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Összefoglaló. Bevezetés: A májtranszplantációs program részeként 1995 óta létezik folyamatosan vezetett várólista Magyarországon. Célkitűzés: A legfontosabb várólista-paraméterek megállapítása és nemzetközi összehasonlítása. Módszer: A szerzők az 1995. január 1. és 2019. december 31. között első májátültetés céljából várólistára helyezett betegek adatait elemezték. Eredmények: Összesen 1722 beteget helyeztek várólistára, 1608 felnőttet, 114 gyermeket. A férfiak aránya 51,2%, az átlagéletkor 45,6 év. Az évente regisztrált új jelöltek száma 25 év során közel az ötszörösére emelkedett. A listára helyezés leggyakoribb indikációja a víruseredetű cirrhosis volt (n = 451). Ezt követte a cholestaticus (n = 314) és az alkoholos májbetegség (n = 264). Rosszindulatú daganat, 82%-ban hepatocellularis carcinoma miatt 215 beteget regisztráltak. Krónikus betegségekben az átlagos Model for End-Stage Liver Disease pontszám a regisztráláskor 13,5 volt. A 2018. december 31-ig listára helyezettek (n = 1618) 61%-a részesült májátültetésben, 24%-a várakozás közben meghalt, 7%-a a műtétre alkalmatlanná vált. A műtét előtti medián várakozási idő 248 nap volt a krónikus és 2 nap az akut betegek listáján. A transzplantált tumoros betegek (n = 132) szignifikánsan rövidebb ideig vártak műtétre (medián 115,5 nap), mint a többi krónikus beteg (n = 803, medián 282 nap). Az Eurotransplanthoz való csatlakozás utáni időszakban (2013. július 1. és 2018. december 31. között) a transzplantációs arány növekedett (67%), a várólista-halálozás (meghaltak + műtétre alkalmatlanná váltak) 24%-ra csökkent. Megbeszélés: A várólista folyamatos bővülése hozzájárult a hazai májátültetési program fejlődéséhez. A hazai várólista diagnózis szerinti összetétele a mások által közöltekkel nagyrészt egyezik. A transzplantáltak aránya a nemzetközi átlagnak megfelelő. A várólista-halálozás és a műtét előtti várakozási idő a magyarországinál alacsonyabb donációs aktivitású vagy jelentősen nagyobb várólistával rendelkező országokéhoz hasonló. Következtetés: Várólista-paramétereink javításához a transzplantációk számának további növelése szükséges. Orv Hetil. 2022; 163(8): 301–311. Summary. Introduction: The Hungarian liver transplant program including waiting list started in 1995. Objective: Evaluation of the wait-list parameters and comparing them with those in the literature. Method: Data of patients listed for primary liver transplantation between 1995 and 2019 were analyzed. Results: A total of 1722 recipient candidates were registered on the liver transplant waiting list: 1608 adults (51.2% men) with mean age of 45.6 year and 114 patients aged versus 282 days). Discussion: The composition of our waiting list by primary liver disease was similar to that of countries with large burden of hepatitis C. Transplant rate was average, wait-list mortality and waiting time were in line with those observed in low-donation countries or in the case of large volume waiting list. Conclusion: Listing of increasing the number of patients contributed to evolution of our liver transplant program. To improve our parameters, increasing transplant activity is warranted. Orv Hetil. 2022; 163(8): 301–311.

Hepatocellular carcinoma (HCC) is the leading primary liver tumor and a main indication for transplant. Transplant criteria are based on clinicopathologic features, meanwhile adequate downstaging and molecular mechanisms are getting more attention in evolving therapeutic algorithm of HCC. The aim of our study was to overview the results of the Hungarian Liver Transplant Program in the field of HCC and introduce new aspects of personalized treatment options.We performed retrospective analysis of survival and tumor recurrence of HCC-associated liver transplant recipients between October 2013 and December 2020. Patients were categorized in Milan criteria (MC), beyond MC but within University of California, San Francisco (UCSF), and beyond UCSF criteria groups after pathologic examination of the explanted liver. Demographic data and preoperative locoregional treatments were assessed.A total of 529 primer liver transplants were performed, 88 because of HCC. A total of 87 patients had underlying cirrhosis because of hepatitis C (54%), alcohol-related liver disease (33.7%), hepatitis B (4.5%), or unknown etiology. A total of 55.6% of the patients had at least one locoregional treatment. A total of 67.4% of the patients were within MC, 5.6% were within UCSF criteria, and 27% were beyond UCSF criteria. The 1-, 3-, and 5-year survival rates were 80%, 79%, and 75%. The outcome was better in early-stage tumors, but the difference was not significant (P = .745) CONCLUSIONS: The favorable survival in our department legitimates the strict transplant criteria of HCC. Adequate locoregional therapy as downstaging can expand recipient pool. Molecular tumor profiling may lead to personalized treatment of HCC.

In hepatocellular carcinomas (HCCs), the role of the cell surface protein V-set and immunoglobulin domain containing 1 (VSIG1), which is known as a specific marker of the gastric mucosa and testis, has not yet been determined. We examined VSIG1 immunohistochemical (IHC) expression in 105 consecutive samples provided by HCC patients, along with the IHC expression of three of the biomarkers known to be involved in the epithelial–mesenchymal transition (EMT): vimentin (VIM), and E- and N-cadherin (encoded by CDH1 and CDH2 genes). IHC subcellular localization of thyroid transcription factor 1 (TTF1), in which nuclear-to-cytoplasmic translocation is known to cause a lineage shift from lung to gastric-type adenocarcinoma, was also checked. The obtained data were validated using the miRNET program. In the examined HCC samples, VSIG1 expression was observed in the cytoplasm of normal hepatocytes and downregulated in 47 of the 105 HCCs (44.76%). In 29 cases (27.62%), VSIG1 was co-expressed with cytoplasmic TTF1. VSIG1 expression was positively correlated with both E-cadherin and N-cadherin and negatively correlated with VIM (p

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.

Background End-stage renal disease is an irreversible status of kidney dysfunction that reduces both renal and non-renal drug clearance. Accumulation of uremic toxins seems to modify the activities of drug-metabolizing cytochrome P450 (CYP) enzymes. The aim of the present work was to refine gene expression analysis for efficient and accurate quantification of CYP mRNAs in patients’ leukocytes. Methods We compared six liquid–liquid extraction reagents for RNA isolation and five reverse transcriptase kits for RNA-to-cDNA conversion, and developed quantitative polymerase chain reaction methods for duplex measurements of CYP target genes and the reference gene. The expression of CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in patients with end-stage kidney disease (N = 105) and in organ donors with healthy kidney function (N = 110) was compared. Results Regarding the RNA yield and purity, TRIzol, Trizolate and TRI reagents were equal; however, TRI reagent was the most advantageous in terms of financial cost. Reverse transcription using Maxima First Strand cDNA Synthesis kit appeared to be the most efficient with the widest range for quantification of the target transcript. The refined method with the detection of various CYPs and the reference gene in duplex PCR efficiently quantified even the low-level CYP expression. In leukocytes of patients with end-stage renal disease, all four CYPs were expressed at significantly lower level than in organ donors with normal kidney function (p Conclusions Reduced CYP expression was a direct evidence of transcriptional down-regulation of CYP genes in patients with impaired kidney function.

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.

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.

Due to the COVID-19 pandemic caused by infection with the novel, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transplant medicine also had to face a new, hitherto unknown challenge. To be prepared for any possibility, we consider it important to summarize the current knowledge regarding COVID-19 of liver and kidney transplant patients. Very early reports from Spanish and French registry recorded fatality rates of 18.6% and 13%, respectively, in renal patients which suggests a moderately worse outcome compared to the general population. In patients with positive PCR test but not showing clinical signs, the reduction of immunosuppression is not advised. In the case of gastrointestinal or respiratory signs with fever, the discontinuation of mycophenolate or mTOR inhibitors is recommended with decrease of the trough levels of calcineurin inhibitors to the lowest effective limit. Stop (kidney transplanted patients) or decrease (liver transplanted patients) immunosuppression and maintain corticosteroids when pulmonal injury develops and consider anti-IL1 and anti-IL6 monoclonal antibody use when hyperinflammatory syndrome is evolving. No proven effective treatment for SARS-CoV-2 exists currently. The use of lopinavir/ritonavir should be avoided because of the severe drug interaction with calcineurin inhibitors. The efficacy and tolerability of hidroxychloroquin remains to be also questionable; enroll patients into clinical trial with remdesivir or favipiravir if available. COVID-19 is characterized by virus-induced endothelial dysfunction, procoagulant state and renin-angiotensin-aldosteron system imbalance. Early thromboprofilaxis combination with low-molecular-weight heparin and low-dose aspirin is strongly recommended with the maintenance of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-II-receptor blocker (ARB) therapy when they were prescribed earlier. Orv Hetil. 2020; 161(32): 1310-1321.

International data indicate that arterial, venous and microvascular thrombosis or disseminated intravascular coagulation occur in more than 30% of hospitalized patients with COVID-19. This condition is characterized by high levels of D-dimer and fibrinogen, prolonged prothrombin time and activated partial thromboplastin time.Blood samples from three COVID-19 patients treated in a Hungarian intensive care unit were collected and analyzed with ClotPro® tests. EX-tests, IN-test, FIB-tests, RVV-tests, and TPA-tests were performed. The results were interpreted with respect to the clinical condition of the patients.Procoagulation, hypercoagulation and either fibrinolysis or a "shut down" phenomenon of the fibrinolytic process were found with ClotPro®. The ClotPro® parameters were consistent with the conventional coagulation tests and corresponded with the criteria of non-overt disseminated intravascular coagulation.These findings encourage further investigations to elucidate the underlying pathophysiology of thromboembolic events in COVID-19 patients and may support the introduction of full dose anticoagulation with or without antiplatelet therapy. Interventional clinical trials may be helpful in defining the appropriate drug(s), for this purpose, the algorithms of administration, and the optimal duration of therapy. At present, the authorization of a clinical trial that attempts to answer these questions is in progress. Orv Hetil. 2020; 161(22): 899-907.

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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.

The most common benign liver tumours are haemangiomas, focal nodular hyperplasia and hepatocellular adenoma. We perform a review of the literature and show the current diagnostic and therapeutic modalities based on the EASL Clinical Practice Guideline. With the widespread use of ultrasound, the detection of liver lesions is increased. They are usually found in women of childbearing age with atypical abdominal pain or incidentally. Contrast-enhanced US, CT or MRI are usually necessary for differential diagnosis. In atypical appearance or in malignancy suspect cases biopsy could be performed. For symptomatic patients conservative therapy can be sufficient. In haemorrhagic cases transarterial embolisation can be useful, also for tumour size decreasing before surgery. In patients with persisting symptoms, with vessel or soft tissue compression effect or in malignancy suspect cases definitive surgical treatment is advised. In men with hepatocellular adenoma primary resection is appropriate because of the higher risk for malignant transformation. As alternative treatment options radiofrequency ablation, irradiation, chemotherapy, monoclonal antibody therapy or liver transplantation are published.A jóindulatú májdaganatok leggyakoribb formái a hemangióma, a fokális noduláris hiperplázia és a májadenóma. Célunk az EASL Clinical Practice Guidelines és a szakirodalom áttekintése alapján a jóindulatú májdaganatok korszerû diagnosztikájának és ellátásának bemutatása. A széles körben elterjedt rutin képalkotó vizsgálatok használatával jelentõsen megemelkedett a felismert benignus elváltozások száma. Általában atípusos hasi fájdalom kivizsgálása során vagy mellékleletként kerülnek felismerésre. Túlnyomó többségben 30–40 év körüli nõket érintenek. Végleges diagnózis legnagyobb eséllyel kontrasztanyagos MR-vizsgálattal nyerhetõ, további bizonytalan megjelenés, nem kizárható malignitás esetén szövettani mintavétel lehet indokolt. Klinikai relevanciája a panaszt okozó, vérzéses szövõdménnyel vagy nyomási tünetekkel járó, valamint a malignus transzformációt mutató eseteknek van, mely fõképp a férfiaknál elõforduló béta-katenin-pozitív adenómára jellemzõ, hemangiómánál és FNH-nál nem ismert. Kezelésében a konzervatív tüneti ellátás és betegkövetés, radiológiai intervenció, onkológiai kezelés is helyet kaphat, végleges megoldás sebészi úton nyerhetõ.

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.

Bidirectional interaction between immune and nervous systems is considered an important biological process in health and disease. However, little is known about the mechanisms involved in their interaction in the human liver. This study examines the distribution of intrahepatic NPY, SP immunoreactive (IR) nerve fibers and their antomical relationship with immunocells containing tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB) in patients with autoimmune hepatitis. Liver specimens were obtained from control liver and autoimmune hepatitis patients. The immunoreactivity was determined by immunohisto- and immunocytochemistry and confocal laser microscopy. In hepatitis, the number of NPY-IR and SP-IR nerve fibers increased significantly. These IR nerve fibers were in very close contact with the lymphocytes. In healthy controls, no NPY-IR, SP-IR or NF-κB IR lymphocytes and only a few TNF-α positive cells, were observed. In hepatitis, some of the lymphocytes showed immunoreactivity for SP and NPY in the portal area. Fluorescent double-labeled immunostaining revealed that in these cells NPY did not colocalize with TNF-α or NF-κB. However, some of the SP fluorescence-positive immune cells exhibited immunostaining for p65 of NF-κB, where their labeling was detected in the nuclei. Under the electronmicroscope, these cells could be identified (lymphocytes, plasmacells and mast cells). The gap between the IR nerve fibers and immunocells was 1 μm or even less. Overexpression of SP in lymphocytes may amplify local inflammation, while NPY may contribute to liver homeostasis in hepatitis. Neural immunomodulation (SP antagonists and NPY) might be a novel therapeutic concept in the management of liver inflammation.

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.

Many undesired side effects or therapeutic failures of drugs are the result of differences or changes in drug metabolism, primarily depending on the levels and activities of cytochrome P450 (P450) enzymes. To assess whether P450 expression profiles can reflect hepatic drug metabolism, we compared P450 mRNA levels in the liver or peripheral leukocytes with the corresponding hepatic P450 activities. A preliminary P450 genotyping for the most frequent polymorphisms in white populations (CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, CYP2D6*6, and CYP3A5*3) was carried out before P450 phenotyping, excluding the donors with nonfunctional alleles of CYP2C9, CYP2C19, and CYP2D6 and those with a functional CYP3A5*1 allele from a correlation analysis. The hepatic mRNA levels of CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 displayed a strong association with P450 activities in the liver, whereas the expression of CYP1A2, CYP2C9, CYP2C19, and CYP3A4 in leukocytes was proven to reflect the hepatic activities of these P450 species. The leukocytes were found to be inappropriate cells for the assessment of hepatic CYP2B6 and CYP2D6 activities. Combining the results of P450 genotyping and phenotyping analyses, patients' drug-metabolizing capacities can be estimated by the P450 expression in the liver and in leukocytes with some limitations. Patients' genetic and nongenetic variations in P450 status can guide the appropriate selection of drugs and the optimal dose, minimizing the risk of harmful side effects and ensuring a successful outcome of drug therapy.

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 májátültetések számát korlátozza a beültetésre alkalmas donorszervek mennyisége. A szervhiány megoldására az egyik lehetőség az úgynevezett marginális donorok (extended donor criteria) elfogadása a májátültetési programban.Célkitűzés:A magyar májátültetési program szervdonációs jellemzőinek vizsgálata, különös tekintettel a marginális donorokra.Módszer:Donor- és recipiensadatok retrospektív feldolgozása 2003. január és 2008. december között. A marginálisdonor-kritériumrendszert nemzetközi ajánlások alapján állítottuk fel.Eredmények:A vizsgált periódus alatt összesen 1078 donort jelentettek a klinikán. Nyolcszázharmincöt esetben (77,4%) alkalmatlannak ítélték a donormájat a transzplantációra, 243 esetben (22,6%) volt beültetésre alkalmas a donormáj. A beültetett májgraftok közül 40 (16%) származott marginális, 203 (84%) nem marginális donorból. Marginális májgraftok beültetése esetén nem volt különbség a beteg- és grafttúlélésben, a posztoperatív graftfunkciót jelző paraméterekben és az általános szövődmények gyakoriságában. A korai hepatitis C-rekurrencia gyakoribb volt marginális graft beültetése esetén.Következtetések:A májátültetésre váró betegek száma hazánkban is folyamatosan növekszik. Marginális májgraftok alkalmazása esetén a betegek morbiditása és mortalitása nem különbözik számottevően a standard donorokból származó májgraftok beültetése után tapasztalt eredményektől. Hepatitis C-vírus esetén nem javasolt marginális májgraft beültetése. A donorok felső életkori határának kiterjesztése megfontolandó.