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ZusammenfassungIn den letzten Jahren wurden bedeutsame Daten zur Biologie und Therapie des Riesenzelltumor des Knochens (RZTK) veröffentlicht. Ein entscheidender Durchbruch für die Diagnostik von RZTK war die Entdeckung der hoch tumorcharakteristischen Mutation im H3F3A-Gen, die zum Aminosäureaustausch G34W im Histon H3 führt. Zudem konnte sich in der Therapie die Behandlung von inoperablen RZTK mit dem anti-RANKL Antikörper Denosumab etablieren. Im Zusammenhang mit einer Denosumab-Therapie gibt es allerdings auch Berichte einer malignen Transformation des Tumors, wobei der konkrete Einfluss von Denosumab nicht eindeutig geklärt ist. Die Arbeitsgemeinschaft Knochentumoren (AGKT e. V.) hat daher eine multi-institutionelle Studie initiiert, um ein Kollektiv von RZTK zu etablieren mit dem Ziel a) morphologische Veränderungen unter Denosumab-Therapie detailliert zu beschreiben; b) Faktoren hinsichtlich einer potentiellen Malignisierung in ein Sarkom im Sinne einer Risikostratifizierung zu identifizieren; c) im direkten Vergleich RZTK im Rezidiv zu analysieren und mögliche Risikofaktoren hinsichtlich eines Rezidivs zu erarbeiten. Dafür wurden 26 RZTK vor und nach Denosumab-Therapie und 14 RZTK im Vergleich Primarius zu Rezidiv ohne Denosumab-Behandlung paarweise in die Studie eingeschlossen. Eingesetzte Techniken sind zunächst die histologische Beurteilung der morphologischen Veränderungen und die immunhistologische Analyse mittels eines breiten Panels an Markern. Das klinisch gut definierte Kollektiv soll im weiteren als Grundlage für eine Daten- und Gewebebank für zusätzliche molekularpathologische Analysen dienen.

Purpose: Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) has been found in a variety of malignant tumors and is associated with a poor prognosis. We aimed to explore the role of SPOCK1 in ovarian cancer. Methods: Ovarian cancer cell lines SKOV3 and SW626 were transfected with SPOCK1 overexpressing or empty vector using electroporation. Cells were studied by immunostaining and an automated Western blotting system. BrdU uptake and wound healing assays assessed cell proliferation and migration. SPOCK1 expression in human ovarian cancer tissues and in blood samples were studied by immunostaining and ELISA. Survival of patients with tumors exhibiting low and high SPOCK1 expression was analyzed using online tools. Results: Both transfected cell lines synthesized different SPOCK1 variants; SKOV3 cells also secreted the proteoglycan. SPOCK1 overexpression stimulated DNA synthesis and cell migration involving p21CIP1. Ovarian cancer patients had increased SPOCK1 serum levels compared to healthy controls. Tumor cells of tissues also displayed abundant SPOCK1. Moreover, SPOCK1 levels were higher in untreated ovarian cancer serum and tissue samples and lower in recipients of chemotherapy. According to in silico analyses, high SPOCK1 expression was correlated with shorter survival. Conclusion: Our findings suggest SPOCK1 may be a viable anti-tumor therapeutic target and could be used for monitoring ovarian cancer.

Monolayer cultures, the less standard three-dimensional (3D) culturing systems, and xenografts are the main tools used in current basic and drug development studies of cancer research. The aim of biofabrication is to design and construct a more representative in vivo 3D environment, replacing two-dimensional (2D) cell cultures. Here, we aim to provide a complex comparative analysis of 2D and 3D spheroid culturing, and 3D bioprinted and xenografted breast cancer models. We established a protocol to produce alginate-based hydrogel bioink for 3D bioprinting and the long-term culturing of tumour cells in vitro. Cell proliferation and tumourigenicity were assessed with various tests. Additionally, the results of rapamycin, doxycycline and doxorubicin monotreatments and combinations were also compared. The sensitivity and protein expression profile of 3D bioprinted tissue-mimetic scaffolds showed the highest similarity to the less drug-sensitive xenograft models. Several metabolic protein expressions were examined, and the in situ tissue heterogeneity representing the characteristics of human breast cancers was also verified in 3D bioprinted and cultured tissue-mimetic structures. Our results provide additional steps in the direction of representing in vivo 3D situations in in vitro studies. Future use of these models could help to reduce the number of animal experiments and increase the success rate of clinical phase trials.

The 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. The indication of therapy in patients with no contraindication is based on the 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. Interferon-based or interferon-free therapies are available for the treatment. Due to their limited success rate as well as to their (sometimes severe) side-effects, the mandatory use of interferon-based therapies as first line treatment can not be accepted from the professional point of view. However, they can be used as optional therapy in treatment-naïve patients with mild disease. As of interferon-free therapies, 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 of Hungary and patients’ organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv Hetil. 2018; 159(Suppl 1): 3–23.

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.

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.

A multidrug-resistant Pseudomonas aeruginosa PS1 isolated from urine clinical sample was investigated in this study. The strain exhibited resistance to piperacillin/tazobactam, ciprofloxacin, imipenem, ceftazidime but it was susceptible to colistin. Analysis of whole-genome sequencing data by ResFinder detected various resistance determinants including qnrVC1 and blaNDM-1. The multiresistant P. aeruginosa isolate belonged to ST773 high-risk clone. The qnrVC1 and blaNDM-1 determinants were incorporated into different integrons. Expression of blaNDM-1 was fourfold and qnrVC1 was twofold increased, compared to that of rpsL housekeeping gene. Mutations in gyrA Thr83Leu and parC Ser87Leu were detected and additionally qnrVC1 expression indicates protective effect of QnrVC1 pentapeptid protein on gyrase and topoisomerase. High-risk P. aeruginosa clones integrate various carbapenemase and other resistance determinants into their genomes that facilitates further dissemination of multiresistance among clinical isolates. We report blaNDM-1 and qnrVC1 genes in P. aeruginosa ST773 international high-risk clone.

New therapeutic options became available in 2015 in the European Union. We present the availability of interferon-free regimens with direct acting antivirals (DAA) in four Central European countries – the Czech Republic, Hungary, Poland and Slovakia – which despite similar historical, geographical and economic situations demonstrate different systems for access to anti-HCV (hepatitis C virus) medication. Treatment of patients in the Czech Republic was based in 2015 on an exceptional individual reimbursement procedure, but regular reimbursement procedures are expected in 2016. In Hungary the decision for treatment is balanced against budget limitations and the national Priority Index system reflecting stage of liver disease, activity of the disease and predictive factors. A reimbursed interferon (IFN)-free therapeutic program for all genotypes, without restrictions related to hepatic fibrosis and treatment history, is already available in Poland. In Slovakia patients with advanced fibrosis are currently selected for possible IFN-free therapy in 2016.

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 2016 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 ente- cavir 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. 2) 25–36.

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.

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. From a socioeconomic aspect, this could also prevent further spread of the virus as well as reduce substantially long term financial burden of related morbidity. 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 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 (elastography and biochemical methods) are accepted and preferred for staging liver damage (fibrosis). For initiation of treatment as well as for on-treatment decisions, 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(Suppl. 1), 3–23.

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.

The 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. The indication of therapy in patients with no contraindication is based on the 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. Interferon-based or interferon-free therapies are available for the treatment. Due to their limited success rate as well as to their (sometimes severe) side-effects, the mandatory use of interferon-based therapies as first line treatment can not be accepted from the professional point of view. However, they can be used as optional therapy in treatment-naïve patients with mild disease. As of interferon-free therapies, 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 of Hungary and patients' organizations. Interferon-free treatments and shorter therapy durations are preferred. Orv Hetil. 2018; 159(Suppl 1): 3-23.

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.

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.

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Background It remains unclear if the vascular and connective tissue structures of primary and metastatic tumors are intrinsically determined or whether these characteristics are defined by the host tissue. Therefore we examined the microanatomical steps of vasculature and connective tissue development of C38 colon carcinoma in different tissues. Methods Tumors produced in mice at five different locations (the cecal wall, skin, liver, lung, and brain) were analyzed using fluorescent immunohistochemistry, electron microscopy and quantitative real-time polymerase chain reaction. Results We found that in the cecal wall, skin, liver, and lung, resident fibroblasts differentiate into collagenous matrix-producing myofibroblasts at the tumor periphery. These activated fibroblasts together with the produced matrix were incorporated by the tumor. The connective tissue development culminated in the appearance of intratumoral tissue columns (centrally located single microvessels embedded in connective tissue and smooth muscle actin-expressing myofibroblasts surrounded by basement membrane). Conversely, in the brain (which lacks fibroblasts), C38 metastases only induced the development of vascularized desmoplastic tissue columns when the growing tumor reached the fibroblast-containing meninges. Conclusions Our data suggest that the desmoplastic host tissue response is induced by tumor-derived fibrogenic molecules acting on host tissue fibroblasts. We concluded that not only the host tissue characteristics but also the tumor-derived fibrogenic signals determine the vascular and connective tissue structure of tumors.

Ten years have elapsed since the severe acute respiratory syndrome outbreak, which resulted in more than 8000 cases worldwide with more than 700 deaths. Recently, a new coronavirus, the Middle East Respiratory Syndrome Coronavirus emerged, causing serious respiratory cases and death. By the end of August 2013, 108 cases including 50 deaths were reported. The authors discuss a coronavirus-associated severe acute respiratory syndrome, which was detected in Hungary in 2005 and highlight its significance in 2013. In 2005 the patient was hospitalized and all relevant clinical and microbiological tests were performed. Based on the IgG antibody positivity of the serum samples, the patient was diagnosed as having severe acute respiratory syndrome coronavirus infection in the past. The time and source of the infection remained unknown. The condition of the patient improved and he was discharged from the hospital. The case raises the possibility of infections in Hungary imported from remote areas of the world and the importance of thorough examination of patients with severe respiratory syndrome with unknown etiology.Tíz évvel ezelőtt a súlyos akut respirációs szindrómát okozó coronavírus által okozott járvány több mint 8000 embert betegített meg, és több mint 700 halálesetet okozott. Jelenleg egy új coronavírus, a Middle East Respiratory Syndrome Coronavirus okoz megbetegedéseket és haláleseteket; 2013. augusztus végéig 108 megbetegedést jelentettek, amelyből 50 halállal végződött. A szerzők beszámolnak egy 2005-ben Magyarországon észlelt súlyos akut respirációs szindrómát okozó coronavírus-fertőzésről, és utalnak annak jelentőségére 2013-ban. A 2005-ben kórházba felvett beteg teljes klinikai és mikrobiológiai kivizsgáláson esett át. A beteg vérsavójában súlyos akut respirációs szindrómát okozó coronavírus-specifikus IgG ellenanyagokat mutattak ki. A fertőzés időpontja és forrása nem volt ismert, felismerése a savó széles körű szerológiai vizsgálatán alapult. Esetük felhívja a figyelmet arra, hogy a távoli országokból behurcolt fertőző betegségek Magyarországon is felbukkanhatnak. Lényeges minden olyan súlyos légúti betegség alapos kivizsgálása, amelynek oka nem tisztázott. Jelenleg különösen fontos ez olyan betegek esetében, akik előzőleg a Közel-Kelet vagy Távol-Kelet országaiban jártak. Orv. Hetil., 2013, 154(47), 1877–1882.

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.

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.