sided ACC and two hepatic metastases. Both liver tumors were effectively treated by trans-arterial embolization (TAE), followed by TAE of the bulky primary tumor as a life-saving intervention necessitated by severe intratumoral bleeding. Surgical removal of the primary tumor revealed complete necrosis. The patient is considered tumor free after 3.5 years. To the best of our knowledge, this is the first report to show that even a primary ACC may be completely ablated by selective embolization, and the fourth to prove the curative potential of liver TAE for ACC metastases. This case highlights the potential of selective embolization in ACC treatment.

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.

Introduction Hungary joined Eurotransplant International (ET) to improve the chance of transplantation for Hungarian patients and patient outcomes, including access and graft and patient survival. After 5 years of full membership, the evaluation of numbers and quality indicators is possible. Method A comparison was made between 5 years prior to a preliminary cooperation agreement (2007-2011) and 5 years after full ET membership (2014-2018). During the 2 study periods, we analyzed numbers and circumstances of deceased organ donors, multiorgan donors, donated organs, and transplantations in Hungary and development of waiting lists along with international organ exchanges. Result The number of actual organ donors increased by 22.09% (729 vs 890), an additional 823 organ removals represents an increase of 42.71% (1927 vs 2750). There were 46.51% more transplants managed in the selected periods (1561 vs 2287). The number of new patients on the waiting list increased (2305 vs 3247; 40.87%). The mean kidney mismatch number decreased from 3.21 to 2.96. Conclusion Joining ET has been an effective and efficient in terms of increasing access to organs and the lives of patients on the Hungarian waiting list posttransplant. It is also a benefit for patients with special needs because the number of organ transplants is greater than the increased number of donors.

Background and Aims Pretransplant or de novo donor specific antibodies (DSA) may lead to active or chronic active antibody mediated rejection (a and cABMR) as leading cause of graft loss after kidney transplantation. There is no treatment protocol approved for ABMR. Anti Il-6 tocilizumab (TCZ), inhibitor of DSA production, is a potential approach to stabilize kidney allograft function, however, evidence based results are not available. In our retrospective case series analysis, we assessed the changes in DSA and eGFR during and at the end of treatment with TCZ. Method In our single center case series analysis, 10 kidney transplant patients with biopsy proven ABMR (aABMR 6, cABMR 4, age 43±10.5ys, 6 males, time since transplantation 18(2-119)months, 7 first transplant, serum creatinine 224±80 umol/L at baseline) were studied between January 2017 – June 2019. Total plasma exchange (PE) (5x) was followed by TCZ (8 mg/kg, 1x monthly for 6 months) in case of a and cABMR. Intravenous immunoglobulin (IVIG, 1gr/kg) was added in case of aABMR. Routine laboratory parameters and DSA were reported retrospectively. Results 6 aABMR patients completed the treatment protocol. Class I DSA decreased significantly (MFI 4457(635-14084) vs. 877(595-5678); p=0.007), but Class II DSA remained the same during the treatment (MFI 4725 (586-17615) vs. 8097 (671-14636) p=NS). eGFR of aABMR patients and 1 cABMR patient were stabilized. 3 cABMR patients returned to dialysis. Reversible elevation of liver transaminases were detected in three patients. There was no any serious adverse event recorded. Conclusion The opportunely timed TCZ seems to be effective in reducing Class I DSA and stabilize graft function in patients with aABMR. Further studies are needed to prove the long-term efficacy and the exact role of TCZ in cABMR among kidney transplant patients.

Purpose. To present a comprehensive review of the literature data, published between 2000 and 2019 on the PubMed and Web of Science databases, in the field of the tumor microenvironment in hepatocellular carcinoma (HCC). All the data were combined with the personal experiences of the authors. Design. From 1002 representative papers, we selected 86 representative publications which included data on epithelial-to-mesenchymal transition (EMT), angiogenesis, cancer stem-like cells (CSCs), and molecular background of chemoresistance or resistance to radiotherapy. Results. Although the central event concerns activation of the Wnt/β-catenin pathway, other signal pathways, such as c-Met/HGF/Snail, Notch-1/NF-κB, TGF-β/SMAD, and basic fibroblast growth factor-related signaling, play a role in the EMT of HCC cells. This pathway is targeted by specific miRNAs and long noncoding RNAs, as explored in this paper. A central player in the tumor microenvironment proved to be the CSCs which can be marked by CD133, CD44, CD90, EpCAM, and CD105. CSCs can induce resistance to cytotoxic therapy or, alternatively, can be synthesized, de novo, after chemo- or radiotherapy, especially after transarterial chemoembolization- or radiofrequency ablation-induced hypoxia. The circulating tumor cells proved to have epithelial, intermediate, or mesenchymal features; their properties have a critical prognostic role. Conclusion. The metastatic pathway of HCC seems to be related to the Wnt- or, rather, TGFβ1-mediated inflammation-angiogenesis-EMT-CSCs crosstalk link. Molecular therapy should target this molecular axis controlling the HCC microenvironment.

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.

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.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).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).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.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.

AIMS Inter-individual variability in dose requirements of calcineurin inhibitors (CNI) has been linked to genetic polymorphisms of CYP3A enzymes. CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles of liver grafts may explain about one third of the inter-individual differences in pharmacokinetics of ciclosporin and tacrolimus in recipients. However, non-genetic factors, influencing CYP3A expression, can contribute to the variability of CYP3A function due to phenoconversion. The present study evaluated the association between CYP3A4 expression combined with CYP3A5 genotype of donor livers and recipients' CNI therapy after transplantation. METHODS The contribution of donors' CYP3A5 genotype and CYP3A4 expression to the blood concentrations and dose requirements of CNIs was evaluated in 131 liver transplant recipients. RESULTS The recipients with grafts from normal CYP3A4 expresser donors carrying CYP3A5*3/*3 required CNI maintenance doses more or less similar to the bodyweight-controlled starting doses (9.1 mg kg(-1) of ciclosporin and 0.1 mg kg(-1) of tacrolimus). The patients transplanted with grafts from low CYP3A4 expressers required substantial reduction (by about 50%, 4.2 mg kg(-1) of ciclosporin, 0.047 mg kg(-1) of tacrolimus, P < 0.001), while the recipients with grafts from high expressers or with grafts carrying at least one copy of the functional CYP3A5*1 allele required an increase (by about 50% [12.8-13.8 mg kg(-1)] for ciclosporin and 100% [0.21 mg kg(-1) ] for tacrolimus, P < 0.001) of the initial CNI dose for achieving target blood concentrations. CONCLUSIONS Donor livers' CYP3A-status, taking both CYP3A5 allelic variations and CYP3A4 expression into account, can better identify the risk of CNI over- or underexposure, and may contribute to the avoidance of misdosing-induced graft injury in the early post-operative period.

Summary The purpose of our study was to investigate the anatomical variations of the extrahepatic arterial structures of the liver with particular attention to rare variations and their potential impact on liver surgery. A total of 50 human abdominal organ complexes were used to prepare corrosion casts. A multicomponent resin mixture was injected into the abdominal aorta. The portal vein was injected with a different colored resin in 16 cases. Digestion of soft tissues was achieved using cc. KOH solution at 60–65 °C. Extrahepatic arterial variations were classified according to Michels. All specimens underwent 3D volumetric CT reconstruction. Normal anatomy was seen in 42% of cases, and variants were seen in the other 58%. No Michels type VI or X variations were present; however, in 18% of cases the extrahepatic arterial anatomy did not fit into Michels' classification. We report four new extrahepatic arterial variations. In contrast to the available data, normal anatomy was found much less frequently, whereas the prevalence of unclassified arterial variations was higher. We detected four previously unknown variations. Our data may contribute to the reduction of complications during surgical and radiological interventions in the upper abdomen.

Multiple duct anastomoses during LLS transplantation increase the incidence of biliary complications. The optimal plane of hepatotomy that results in the least number of bile ducts at the surface was investigated according to LHD variations. Ducts of 30 human livers were injected with resin and LHD branching on 3D-CT reconstructions were analyzed. Ducts on the virtual hepatotomy surface were estimated in three splitting lines. Variations with subtypes were described. Ia (66.7%): ducts from segments (S.) II-III form a common trunk and S.IV duct joins it. Ib (10%): common trunk formed by ducts from S.II-S.III while S.IV duct joins the common hepatic duct. IIa (16.67%): S.IV duct drains into S.III duct. IIc (3.33%): S.IV duct drains into both S.II and S.III ducts. III (3.33%): trifurcation of S.II, S.III and S.IV ducts. When the virtual hepatotomy line was on the FL, there was a single duct for the anastomosis in 30% of cases but two, three, or four ducts in 53.3%, 10%, and 3.3%, respectively. Division 1 cm to the right of the FL resulted in one duct (70%), but S.IV duct injury may occur. LLS hepatotomy should not necessarily be performed along the FL. Variations must be taken into consideration to minimize the number of biliary anastomoses during liver implantation.

Although experimental autologous patch or tubular conduit vascular grafts made from the internal rectus fascia sheath (IRFS) have been reported in the literature, thorough morphological evaluation and verification of the histological arterialisation of such grafts are lacking. Four purpose-bred Beagle dogs were utilised to create eight arterial internal rectus fascia sheath (ARFS) grafts implanted between bisected ends of the external iliac arteries. Four out of the eight ARFS grafts were patent after three months. Haematoxylin-eosin and Azan staining verified that the grafts gained a vessel-like layered structure with the presence of large amounts of collagen fibres. Although the inner surface of the intact IRFS was originally covered with claudin-5-negative and pancytokeratin-positive mesothelial cells in control samples, the internal cells of the ARFS grafts became claudin-5 positive and pancytokeratin negative like in intact arteries. Spindle-shaped cells of the wall of ARFS grafts were α-smooth muscle actin (α-SMA) positive just like the smooth muscle cells of intact arteries, but α-SMA immunoreactivity was negative in the intact IRFS. According to these findings, the fibroblast cells of the ARFS graft have changed into myofibroblast cells. The study has proved that ARFS grafts may be used as an alternative in arterial replacement, since the graft becomes morphologically and functionally similar to the host vessel via arterialisation.

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.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.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.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.

Hepatocellurar carcinoma (HCC) is the most frequent primary hepatic tumor, the vast majority of patients have less than a 12 month survival rate. The aim of this study was to evaluate the efficacy of TACE in patients with HCC, based on a case series and literature review. The study included 12 consecutive patients with HCC who underwent surgical treatment (resection, liver transplantation � resection) at the Department of Transplantation and Surgery, Semmelweis University, Budapest, during 2009-2015. All the patients received at least one TACE session. Patients with BCLC B-stage who benefit from TACE and another alternative therapy (eg, RFA) may be associated with or exhibit tumor stagnation, or tumor necrosis in most cases. In C BCLC stages, desperate cases - the two patients to whom TACE was the last therapeutic attitude, despite the predicted prognosis, TACE assured the prolongation of life and increased life quality. In the majority of patients in this study, stage A BCLC, chemoembolization was a therapeutic attitude that allowed subsequent liver transplantation (when it was not feasible initially due to tumor size) or liver resection in apparently inoperable cases. The arterial chemotherapy is the unanimously accepted indication in patients with stage B, BCLC. The data presented encourages us to opt for TACE with the intention of destaging BCLC and giving an operability character to the hepatic tumors (resection � hepatic transplantation). In stage C BCLC, TACE can be a last attempt to improve the quality of life and to control tumor progression.

Management of hepatitis C virus recurrence is a challenge after liver transplantation.The aim of the authors was to analyse the outcome of liver transplantation performed in hepatitis C virus positive patients during the past ten years and to compare recent data with a previous report of the authors.The authors retrospectively evaluated the data (donors, recipients, perioperative characteristics, patient and graft survival, serum titer of hepatitis C virus RNA, histology) of 409 patients who underwent liver transplantation between 2003 and 2012.156 patients were transplanted due to hepatitis C virus associated liver cirrhosis (38%). Worse outcome was observed in these patients in comparison to hepatitis C virus negative recipients. The cumulative patient survival rates at 1, 5, and 10 year were 80%, 61%, 51% in the hepatitis C virus positive group and 92%, 85%, 79% in the hepatitis C virus negative group, respectively (p0.001). The cumulative graft survival rates at 1, 5 and 10 year were 79%, 59% and 50% in hepatitis C virus positive and 89%, 80% and 70% in hepatitis C virus negative patients (p0.001). Hepatitis C virus recurrence was observed in the majority of the patients (132 patients, 85%), mainly within the first year (83%). The authors observed recurrence within 6 months in 71 patients (56%), and within 3 months in 26 patients (20%). The mean hepatitis C virus recurrence free survival was 243 days. Higher rate of de novo diabetes was detected in case of early recurrence. The cumulative patient survival rates at 1, 3, 5, 10 years were 98%, 89.5%, 81% and 65% when hepatitis C virus recurrence exceeded 3 months and 64%, 53%, 30.5% and 30.5% in patients with early recurrence (p0.001).Poor outcome of liver transplantation in hepatitis C virus positive patients is still a challenge. Hepatitis C virus recurrence is observed earlier after liver transplantation in comparison with a previous report of the authors. De novo diabetes occurs more frequently in case of early recurrence. Despite an immediate start of antiviral treatment, early recurrence has a significant negative impact on the outcome of transplantation.Bevezetés: A hepatitis C-vírus-fertőzés kiújulása továbbra is kihívás májátültetést követően. Célkitűzés: Az elmúlt tíz évben hepatitis C-vírus-infekcióval transzplantált betegek adatainak elemzése, összevetése korábbi eredményeinkkel. Módszer: A szerzők vizsgálták a donor és recipiens perioperatív adatait, a túlélést, a szövődmények arányát a hepatitis C-vírus-infekcióval összefüggő és egyéb indikációval végzett májátültetések, valamint korai és késői hepatitis C-vírus-infekció kiújulása esetén. Eredmények: 409 beteg közül 156 hepatitis C-vírus-pozitív beteg került májátültetésre (38%). A hepatitis C-vírus-fertőzött betegek túlélése és a grafttúlélés is rosszabb volt, mint egyéb indikációval végzett májátültetések esetén. A betegek 85%-ában a kiújulás igazolható volt, többségüknél egy éven belül. Három hónapon belüli rekurrencia igazolódott 26 betegnél. A májátültetéstől a vírus kiújulásáig átlagosan 243 nap telt el. A betegtúlélés három hónapon belül észlelt kiújulás esetén szignifikánsan rosszabb volt, mint három hónapon túli kiújulás esetén. Következtetések: A szerzők korábbi közléséhez képest az utóbbi tíz évben a víruskiújulást hamarabb észlelték. Korai kiújulás a prognózist lényegesen rontja, a rövid időn belül megkezdett antivirális kezelés ellenére. Orv. Hetil., 2013, 154, 1058–1066.

There are only few malignant tumours where organ transplantation is the treatment of choice. Transplantation can be considered individually in certain lung carcinomas, unresectable heart tumours, cholangiocellular carcinoma and Klatskin tumour. It is acceptable in unresectable chemosensitive hepatoblastoma, epitheloid haemangioendothelioma, liver metastasis of neuroendocrine tumours and as the most common indication, the early hepatocellular carcinoma (HCC) in cirrhotic liver. Results of liver transplantation (LT) for HCC according to Milan criteria as a "gold standard" are excellent. Time of LT has a great influence on the results. While patients are on waiting list, locoregional therapies may help prevent tumour progress. Living donor LT is an acceptable treatment of HCC. The greatest experience with this procedure is in Asia. Despite the favourable results, LT as the treatment of HCC is debated and raises several questions: regarding indication and expectable outcome. Milan criteria seem to answer this questions although they are too strict. The number and size of HCC foci per se is not sufficient predictor of eligibility to transplantation and for prognosis. Majority of the prognostic factors can be evaluated only after transplantation with pathological examination of HCC. Aim of the present research is to find prognostic factors that are characteristic of biological behaviour of HCC, which can be detected before LT in order to select patients who have the greatest benefit from LT. Re-definition of eligibility criteria is an actual question; an international consensus based on additional prospective studies is required for the "new" recommendation.

The complications caused by the rarely viral infections are more frequently treated in ICU (intensive care unit). The world paid attention to the WNV (West Nile virus) infections only in 1999, when 62 meningoencephalitis were registered in New York State. Six cases of WNV occur annually in Hungary. The authors present the first transplanted Hungarian patient with WNV encephalitis. The patient was hospitalized with epigastric pain, diarrhea, continuous fever, and decreasing amount of urine. The first checkup of infectious diseases was without any result. Although using of empirical antimicrobal therapy, the multiorgan failure patient remained febrile. On the basis of clinical signs, meningitis or encephalitis was suspected despite negative results of repeated cultures. On the 8th day, WNV infection was confirmed by serological examinations. With intravenous immunoglobulin therapy used within confines of supportive treatment, the patient became afebrile. After 21 days in ICU with good graft function, the patient was moved to the ward and he left the hospital after two more weeks. Until now, no prophylactic or etiological treatment has been developed for WNV. The early treatment is done with immunoglobulin or interferon; otherwise therapy has only supportive function. The disease caused by virus is more aggressive in transplanted patients and could be caused death.

IntroductionHepatic artery complication represents recognized sequel of liver transplantation that carries significant morbidity and mortality. Besides retransplantation, hepatic artery recanalization is provided surgically, or by percutaneous angioplasty and stent placement. This study provides an analysis of a single center experience comparing surgical and interventional treatments in cases of early hepatic artery complications.MethodsIn this retrospective single center study, 25 of 365 liver transplant recipients were enrolled who developed early hepatic artery complication after transplantation. Percutaneous intervention was performed in 10 cases, while surgical therapy in 15 cases. Mean follow-up time was not different between the groups (505±377 vs. 706±940 days, respectively).Results6 patients in the Intervention Group and 10 patients in the Surgery Group are alive. The retransplantation rate (1 and 3) was lower after interventional procedures, while the development of biliary complications was higher. The mortality rate was higher after operative treatment (2 and 5).ConclusionInterventional therapy is a feasible and safe technique for treatment of early hepatic artery complication after transplantation. Being less invasive it is an invaluable alternative treatment having results comparable to surgical methods.

Background Availability of suitable donor organs has always limited the number of liver transplantations performed. Use of marginal donor organs is an alternative to overcome organ shortage. Objective To analyze the effect of various combinations of donor organ quality and recipient status on the outcome of liver transplantation. Materials and Methods Data from 260 whole-liver transplantations performed between January 2003 and September 2009 were analyzed retrospectively. Study groups were established according to donor organ quality (marginal score 0–1 vs 2–5) and recipient status (Model for End-Stage Liver Disease [MELD] score 17). In patients at low risk, 102 received optimal grafts (good-to-good group [G/G], and 75 received marginal grafts (bad-to-good group [B/G]. In patients at high risk, 46 received optimal grafts (good-to-bad group [G/B], and 37 received marginal grafts (bad-to-bad group [B/B]. Results No differences were observed in cumulative patient and graft survival rates; however, total survival differed in the early period after transplantation, that is, within 1 year. There was a higher rate of overall postoperative complications including initial poor graft function, bleeding, infection, and kidney failure in group B/B compared with group G/B (25 of 37 patients [67.5%] vs 27 of 46 patients [59.0%]), group B/G (25 of 37 patients [68%] vs 39 of 75 patients [52%], and group G/G (25 of 37 patients [68%] vs 43 of 102 patients [42%]) ( P = .04). Patients with a high MELD score (G/B and B/B) demonstrated increased risk of postoperative complications. Use of donor organs with marginal score of 2 or higher in patients with high MELD scores increased early patient mortality. Conclusion In summary, patients with a high MELD score (G/B and B/B) are at an increased risk of post-OLT complications. In contrast, use of marginal grafts (B/G and B/B) increased the rate of hepatitis C virus recurrence and decreased the response rate to antiviral therapy. The combination of impaired donor grafts and recipients at high risk should be avoided.

Background Combined liver-kidney transplantation (CLKT) is a widely used multiorgan transplantation with good graft survival rates. Previous studies have shown beneficial effects of renal replacement therapy in critically ill patients. This observation led us to use intraoperative continuous veno-venous hemofiltration (CVVH) during multiorgan transplantations. Methods We analyzed (CRP) inflammatory response parameters of tumor necrosis factor (TNF)α, interleukin(IL)-6, procalcitonin (PCT) and C-reactive protein (CRP) at various stages of the combined transplantations. Results All patients survived with well-functioning grafts. Mean ± SD follow-up was 32.8 ± 14.2 months. During the whole operation we used intraoperative CVVH starting at the beginning and continuing in the intensive care unit (ICU) afterward (mean ± SD, 11.2 ± 8.4 hours). Intraoperative TNFα, IL-6, CRP, and PCT were measured before surgery, during hepatectomy in the anhepatic phase, before and after liver reperfusion, exactly before kidney reperfusion, after kidney reperfusion, and upon arrival in the ICU. The wash-out of cytokines together with hemodynamic stability gave optimal circumstances for recovery of the transplanted organs. Conclusions CVVH-based therapy offered stable intraoperative parameters, prevention of fluid overload, correction of metabolic disturbances, and wash-out of cytokines, which gave optimal circumstances for recovery of transplanted organs.

A de novo diabetes mellitus a májátültetés gyakori szövődménye.Célkitűzés:A de novo diabetes gyakoriságát, jelentőségét és a kockázati tényezők szerepét vizsgáltuk.Módszer:1995 és 2009 között 310 májátültetett beteg adatait dolgoztuk fel retrospektív módszerrel. De novo diabetest állapítottunk meg, ha az éhomi vércukor a 3. posztoperatív hónapon túl ismételten >6,8 mmol/l volt, és/vagy a májátültetés után tartós, a 3. posztoperatív hónapot meghaladóan is fenntartott antidiabetikus terápia indult.Eredmények:De novo diabetes a betegek 20%-ánál (63 beteg) alakult ki. A de novo és a kontrollcsoport között az alábbiakban találtunk különbséget. Donor-testtömegindex (24±3 vs. 22,4±3,6 kg/m2, p = 0,003), férfi nem (58% vs. 33%, p = 0,002). Recipienséletkor (47,6±7,2 vs. 38,3±14,6 év, p2, pKövetkeztetés:Májátültetést követő de novo diabetes kockázati tényezői az időskor, elhízás, férfi nem és a C-vírus okozta cirrhosis. Víruspozitív betegek körében a korai rekurrencia, súlyosabb viraemia és az antivirális kezelés ellenére kialakuló súlyosabb fibrosis összefügg a de novo diabetes kialakulásával.

The value of urinary cytology in the diagnosis of different pathological conditions in renal transplantation is particularly important. Manual microscopic urinalysis is a high-volume procedure that currently requires significant labour. Objective: To automate the sediment evaluation and to make this more accurate using the Iris Diagnostics Automated Urine Microscopy Analyzer (iQ200). Our goal was to compare the manual and automated microscopic data to apply iQ200 in renal function monitoring. Method: The iQ200 uses digital imaging and Auto Analyte Recognition software to classify urine constituents into 12 analyte categories and quantitatively report. Results: We determined cut-off values of urine particles in every category, which correlated well with manual microscopic results. The iQ200 was more sensitive for pathological casts than manual microscopic analysis. iQ200 helped the operator to differentiate between isomorphic and dismorphic erythrocytes and between lymphocytes and granulocytes, too. Every pathological constituent could be recognized, which is very important for early recognition of renal impairment, graft rejection and urinary tract infection. Conclusions: The iQ200 system automatically classifies 12 particles, significantly reducing the need for additional sample preparation, manual microscopic review achieving a high degree of standardization in urinalysis.

A májátültetés rutinszerűen, jó eredménnyel alkalmazott eljárás a végstádiumú májelégtelenség kezelésében. A transzplantáció után kialakuló éreredetű szövődmények közül a legritkább a májkapuér-szűkület. Ennek intervenciós radiológiai megoldását mutatjuk be három eset kapcsán. Célkitűzés: A portalis véna szűkületének sebészi kezelése kockázatos, különösen a korai poszttranszplantációs időszakban. Az intervenciós radiológiai beavatkozások általában kis megterheléssel, kevés szövődménnyel alkalmazhatók. Célunk bemutatni a percutan transhepaticus fémstentbehelyezés biztonságosságát, eredményességét. Módszer: Háromszázkilencvenhat májátültetés után összesen három esetben (0,07%) észleltük az anasztomózis korai beszűkülését. Ezekben az esetekben ultrahangvezérelt percutan transhepaticus venaportae-punkciót végeztünk vékony tűvel, majd koaxiális tágítókatétert alkalmazva stent behelyezésére alkalmas introducert vezettünk át a májszöveten. A szűk anasztomózisba nitinol (2 esetben), illetve acél (1 esetben) öntáguló fémstentet helyeztünk. Az introducer eltávolítása közben a parenchymás járatot egy alkalommal embolizációs spirállal, egyszer pedig sebészi szivacsrészecskékkel embolizáltuk. A harmadik esetben embolizáció nem történt. Eredmények: A kezelés mindhárom esetben sikeres volt. A beavatkozással kapcsolatban szövődményt nem észleltünk. Két esetben az indikációt jelentő hasi folyadék mennyiségének csökkenése, egy esetben a nyelőcső-varicositas visszafejlődése jelentette a klinikai kép javulását. Mindhárom esetben ultrahangos és komputeres rétegvizsgálat is igazolta a szűkületek sikeres kezelését. Két beteg a beavatkozás után 10, illetve 39 hónappal jól van. Egy beteget a beavatkozás után egy hónappal többszervi elégtelenség miatt elvesztettünk. Következtetés: A venaportae-anasztomózis szűkületeinek kezelésére a percutan transhepaticus kanülálás és öntáguló fémstent behelyezése biztonságosan és sikeresen alkalmazható.

The role of covered stent in the management of biliary complications is not yet defined in liver transplant recipients. This Case Report presents a patient with anastomotic stricture and leakage with biloma treated with a covered stent 32 months following liver transplantation. Signs of in-stent restenosis developed 52 months following covered stent placement, which was resolved by balloon dilation. There were no complications during the interventions. The latest follow-up, at 69 months following primary and 19 months following secondary percutaneous intervention, shows a patent covered stent without any clinical or morphological sign of further restenosis. The clinical success with long-term follow-up data suggests that covered stent implantation can be a rational, minimally invasive option for simultaneous treatment of bile duct stenosis and bile leak following liver transplantation in selected cases.

Vascular complications are major causes of graft failure in liver transplantation. The use of different vascular grafts is common but the results are controversial. The aim of this study was to create an ‘ideal’ arterial interponate for vascular replacements in the clinical field. An autologous, tubular graft prepared from the posterior rectus fascia sheath was used for iliac artery replacement in dogs for 1, 3, 6 and 12 months. Forty-one grafts were implanted and immunosuppression was used in separate groups. The patency rate was followed by Doppler ultrasound. Thirty-seven grafts remained patent, 2 cases with thrombosis and 2 cases with stenosis occurred. There was no evidence of necrosis or aneurysmatic formation. The histological analysis included conventional light microscopic and immunohistochemical examinations for CD34 and factor VIII. The explanted grafts showed signs of arterialisation, appearance of elastin fibres, and smooth muscle cells after 6 months. Electron microscopy showed intact mitochondrial structures without signs of hypoxia. In conclusion, the autologous graft presents acceptable long-term patency rate. It is easy to handle and the concept of beneficial presence of the anti-clot mesothelium until endothelialisation seems to work. The first clinical use was already reported by our group with more than 2 years survival.

A large, rapidly growing malignant peripheral nerve sheath tumor (MPNST) of the liver in a young female patient, not associated with von Recklinghausen’s disease, is presented. Diagnosis was based on detailed immunohistochemical and electromicroscopic examination beside the characteristic H&E picture. As far as we know, this is the first reported, unambiguously proven “de novo” MPNST in the liver. Differential diagnostic problems are discussed and a review of the literature is given.

Absztrakt Májtranszplantáció után a graft subcapsularis haematomája és/vagy rupturája, mely kialakulhat spontán, sérülés vagy invazív radiológiai beavatkozásokat követően, ritkán előforduló, súlyos szövődmény. Szerzők 350 májátültetés során észlelt négy esetből három ismertetésével illusztrálják a szövődmény súlyosságát. Az első esetben graftbiopszia utáni álaneurysma halálos kimenetelű májrupturát eredményezett. A második esetben a donormáj felszínes sérülésének transzplantáció után mély ruptura lett a következménye, amely miatt májresectiót kellett végezni. A beteg septicus állapotban meghalt. A harmadik beteg műtét során észlelt subcapsularis haematomáját sikeresen kezelték, és a beteg meggyógyult. Eddigi tapasztalataik és az irodalmi ajánlások alapján a szerzők javaslatot fogalmaznak meg a műtét során keletkező májtok alatti vérömlenyek kezelésére, melynek lényegi részét képezi az argon-diathermia és a fibrinogennel és thrombinnal bevont kollagénszivacs alkalmazása.

A májátültetés jelenti a gyermekkori végstádiumú májbetegségek egyetlen kezelési módját. A split, majd az ezt követően kifejlesztett élő donoros májátültetés ma már rutinbeavatkozásnak számít, és a gyermekkori átültetések alapját jelentik. Az átlagos Kaplan–Meier-féle meghatározás szerinti 1, illetve 5 éves túlélés 80–90% feletti. A donormáj splittelése során két májbetegen segíthetünk. A bal oldali laterális szegmenteket általában gyermekeknek, a nagyobb jobb oldalt felnőtteknek ültetjük át. Természetesen többféle kombináció jön szóba attól függően, hogy élő donoros vagy split-, vagy redukált májátültetésről van szó. Az átültetéshez szükséges májszövet mennyisége a testsúly minimum 1%-át jelenti. A hazai több mint 340 májátültetés során 27 gyermek (14 parciális graft) májátültetéséről számolhatunk be, és elindult az élődonor-program is. Az alkalmazott technikák eredményeit és szövődményeit is figyelembe véve elmondható, hogy megfelelően szigorú kivizsgálási protokollok betartásával, a sebészi, aneszteziológiai és intenzív osztályos kezelés megfelelő szintű fejlesztésével a hazai átültetések eredményei nemzetközi szintre emelkedtek. Az utolsó 5 év átlagos túlélése 80% feletti volt.

Background. Cytomegalovirus (CMV) infection in transplant patients with special risk factors remains a major hazard. CMV-seronegative recipients with seropositive donors have the highest risk of developing acute CMV disease. We suggest that the HLA-type may influence the occurrence and the severity of primary CMV infection of these recipients and the measurement of the special HLA-types may be useful in the prediction of acute infection. Methods. Since 1999 1213 cadaver kidney transplantations have been performed in our clinic. 163 of 1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney from seropositive donors. All 129 patients received CMV infection prophylaxis. Of 129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the first posttransplant year. CMV infection was diagnosed by CMV antigenemia test and serologic measurements (ELISA). The particular HLA-genotypes of the recipients were studied before the transplantation. The occurrence and the severity of CMV infection was investigated in association with HLA-types. Results. We found different acute CMV infection distribution in the careers and non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA-DR11, but the differences weren't significant in these HLA-types (P = 0.26, P = 0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%) had acute CMV infection and this difference was found to be significant. This result was confirmed by univariate and multivariate Cox Regression (P = 0.001) and the appropriate significance level was considered by Bonferroni correction. Conclusions. HLA-DQ3 was found to be an independent predictor of CMV infection. Our data suggest that patients positive for HLA-DQ3 are more susceptible to CMV infection than a comparable group of patients negative for HLA-DQ3. This result was not due to rejection and/or treatment for rejection and wasn't influenced by induction therapy. Although we found more symptomatic infections among DQ3+ patients the difference wasn't significant (P = 0.19). Comparing the gender proportion among all 1213 kidney recipients and among CMV-seronegative recipients we found that the proportion of males is significantly higher among CMV-seronegative recipients (P < 0.001).

A szerzők elemzik a HBV-fertőzés miatt végzett májátültetés hazai tapasztalatait, áttekintik a HBV okozta májbetegség transzplantáció szempontjából sajátos pre- és posztoperatív kezelési igényeit. A transzplantációs program során 2006. december 31-ig 4 betegnél történt HBV-fertőzés talaján kialakult végstádiumú májbetegség miatt májátültetés. Közülük 1 beteget veszítettek el a korai posztoperatív időszakban, 3 beteg él, aktív. Elemzik a transzplantációt követően 6 esetben észlelt de novo HBV-fertőzést és annak hatását a betegek túlélésére.

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.

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.

Introduction: The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. Aim: The aim of this study was to analyse risk factors and colonisations of bacterial infections. Method: The files of 408 patients (281 bacterium cultures) were reviewed. Results: Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonal infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p

Authors analyzed the differences in the outcome of two European liver transplant centers differing in case volume and experience. The first was the Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary (SEB) and the second the University Medical Center Groningen, Groningen, The Netherlands (UMCG). We investigated if such differences could be explained. The 1-, 3- and 5-year patient survival in the UMCG was 86%, 80%, and 77% compared with 65%, 56%, and 55% in SEB. Graft survival at the same time points was 79%, 71%, and 66% in the UMCG and 62%, 55%, and 53% in SEB. Significant differences were present regarding the donor and recipient age, diagnosis mix, disease severity and operation variables, per-operative transfusion rate, vascular complications, postoperative infection rate, and need for renal replacement. To determine factors correlating with survival, a separate uni- and multivariate analysis was performed in each center individually, between study parameters and patient survival. In both centers, peri-operative red blood cell (RBC) transfusion rate was a significant predictor for patient survival. The difference in blood loss can be explained by different operation techniques and shorter operation time in SEB, with consequently less time spent on hemostasis. It was jointly concluded that measures to reduce blood loss by adapting the operation technique might lead to improved survival and reduced morbidity.

Background: Liver transplantation for hepatic tumours is known as a proven treatment opportunity. The outcome has improved over the past decades because of the appropriate recipient selection. Materials and methods: In a single-institution study of 29 consecutive adult patients underwent orthotopic liver transplantation (OLT) between 1 January 2004 and 1 January 2011 in the Semmelweis University, Budapest with the indication of hepatocellular carcinoma (HCC). Results: The 1-year survival was 85.7% and the 3-year survival was 71.7%. Conclusions: Further investigations are needed on the field of histological and biological attributes of the hepatocellular carcinoma. Our aim is to find a better and individualized immunosuppressive protocol, which is also protective against malignant tumours

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.

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.

Hepatic diseases decrease the liver's involvement in thermoregulation. Removal of the liver during transplantation increases the incidence of hypothermia during the surgery. The aims of the present study were to analyze the hemodynamic changes among hypothermic liver transplantations and to determine its relationship to postoperative complications.Conventional and volumetric hemodynamic monitoring and intramucosal pH measurements were performed during 54 liver transplantations. According to the core temperature until graft reperfusion, patients were classified into group A, hypothermic patients (temperature35 °C; n=25) versus group B, normothermic patients (temperature36 °C; n=29). We examined the relationships between central venous pressure (CVP), intrathoracic blood volume index, cardiac index (CI), and oxygen delivery index, oxygen consumption index, as well as the fluctuation of the mean arterial pressure (MAP) and gastric intramucosal pH and activated clotting time. We recorded prolonged ventilation time, vasopressor and hemodialysis requirements, occurrence of infections, and intensive care days.There were no significant differences in the MELD scores. More Child-Pugh class C patients (P.01) showed significantly higher APACHE II scores (P.02) among group A. During hepatectomy and at the same intrathoracic blood volumes, the hypothermic group showed significantly higher CVP levels (P.02). During the anhepatic and postreperfusion phases, the decreased CI levels (P.05) were associated with increased MAP values (P.05). Without differences in oxygen delivery, the oxygen consumption was lower in group A (P.05). The intramucosal pH levels were the same in the both groups during the whole examination period. More instances of infection, intensive care, and hemodialysis treatment days, were observed as well as significantly longer vasopressor requirements and coagulopathy among the hypothermic group (P.007).

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.

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 β-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.