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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: 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 Within the last decade numerous attempts have been reported in order to expand the donor pool and alleviate organ shortage in the setting of liver transplantation. Aim of this blinded randomized controlled trial was to evaluate the effect of donor steroid pretreatment on outcomes after liver transplantation. Methods We performed an international, multi-center double-blinded randomized placebo controlled trial. Donors received 1000 mg methylprednisone or placebo before organ procurement. Primary endpoint were patient and graft survival. Secondary end points were rate of BPAR and liver functions trajectories after transplantation. Follow up was 10 years. Results There was no effect of steroid pretreatment vs. placebo on overall patient survival (50% vs. 46%, p = n.s.) as well as graft survival (47% vs. 51%, p= n.s.). Further donor steroid pretreatment did not alter the rate of biopsy proven acute rejections (34% steroid group vs. 36% placebo, p = n.s.). Evaluating short term and long term graft function, steroid pretreatment had minor effect on immediate liver function trajectories within the first 2 weeks after transplantation. This was not seen in long-term follow up. Conclusion In conclusion we found no evidence that donor steroid pretreatment translates in improved outcomes after liver transplantation.

Unresectable liver metastases of gastroenteropancreatic neuroendocrine tumors are an accepted indication for liver transplant. Patients undergoing liver transplant because of neuroendocrine tumor liver metastases have similar long-term survival compared with hepatocellular carcinoma; however, recurrence rates are reported to be higher. Methods We performed a retrospective analysis of medical records of patients who received transplants for neuroendocrine tumor liver metastases in the Department of Transplantation and Surgery of Semmelweis University between January 1995 and August 2018. The median follow-up period was 33 months. Results Ten liver transplants have been performed because of neuroendocrine tumor liver metastases during the observed period. Recurrence occurred in 5 cases, and 3 patients died. Estimated 1- and 5-year patient survival rates after transplant were 89% and 71%, respectively. Estimated 1- and 5-year recurrence-free rates were 80% and 43%, respectively. Every patient whose primary tumor was of pancreatic origin or those recipients who had Ki67 index values in the explanted liver higher than 5% had disease recurrence. Conclusion Patient survival and recurrence rates after liver transplant were comparable with the results reported by other centers. In line with previous findings, primary pancreatic neuroendocrine tumors and higher Ki67 index values in the explanted livers were both associated with higher recurrence rates. We believe that an international registry would be helpful to better understand factors leading to tumor recurrence in these cases.

Diagnosis and treatment of hepatitis B virus (HBV) and hepatitis D virus infection mean for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms from 22 September 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0,5–0,7%. The indications of treatment are based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for a cost-effective approach, the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard as well as the relevance of appropriate consistent follow-up schedule for viral response during therapy. The first choice of therapy in chronic HBV infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Lamivudine is no longer the first choice; patients currently taking lamivudine must switch if the response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv Hetil. 2018; 159(Suppl 1): 24–37.

Reduced baroreflex sensitivity (BRS) is a frequent complication in end-stage liver disease, but the underlying mechanism is unknown. We investigated the mechanical and neural components of BRS. Increased nitric oxide (NO) production has been reported in end-stage liver failure. Based on earlier experiments, we hypothesised that enhanced endothelial function might affect baroreflex function. Therefore, we explored the relation between endothelial function and the components of BRS.We enrolled 24 patients and 23 controls. BRS was determined by the spontaneous sequence method. Mechanical component was characterised by the distensibility coefficient (DC) of common carotid artery. Neural component was estimated as the ratio of integrated BRS and DC. Endothelial function was quantified by flow-mediated dilation (FMD) of the brachial artery.Integrated BRS was reduced in patients [7.00 (5.80-9.25) vs. 11.1 (8.50-14.80) ms/mmHg]. The mechanical component was not different in the two groups, whereas neural component showed significant reduction in patients (3.54 ± 1.20 vs. 4.48 ± 1.43 ms/10Baroreflex impairment in end-stage liver disease might be explained by deterioration of the neural component, while the mechanical component appears to be preserved. Endothelial NO may enhance BRS in health; however, central endothelial overproduction of NO likely contributes to the reduction of neural component of BRS in patients awaiting liver transplantation.

Treatment of hepatitis C is based on a national consensus guideline updated six-monthly according to local availability and affordability of approved therapies through a transparent allocation system in Hungary. This updated guideline incorporates some special new aspects, including recommendations for screening, diagnostics, use and allocation of novel direct acting antiviral agents. Indication of therapy in patients with no contraindication is based on demonstration of viral replication with consequent inflammation and/or fibrosis in the liver. Non-invasive methods (elastographies and biochemical methods) are preferred for liver fibrosis staging. The budget allocated for these patients is limited. Therefore, expensive novel direct acting antiviral combinations as first line treatment are reimbursed only, if the freely available, but less effective and more toxic pegylated interferon plus ribavirin dual therapy deemed to prone high chance of adverse events and/or low chance of cure. Priority is given to those with urgent need based on a pre-defined scoring system reflecting mainly the stage of the liver disease, but considering also additional factors, i.e., hepatic decompensation, other complications, activity and progression of liver disease, risk of transmission and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virological response value in different patient categories with consensus amongst treating physicians, the National Health Insurance Fund and patient’s organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv. Hetil., 2017, 158(Suppl. 1), 3–22.

Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5–0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2017, 158(Suppl. 1) 23–35.

Introduction Transplant hepatologists convened in Warsaw on 20-21 November 2015 at a meeting of the Initiative Group for Central European Hepatologic Collaboration to exchange their experience in liver transplantation in their respective countries. Material and methods The description is based on narration of individual country representatives, supplemented by data from additional queries, and from publicly accessible sources. Results Liver transplantation programs were launched, in the Czech Republic in 1983, in Poland in 1990 (paediatric) followed by the adult program 1994; the first liver transplant in Hungary was performed in 1995, with Slovakia launching its liver transplantation program in 2008. Currently, there are 2 centres for liver transplantation in Slovakia, 1 centre in Hungary, 6 centres in Poland, and 2 centres in the Czech Republic. The rates of liver transplantation correspond to the number of cadaveric donations being the highest in the Czech Republic (15.8 per million population) and the lowest in Slovakia (4.2 per million population) (2014 data). Live donation is utilized systematically in Poland. Indications vary from country to country, but the 3 most frequent ones include hepatitis C and B cirrhosis, alcoholic cirrhosis, and cholestatic liver disorders. There is a growing incidence of hepatocellular carcinoma among adult liver transplant recipients. Biliary atresia and hereditary diseases are the most frequent indications among children. Hungary became a member of Eurotransplant, other countries are not a part of any international organization for organ sharing. Conclusions Despite some differences, liver transplant programs seem to be compatible honouring the same values and principles universal to liver transplant programs in most parts of the world.

Approximately 70.000 people are infected with hepatitis C virus in Hungary, more than half of whom are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy on one hand. From socioeconomic aspect, this could also prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity. Available since 2003 in Hungary, pegylated interferon + ribavirin dual therapy can clear the virus in 40–45% of previously not treated (naïve), and in 5–21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained virologic response to 63–75% and 59–66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antiviral interferon-free combination therapies have been registered for the treatment of chronic hepatitis C, with a potential efficacy over 90% and typical short duration of 8–12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and or fibrosis in the liver. Non-invasive methods (eleastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations tharpy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained virologic response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(Suppl. 2), 3–24.

Available data on the prevalence of hepatic steatosis in an unselected HIV-infected population are limited. The aim of this study was to determine the prevalence of hepatic steatosis and assess the associated factors in HIV-infected individuals.One hundred and thirty-six HIV-infected individuals were enrolled in this cross-sectional study. Patients underwent transient elastography and controlled attenuation parameter (CAP) measurements. We analyzed the associations between the CAP value and demographic, metabolic, and immunologic parameters. For the first time, in HIV-infected individuals, we used a continuous scale of CAP values to identify significant covariates of hepatic fat accumulation. As a result and compared with other methods, one of the main advantages of CAP was that the quantitative measurement of liver steatosis could be used for analysis.Using univariate analysis, CAP was significantly correlated with the following continuous variables: CD4 percentage (P=0.035), CD8 percentage (P=0.016), age (P0.001), CD4/8 ratio (P=0.002), BMI (P0.001), serum triglyceride (P0.001), and serum cholesterol (P=0.004) levels, the length of known HIV positivity (P0.001), and liver stiffness (P=0.041). With respect to categorical variables, a significant association was found for the presence of diabetes (P=0.006), hypertension (P0.001), facial lipodystrophy (P=0.031), and the use of lopinavir (P=0.042). In multivariate analysis using linear regression, BMI (P0.001), presence of diabetes (P=0.026), and hypertension (P=0.040) were identified as independent significant correlates. Darunavir therapy was associated negatively with the CAP value (P=0.032).Our findings reflect the importance of metabolic factors in hepatic steatosis. The strongest independent covariate was BMI.

Diagnosis and treatment of hepatitis B and D virus infections mean that the patient is able to maintain working capacity, increase quality of life, prevent cancer, and prolong life expectancy, while the society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2015, which is agreed on a consensus meeting of specialists involved in the treatment of the above diseases. The prevalence of hepatitis B virus infection in the Hungarian general population is 0.5–0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline emphasizes the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2015, 156(Suppl. 1), 25–35.

Approximately 70,000 people are infected with hepatitis C virus in Hungary, and more than half of them are not aware of their infection. From the point of infected individuals early recognition and effective treatment of related liver injury may prevent consequent advanced liver diseases and complications (liver cirrhosis, liver failure and liver cancer) and can increase work productivity and life expectancy. Furthermore, these could from prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity, as a socioeconomic aspect. Pegylated interferon + ribavirin dual therapy, which is available in Hungary since 2003, can clear the virus in 40–45% of previously not treated (naïve), and in 5–21% of previous treatment-failure patients. Addition of a direct acting first generation protease inhibitor drug (boceprevir or telaprevir) to the dual therapy increases the chance of sustained viral response to 63–75% and 59–66%, respectively. These two protease inhibitors are available and financed for a segment of Hungarian patients since May 2013. Between 2013 and February 2015, other direct acting antivirals and interferon-free combination therapies have been registered for the treatment of chronic hepatitis C with a potential efficacy over 90% and typically with a short duration of 8–12 weeks. Indication of therapy includes exclusion of contraindications to the drugs and demonstration of viral replication with consequent liver injury, i.e., inflammation and/or fibrosis in the liver. Non-invasive methods (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment accurate and timely molecular biology tests are mandatory. Eligibility for treatment is a subject of individual central medical review. Due to budget limitations therapy is covered only for a proportion of patients by the National Health Insurance Fund. Priority is given to those with urgent need based on a Hungarian Priority Index system reflecting primarily the stage of liver disease, and considering also additional factors, i.e., activity and progression of liver disease, predictive factors of treatment and other special issues. Approved treatments are restricted to the most cost-effective combinations based on the cost per sustained viral response value in different patient categories with consensus between professional organizations, National Health Insurance Fund and patient organizations. More expensive therapies might be available upon co-financing by the patient or a third party. Interferon-free treatments and shorter therapy durations preferred as much as financially feasible. A separate budget is allocated to cover interferon-free treatments for the most-in-need interferon ineligible/intolerant patients, and for those who have no more interferon-based therapy option. Orv. Hetil., 2015, 156(9), 343–351.

Aim of the study Combination of ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3DDA±RBV) therapy is shown to be effective in HCV genotype 1 (GT1) infected patients. However, sparse data exist in patients who failed previous boceprevir or telaprevir based therapies. Real life efficacy and safety of this combination were evaluated in HCV GT1b infected patients (mostly cirrhotics) with compensated liver disease who failed previous boceprevir or telaprevir based therapies more than a year before. Material and methods Data of previous protease inhibitor failure patients, treated with 3DAA+RBV for 12 weeks (GT1b and/or non-cirrhotics) or 24 weeks (non-GT1b cirrhotics), were retrospectively collected. Results Population characteristics: boceprevir/telaprevir-failure: 82/45, GT1b: 117, cirrhotic: 111 (87.4%). SVR12/24 was observed in 103/105 patients (98.1%) of those who reached either time point. Four SAEs reported: one death due to myocardial infarction, another due to recurrent hepatocellular carcinoma after achieving SVR12, two hospitalizations (elevation of transaminases, pneumonia). Grade ≥ 3 AEs or laboratory abnormalities were reported in < 10% of patients; they were transient in all patients. No early discontinuation of drugs due to SAE has been reported. Conclusions One year after previous failure of boceprevir or telaprevir based therapy, 12 weeks of 3DAA+RBV combination in HCV GT1b infected patients is similarly effective and safe as in those with no previous HCV therapy, even in the presence of cirrhosis. These findings might be of particular interest in settings where alternative therapies for such patients are not available or not affordable.

Direct-acting antiviral agents have revolutionized hepatitis C therapy, and are also found to be effective in the liver transplant setting. The extent of liver fibrosis influences patient management and is used to monitor therapeutic effects. Shear-wave elastography (SWE) is a relatively new imaging-based method that has not yet been studied extensively in liver transplant patients. Our aim was to study the effect of direct-acting antivirals in heaptitis C recurrence on liver stiffness determined by SWE.A total of 23 liver transplant patients with hepatitis C recurrence were enrolled in this prospective study. The patients underwent 24 weeks of ombitasvir/paritaprevir/ritonavir+dasabuvir±ribavirin combination therapy. Elastographic examinations, serological tests and laboratory tests were performed, and serum biomarkers of liver fibrosis were calculated the day before treatment (baseline) and at the end of the treatment.All our patients became hepatitis C virus RNA negative by the end of the treatment. Median liver stiffness values decreased significantly after treatment compared with baseline (8.72±3.77 vs. 7.19±2.4 kPa; P0.001). Among the studied laboratory values, a significant decrease was observed in the levels of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase, whereas international normalized ratio levels increased. Serum biomarkers, namely aspartate aminotransferase-to-platelet ratio index and Fibrosis-4, decreased significantly after treatment compared with baseline.In the present study, SWE was succesfully used to monitor the beneficial therapeutic effects of direct-acting antivirals in hepatitis C recurrence following liver transplantation. We believe that SWE is a useful noninvasive diagnostic tool in the follow-up of hepatitis C treatment in liver transplant patients.

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.

Background and Aim Management of hepatitis C virus (HCV) recurrence is a major challenge after liver transplantation. Significant dysregulated expression of HCV receptors (i.e. claudin-1, occludin, tetraspanin CD81, scavenger receptor type B1) has been shown recently during HCV infection. This might facilitate hepatocytic entry and reinfection of HCV. MicroRNAs (miRs) play role in the regulation of gene expression. We aimed to characterize miR expression profiles related to HCV infection and antiviral therapy in adult liver transplant recipients, with special emphasis on miRs predicted to target HCV receptors. Methods Twenty-eight adult liver transplant recipients were enrolled in the study. Paired biopsies were obtained at the time of HCV recurrence and at the end of antiviral treatment. MiRs for HCV receptors were selected using target prediction software. Expression levels of miR-21, miR-23a miR-34a, miR-96, miR-99a*, miR-122, miR-125b, miR-181a-2*, miR-194, miR-195, miR-217, miR-221, and miR-224 were determined by reverse transcription–quantitative polymerase chain reaction. Results miR-99a* and miR-224 expressions were increased in HCV recurrence samples, while miR-21 and miR-194 were decreased in comparison to normal liver tissue. Increased expressions of miR-221, miR-224, and miR-217 were observed in samples taken after antiviral therapy when compared with HCV recurrence samples. High HCV titer at recurrence was associated with higher level of miR-122. Conclusions Samples at recurrence of HCV and after antiviral therapy revealed distinct HCV-related miR expression profiles, with significant dysregulation of those miRNAs potentially targeting mRNAs of HCV receptors. In particular, miR-194 and miR-21 might be involved in the regulation of HCV receptor proteins' expression during HCV infection and antiviral therapy.

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.

Background & Aims Brain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function, which might be counterbalanced by steroid pretreatment of the organ donor. The aim of this randomized controlled trial was to elucidate whether steroid pretreatment of liver donors improves early liver allograft function, prevents rejection and prolongs survival. Methods A placebo-controlled blinded randomized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008. Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6 h before recovery of organs. The primary end point was the concentration slope of transaminases within the first week. The secondary end point included survival and biopsy-confirmed acute rejection (BCAR) within 3 years after transplantation. Results Of the 90 randomized donors, 83 recipients were eligible for study. The trajectories of ALT and AST were not different between treatments (p = 0.40 and p = 0.13, respectively). Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment (RR = 0.63 95% CI [0.29, 1.36], p = 0.31). Eleven recipients experienced biopsy-confirmed rejection (BCAR) in the steroid and 11 in the placebo group (RR = 1.02 95% CI [0.50, 2.10], p = 1.00). No effect modification could be identified in the predefined strata of donor age, sex, cold ischemic time, and cause of donor death. Conclusions Steroid pretreatment of organ donors did not improve outcomes after liver transplantation.

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.

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.

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 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.

Selecting suitable candidates for liver transplantation is the most challenging task of pre-transplant evaluation. In addition to somatic assessment, psychosocial evaluation has been proven important in identifying patients at high risk of potential failure. The Transplant Evaluation Rating Scale (TERS) is a widely used rating instrument for the assessment of psychosocial risk factors before liver transplantation. The aim of this study was to explore the predictive value of TERS for mortality in liver transplant patients before and after transplantation. The medical records of patients referred for psychiatric evaluation before liver transplantation between 2003 -2013 were analysed. Administering TERS was part of the pre-transplant evaluation. The TERS scores of patients who died before and after transplantation were compared with those who survived following transplantation. One hundred and sixteen patients were referred for pre-transplant psychiatric evaluation. Patients with successful liver transplants scored significantly lower on TERS than those who died before transplantation (30.65 ± 6.06 vs. 34.75 ± 8.25, p = .031). Patients who died after transplantation scored significantly better on TERS than those who died before transplantation (28.79 ± 2.81 vs. 34.75 ± 8.25, p = .003). There was no significant difference between the deceased and surviving transplanted patients' TERS scores (28.79 ± 2.81 vs. 31.19 ± 6.66, p = .365). TERS appears to be a suitable rating instrument to help select candidates who have higher chance to survive prior to transplantation but it could not predict post-transplant mortality.

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.

Glycogen storage disease Ib is a rare, inherited metabolic disorder caused by glucose-6-phosphatase translocase deficiency. Its main symptoms are hypoglycemia, hyperlipidemia, neutropenia, hepatomegaly, liver adenomas and short stature. The exact mechanism of short stature in this disease is unclear, the most feasible possibility is that it is caused by impairment of growth-hormone and insulin-like growth factor I axis. Here we report the case of a patient who showed typical symptoms of glycogen storage disease Ib since his infancy, his height being under 1 percentile since then. Later-developed hypothyroidism and hypogonadism have also contributed to his short stature. Hypothyroidism was treated but sexual steroid substitution was not started because of an increased risk of hepatic adenomas. Because he developed hepatic adenoma at the age of 23, he had to undergo orthotopic liver transplantation. At the time of the transplantation his height was 128cm. The transplantation was followed by rapid height growth; our patient's height reached 160.3cm 62months after transplantation. We observed that while his IGF-I level increased, his GH level remained unchanged. During the post-transplantation period we ensured adequate calcium and vitamin D supplementation, leaving hormonal substitution unchanged. According to our knowledge, this is the first report of a rapid height growth as big as 32cm, of an individual over the age of 20, not related to endocrine treatment but liver transplantation.

Background. Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk of serious infectious complications. In 2009, a new influenza pandemic caused serious infections and deaths, especially among children and immunocompromised patients. Herein we have reported the safety and efficacy of a single-shot monovalent whole-virus vaccine against H1N1 infection in the pediatric renal transplant population. Methods. In November and December 2009, we vaccinated 37 renal transplant children and adolescents and measured their antibody responses. Seroprotection, seroconversion, and seroconversion factors were analyzed at 21 days after vaccination. Results. None of the vaccinated patients experienced vaccine-related side effects. None of the patients had an H1N1 influenza infection after vaccination. All of the patients showed elevations in antibody titer at 21 days after vaccination. In contrast, only 29.72% of the patients achieved a safe seroprotection level and only 18.75% a safe seroconversion rate. More intense immunosuppressive treatment displayed negative effect on seroprotection and seroconversion, and antibody production significantly increased with age. No other factor was observed to influence seroprotection. Conclusions. We recommend vaccination of children and adolescent renal transplant recipients against H1N1 virus. However, a single shot of vaccine may not be sufficient; to achieve seroprotection, a booster vaccination and measurement of the antibody response are needed to assure protection of our patients.

Introduction Recurrence of primary sclerosing cholangitis (rPSC) after liver transplantation (OLT) significantly affects longterm graft survival. We aimed to evaluate the incidence of rPSC and clinical data of these patients in Hungary. Patients and Methods We retrospectively analyzed data of 511 whole liver transplantations from 1995 to 2011. During the study period, 49 OLTs were performed in 43 adult patients with end-stage PSC (10%). Results Out of 49 OLT, 24 cases were excluded, rPSC was diagnosed in six patients (12%). Patients with rPSC had significantly higher mortality (p = 0.009) and graft loss (p = 0.009) in comparison to patients without recurrent disease. Younger recipient age, higher donor BMI was observed in the rPSC group. One patient was diagnosed with de novo IBD, the remaining five patients had worsening IBD activity in the posttransplant period. PreOLT colectomy was performed in 21% of the control and none of the rPSC group. PostOLT colectomy was performed in two rPSC patients due to severe therapy resistant colitis. Conclusions Recurrent PSC significantly affects long-term mortality and graft loss. Younger age at OLT, higher donor BMI and severe active IBD may be associated with PSC recurrence. PreOLT total colectomy might have protective effect against rPSC.

The history of organ transplantation in Hungary dates back to 50 years, and the first succesful liver transplantation was performed in the United States in that time as well. The number of patients with end stage liver disease increased worldwide, and over 7000 patients die in each year due to liver disease in Hungary. The most effective treatment of end-stage liver disease is liver transplantation. The indications of liver transplantation represent a wide spectrum including viral, alcoholic or other parenchymal liver cirrhosis, but cholestatic liver disease and acute fulminant cases are also present in the daily routine. In pediatric patients biliary atresia and different forms of metabolic liver disorders represent the main indication for liver transplantation. The results of liver transplantation in Hungary are optimal with over 80% long-term survival. For better survival individual drug therapy and monitoring are introduced in liver transplant candidates.Ötvenéves a magyar szervtranszplantáció, és ezzel egyidejűleg ötven évvel ezelőtt történt az első sikeres májátültetés az Egyesült Államokban, amelyet Thomas Starzl végzett. A világon évente több százezer, Magyarországon több mint 7000 ember hal meg májbetegségben. Az esetek nagy részében krónikus elégtelenségről van szó, de 10–15%-ban akut májelégtelenségről beszélhetünk, amelynek mortalitása műtét nélkül 80% feletti. A végstádiumú és akut májbetegek esetében a különféle konzervatív kezelési módszerek csak átmeneti megoldást jelentenek. Az egyetlen, hosszú távú túlélést jelentő gyógymód a transzplantáció. Napjainkban a májátültetést követő átlagos ötéves, úgynevezett kumulatív túlélés 80% feletti. Az indikációs terület egyre szélesebb, leggyakoribb a vírus és alkohol okozta cirrhosis és a cholestaticus májbetegségek miatt végzett májátültetés. Gyermekeknél főként fejlődési rendellenességek, congenitalis betegségek és metabolikus májbetegségek akut manifesztációi emelendők ki az indikációs körből. A májtranszplantációs túlélési eredményeink a jó nemzetközi statisztikáknak megfelelőek, de a graft- és betegtúlélés további javításában a testre szabott immunszuppressziós kezelés bevezetésének nagy jelentősége lehet. Orv. Hetil., 2013, 154, 858–862.

BackgroundLiver disease has become an important cause of morbidity and mortality even in those HIV-infected individuals who are devoid of hepatitis virus co-infection. The aim of this study was to evaluate the degree of hepatic fibrosis and the role of associated factors using liver stiffness measurement in HIV mono-infected patients without significant alcohol intake.MethodsWe performed a cross-sectional study of 101 HIV mono-infected patients recruited prospectively from March 1, 2014 to October 30, 2014 at the Center for HIV, St István and St László Hospital, Budapest, Hungary. To determine hepatic fibrosis, liver stiffness was measured with transient elastography. Demographic, immunologic and other clinical parameters were collected to establish a multivariate model. Bayesian Model Averaging (BMA) was performed to identify predictors of liver stiffness.ResultsLiver stiffness ranged from 3.0–34.3 kPa, with a median value of 5.1 kPa (IQR 1.7). BMA provided a very high support for age (Posterior Effect Probability-PEP: 84.5%), moderate for BMI (PEP: 49.3%), CD4/8 ratio (PEP: 44.2%) and lipodystrophy (PEP: 44.0%). For all remaining variables, the model rather provides evidence against their effect. These results overall suggest that age and BMI have a positive association with LS, while CD4/8 ratio and lipodystrophy are negatively associated.DiscussionOur findings shed light on the possible importance of ageing, overweight and HIV-induced immune dysregulation in the development of liver fibrosis in the HIV-infected population. Nonetheless, further controlled studies are warranted to clarify causal relations.

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

Background: Cytomegalovirus (CMV) presents a serious threat to CMV-seronegative recipients (R−), who have received an organ from a seropositive donor (D+). Objectives: We compared the effectiveness of three different prophylactic protocols in CMV D+/R− patients and reviewed data on patients who received no prophylaxis. Patients and methods: We reviewed 1137 kidney transplantations from 1995 to 2004. Of these, 147 recipients were CMV negative (D+/R−); 125 patients received CMV prophylaxis. Group I received CMV hyperimmune gammaglobulin only, group II received CMV hyperimmune gammaglobulin plus oral ganciclovir, and group III received prophylaxis with oral ganciclovir only. Results: In group I, CMV infection was observed in 31 of 53 patients (59%), and CMV disease was diagnosed in 9 (17%) during the prophylaxis. In the first year post transplant, a total of 41 of 53 patients (77.5%) had primary CMV infection. In group II, CMV infection occurred in 7 of 30 patients (23%), and CMV disease was diagnosed in only 2 (7%) during prophylaxis. In the first year post transplant, a total of 9 of 30 patients (30%) had primary CMV infection. In group III, 9 of 42 patients (21%) developed CMV infection during prophylaxis, and CMV disease was not observed. In the first year post transplant, a total of 13 of 42 patients (30%) had primary CMV infection. In contrast, all 22 CMV D+/R− patients without prophylaxis developed CMV infection (100%); CMV disease was diagnosed in 10 (45%), and 1 patient died. Conclusions: Prophylaxis with hyperimmune gammaglobulin and/or oral ganciclovir significantly reduces CMV infection and disease. Prophylaxis with ganciclovir was significantly more effective than hyperimmune gammaglobulin monoprophylaxis, and more cost effective than combined prophylaxis.

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

Recurrence of hepatitis C virus (HCV) after liver transplantation (OLT) occurs consistently. Early initiation of combined antiviral treatment (AVT) has become a standard treatment seeking to achieve sustained virological response (SVR). We evaluated the files of 108 HCV-positive patients between 2003 and 2010. Seventy-two (72) experienced recurrent HCV within 12 months, 31 of whom completed the AVT (43%) but 9 (29%) exhibited SVR. Factors with impacting SVR were male recipient, no fatty changes in the donor liver, short warm ischemia time, cyclosporine-based immunosuppression, neither infective, septic or bleeding complication nor acute rejection episode and a rapid viral response to AVT. De novo diabetes, and unsuccessful AVT prior to OLT were strongly associated with a a failed SVR. The 1- and 3-year cumulative patient survival rates trended to be better in cases of SVR compared with nonresponders (100% and 100% versus 94% and 89%; P = .07).

De novo diabetes mellitus is a common complication after liver transplantation. It is strongly associated with hepatitis C virus (HCV) infection. We analyzed the relationship between HCV recurrence and de novo diabetes among the Hungarian liver transplant population. This retrospective study included cases from 1995 to 2009 on 310 whole liver transplantations. De novo diabetes was defined if the patient had a fasting plasma glucose ≥126 mg/dL permanently after the third month post liver transplantation, and/or required sustained antidiabetic therapy. De novo diabetes occured in 63 patients (20%). The cumulative patient survival rates at 1, 3, 5, and 8 years were 95%, 91%, 88%, and 88% in the control group, and 87%, 79%, 79%, and 64% in the de novo group, respectively ( P = .011). The majority of the patients in the de novo group were HCV positive (66% vs 23%). Early virus recurrence within 5 months was associated with the development of diabetes (80% vs 20% non-diabetic controls; P = .017). The fibrosis (2.05 ± 1.5 vs 1 ± 1; P = .039) and Knodell scores (3.25 ± 2 vs 1.69 ± 1.2; P = .019) were higher among the de novo group after antiviral therapy. Rapid recurrence, more severe viremia, and fibrosis showed significant roles in the developement of de novo diabetes after liver transplantation.