[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 22 September 2017]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2017. szeptember 22-tol.

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.

[Screening, diagnosis, treatment, and follow up of hepatitis C virus related liver disease. National consensus guideline in Hungary from 15 October 2016]. / A hepatitis C-vírus-fertozés szurése, diagnosztikája, antivirális terápiája, kezelés utáni gondozása. Magyar konszenzusajánlás. Érvényes: 2016. október 15-tol.

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.

Hepatitis C-vírus-fertozés: diagnosztika, antivirális terápia, kezelés utáni gondozás. Magyar konszenzusajánlás. Érvényes: 2015. szeptember 12-tol.

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.

[Changing times - changing diseases. Review of the neuropathological autopsy documentations at the Markusovszky University Teaching Hospital (1964-2014)]. / Változó idok - változó betegségek. A Markusovszky Egyetemi Oktatókórház neuropatológiai autopsziás anyagának áttekintése (1964-2014).

INTRODUCTION: Nearly 6000 autoptic studies were carried out during the last 50 years at the Laboratory of Neuropathology, Markusovszky University Teaching Hospital, Hungary. AIM: The aim of the authors was to present those previously frequent and often fatal conditions that can be prevented or treated today. METHOD: Retrospective analyses of the neuropathological documentations. RESULTS: Measles-related subacute sclerosing panencephalitis caused death in 13 cases, the last occurred in 1991. The mandatory vaccination against the causative virus has eliminated this severe neurological complication. Fourteen lives were lost due to herpes simplex encephalitis, including the last case seen in 1999. Feasibility of early diagnosis and the availability of acyclovir therapy resulted in better outcome without fatality. Tuberculous meningitis still occurred in most recent years, although only sporadically. Recognition of this condition is not straightforward due to its rarity, and considerations for this disease are often omitted from the routine differential diagnosis. The generally low mortality rates in tick borne encephalitis further dropped after the introduction of vaccination. Altogether only 8 such cases were documented. The last fatal cases of neurolues were seen in the 1990s. However, syphilis itself has not disappeared, and the number of cases with newly acquired infection continues to rise. The introduction of intrathecal methotrexate and radiotherapy made possible the prevention or effective treatment of meningeal leukosis. A careful coordination of these treatment modalities, however, is important as nervous system complications may develop in the form of disseminated necrotizing leukoencephalopathy that is also reflected in the records. CONCLUSIONS: The 50-year neuropathology documentation reflects changes in the occurrence of diseases, and it calls attention to those disorders which can be prevented or treated today, but may represent diagnostic challenges.

[Changing prevalence of Helicobacter pylori infection in the 9th district of Budapest. A retrospective endoscopic study, 1997-2012]. / A Helicobacter pylori-fertozés epidemiológiája Ferencvárosban. Retrospektív endoszkópos tanulmány, 1997-2012.

BACKGROUND: The prevalence of Helicobacter pylori infection in developed countries is decreasing. The time-frame of this process is largely unknown. AIM: The aim of the authors was to evaluate the changes in the prevalence of Helicobacter pylori infection in their endoscopic centre. METHODS: This retrospective study included 4647 patients examined between 1997 and 2012. Helicobacter pylori was determined from antral and corpus biopsies by the modified Giemsa stain and rapid urease test. The prevalence of the infection was calculated yearly for the period studied, for age decades from 18 to 85 years, birth cohorts of 10 years from 1920 to 1994 and according to diagnosis. RESULTS: The overall prevalence of Helicobacter pylori infection was 54.7%, which decreased from 71.3% in 1997 to 32.76% in 2011. Functional dyspepsia was found in 37.9%, duodenal ulcer in 25.3%, gastric ulcer in 3.8% and reflux disease in 24.2% of the patients. The mean prevalence of infection was 62.5% in birth cohorts of 10 years between 1920 and 1959, 57.4% in those between 1960 and 1969, and decreased to 39.0% and 26.7% in birth cohorts between 1970 and 1979) and between 1980 and 1989, respectively. According to age cohorts, the prevalence was 21.8% 34.9%, 46.5%, 63.7%, 63.2% and 59.2% in patients aged 18-19 years, 20-29 years, 30-39 years, 40-49 years, 50-59 years and 60-69 years, respectively. The proportion of H. pylori positive duodenal ulcers decreased from 95.9% in 1998 to 59.1% in 2011 (p = 0.001). CONCLUSIONS: The prevalence of Helicobacter pylori infection in the 9th district of Budapest is decreasing, especially in cohorts born in the late 1960s and 1970s, nearly 1.5 decades before the discovery of the bacterium.

[Quality assurance of rapid on-site evaluation of CT-guided fine-needle aspiration cytology of lung nodules]. / A CT-vezérelt vékonytu-aspirációs citológiai vizsgálat minoségbiztosítása a tüdodaganatok diagnosztikájában.

INTRODUCTION: The methods available for the diagnosis of lung cancer include radiologic, cytologic and pathologic procedures. AIMS: The aim of this study was to determine the quality assurance of CT guided fine needle aspiration cytology of lung nodules. METHODS: Cytology results were rated to 4 categories (positive; suspicious; negative; not representative). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 128 patients underwent CT-guided percutaneous fine-needle aspiration biopsy cytology (63 males; 65 females; mean age 62.8 years). Smears were adequate in 99 cases and inadequate in 29 cases. The average diameter of the nodules was 3.28 cm. Thirty three (25.6%) of the cases were histologically verified and 2 falsely negative and 2 falsely positive cases were detected. The sensitivity and the positive predictive value were 88.8% and 88.8%, respectively. Pneumothorax developed in 7 (5.4%) cases. CONCLUSION: These results suggest that CT-guided transthoracic fine needle aspiration cytology has a high diagnostic accuracy and an acceptable complication rate. The auditing valves of the results meet the proposed threshold values.

Hepatitis C Screening and Treatment Program in Hungarian Prisons in the Era of Direct Acting Antiviral Agents.

A hepatitis C virus (HCV) screening and treatment program was conducted in Hungarian prisons on a voluntary basis. After HCV-RNA testing and genotyping for anti-HCV positives, treatments with direct-acting antiviral agents were commenced by hepatologists who visited the institutions monthly. Patients were supervised by the prisons' medical staff. Data were retrospectively collected from the Hungarian Hepatitis Treatment Registry, from the Health Registry of Prisons, and from participating hepatologists. Eighty-four percent of Hungarian prisons participated, meaning a total of 5779 individuals (28% of the inmate population) underwent screening. HCV-RNA positivity was confirmed in 317/5779 cases (5.49%); 261/317 (82.3%) started treatment. Ninety-nine percent of them admitted previous intravenous drug use. So far, 220 patients received full treatment and 41 patients are still on treatment. Based on the available end of treatment (EOT) + 24 weeks timepoint data, per protocol sustained virologic response rate was 96.8%. In conclusion, the Hungarian prison screening and treatment program, with the active participation of hepatologists and the prisons' medical staff, is a well-functioning model. Through the Hungarian experience, we emphasize that the "test-and-treat" principle is feasible and effective at micro-eliminating HCV in prisons, where infection rate, as well as history of intravenous drug usage, are high.

Screening and treatment of hepatitis C virus in prisons: 10 years of experience / A hepatitis C-vírus szurésének és kezelésének 10 éves tapasztalata a börtönökben

Introduction and objective: Two-thirds of patients with hepatitis C virus (HCV) infection are unaware of their infection in the European Union. The WHO aims to reduce the number of new cases of chronic hepatitis by 90% by 2030. The proportion of people infected with HCV in prisons can be up to ten times higher compared to the general population. This article is a summary of the results of the HCV screening carried out in the Hungarian prisons between 2007 and 2017. Method: Screening of anti-HCV antibodies has been performed on a voluntary basis followed by HCV PCR and genotyping in positive cases. After obtaining written informed consent from the patients, treatment was started. Treatments were performed under the guidance of hepatologists in collaboration with prison medical staff. Results: HCV screening programs and treatments are in place in 84% of Hungarian prisons. A total of 25 384 patients underwent anti-HCV screening. Anti-HCV positive result was detected in 6.6% and HCV PCR positivity was confirmed in 3.8% of the screened inmates. 55.2% patients from the HCV PCR positive population were put on treatment. Only 143 patients received full treatment, while 162 (42.6%) treatments were terminated prematurely, and the duration of treatment was unknown in 75 patients. Based on the results available on the 24th week after the end of treatment, sustained virologic response rate was 88%. Discussion: Education of patients and collaboration between hepatologists and prison medical staff play an important role in the successful result of treatment. Conclusion: Our experience demonstrates that the test and treat principle is feasible and effective at microeliminating HCV in prisons.

[The "gray zone" in organized mammography screening: histocytological correlations]. / A "szürke zóna" az emlorák mammográfiás szervezett szurésében. Citológiai-hisztológiai tanulmány.

UNLABELLED: The National Public Health Program has established the organized mammography screening in Hungary. The aim of this study was to conduct an audit of "gray zone" smears of the organized mammography screening in comparison with histopathological diagnoses. METHODS: Cytology results were rated to C3 atypia probably benign and C4 suspicious of malignancy. RESULTS: 1361 women had aspiration cytology performed from a total of 47,718 mammography non-negative lesions. 105 (7.8%) were diagnosed as C3, whereas 78 (5.7) as C4. Of the 105 patients with C3 diagnosis 61 (58%) patients underwent surgical biopsy. Histology proved malignancy in 20 (32.8%) cases, and benign lesion in 41 (67.2%) cases. All (100%) of the 78 patients with C4 diagnosis had open biopsies; 69 (88.4%) cases were histologically malignant and 9 (11.6%) cases were benign lesions. CONCLUSION: The auditing results of fine needle aspiration cytology of "gray zone" in organized mammography screening meet the proposed threshold values. Authors conclude that the "gray zone" category in breast cytology is useful and of value if used judiciously.

[Quality assurance of fine-needle aspiration cytology of the organized mammography screening]. / Az emlo mammográfiás szervezett szurésének citológiai minoségbiztosítása.

UNLABELLED: The National Public Health Program has established the organized mammography screening in Hungary. AIM: The aim of our study was to determine the quality assurance of breast aspiration cytology. METHOD: Cytology results were rated to 5 categories (C1, C2, C3, C4 and C5). All cytology reports were compared with the final histology diagnosis. RESULTS: 1361 women had aspiration cytology diagnosis performed from a total of 47718 mammography non-negative lesions. There were 805 (59.1%) benign and 187 (13.7%) malignant alterations. Sensitivity was 91%, specificity 88%, positive predictive value 96.6% and negative predictive value turned to be 71% (p<0.001). CONCLUSION: The auditing values of fine needle aspiration cytology in our laboratory meet, or in certain aspects exceed the proposed minimum threshold values.

[Whooping cough in an urban high school in Hungary. Conclusions of a local pertussis outbreak]. / Pertussis egy szombathelyi középiskolában. Egy járvány tanulságai.

UNLABELLED: Although incidence of pertussis has been gradually decreased with the introduction of active immunization, total eradication is not possible. This has been shown by national and international data, as well. In the early 2000's, slow increase in incidence of pertussis was observed. AIM: To demonstrate the presence of Bordetella pertussis in the Hungarian population by presenting 17 cases of adolescent pertussis. METHODS: Etiology of pertussis was confirmed by quantification of pertussis-antibodies in blood samples taken from permanently coughing patients in the firstly identified subject's vicinity which latter was explored by retrospective data collection. RESULTS: In the vicinity of the first identified patient epidemiologic research identified another 16 patients all of which were confirmed by serological tests. CONCLUSIONS: If permanent coughing is present, pertussis needs to be ruled out. Immunity against pertussis obtained by vaccination fades by the end of childhood. Bordetella pertussis circulates in the national population. A booster-vaccination against pertussis in the regular vaccination course for the 11-year old children is recommended. Pertussis in adolescents and in adults is mild and atypical, but in case of prolonged coughing it needs to be considered.

[Post vaccination rotavirus surveillance in Hungary, in 2007]. / Posztvakcinációs rotavírus-surveillance Magyarországon, 2007.

Vaccination is the main strategy to control severe dehydrating gastroenteritis caused by rotaviruses in early childhood. The availability of new generation rotavirus vaccines has led to an intensification of strain surveillance worldwide, in part, to gauge the impact of the possible vaccine-driven immune selection of wild-type rotavirus strains. In the present study, authors describe the strain prevalence data obtained in 2007, with the involvement of different regions of Hungary. Genomic RNA was extracted from rotavirus-positive stool samples collected mainly from children and then subjected to genotyping using multiplex RT-PCR assay. Type-specific primers targeted G1 to G4, G6, G8 to G10, and G12 VP7 specificities, and P[4], P[6], and P[8] to P[11] VP4 specificities were used. Out of 489 rotavirus-positive specimens, collected from 482 patients, 466 and 474 were successfully G and P typed, respectively, and both G and P type specificities could be assigned for 457 strains. Prevalence data showed the predominance of G4P[8] (31.5%) strains, followed by G1P[8] (28.3%), G2P[4] (19.3%), and G9P[8] (10.2%). Minority strains were G1P[4] (0.4%), G2P[8] (1.3%), G3P[9] (0.2%), G4P[6] (0.7%), G6P[9] (0.4%), G8P[8] (0.2%), G9P[4] (0.2%), G9P[6] (0.8%), and G12P[8] (0.4%). Mixed infections were found in 1.2% of the samples, while 4.9% remained partially or fully non-typified. Our data indicate that the antigen specificities of medically important rotavirus strains identified in this 1-year study are well represented in the vaccines available in the pharmaceutical private market in Hungary. Depending on the vaccination coverage achievable in the forthcoming years, the post-vaccination rotavirus strain surveillance may allow us to gain comprehensive information on the impact of rotavirus vaccines on the prevalence of circulating rotavirus strains.

[Evaluation of the epidemiological and clinical characteristics of central nervous system infections in adults in the West Pannonian region]. / A felnottkori neuroinfekciók epidemiológiai és klinikai jellemzoinek vizsgálata a nyugat-dunántúli régióban.

Introduction: Despite advancements in diagnostic capabilities and the availability of effective antimicrobial agents, community-acquired infections of the central nervous system (CNS) are still associated with high mortality rates. Aim: To assess the epidemiological and clinical characteristics of community-acquired CNS infections treated in the West Pannonian region between 2010 and 2016. Method: Clinical data of 176 patients were retrospectively analysed in two age cohorts: 15 to 65 and more than 65 years of age. Results: Neuroinfections were found to be bacterial in 81, viral in 91, parasitic in 1 and mixed in 3 cases during the observation period. The most frequent bacterial pathogens isolated were Streptococcus pneumoniae (20%) and Borrelia burgdorferi (16%). The most frequent viral pathogens isolated were tick-borne encephalitis virus (37%), herpes simplex virus (10%) and enterovirus (7%). Aetiology was unknown in 40 percent of all cases. The average incidence rate was 9.8/100 000 person/year with a mortality rate of 12%. In the cohort of patients aged >65 years, significantly higher frequencies of immunocompromising factors, lower Glasgow Coma Scale values at admission and confusion were observed (p-values: 0.008, 0.017, and 0.050, respectively). Prognosis was negatively influenced by low Glasgow Coma Scale values at admission (OR = 1.6 CI95%: 1.3-1.9; p<0.001), old age (OR = 6.5 CI95%: 2.5-17.1; p<0.001) and immunodeficiency (OR = 3.1 CI95%: 1.2-8.1; p = 0.019). Conclusions: S. pneumoniae remains the most frequently observed causative bacterial pathogen associated with community-acquired CNS infections. Incidence of tick-borne encephalitis in our county is higher than the national average (2.3 versus 0.35/100 000 person/year). Orv Hetil. 2019; 160(40): 1574-1583.

Ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin in HCV genotype 1 infected patients who failed previous protease inhibitor therapy.

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.

[EuroRotaNet--European rotavirus strain surveillance network established with Hungarian participation]. / Hazai részvétellel megalakult az Európai Rotavírus-törzs-figyelô Hálózat (EuroRotaNet).

Group A rotaviruses are the most common cause of severe gastroenteritis worldwide. The incidence and distribution of group A rotavirus sero/genotypes varies between geographical areas during a rotavirus season, and from one season to the next. In addition, cocirculation of genetically diverse multitypic rotaviruses and of intratypic variants in any one place and time is common. Assuming widespread use of rotavirus vaccine in the near future, comprehensive surveillance of natural rotavirus infections is vital. EuroRotaNet has been established in order to gather comprehensive information on the rotavirus types co-circulating throughout Europe. The main objectives of the network are to (i) develop methods and algorithms for effective rotavirus strain typing and characterisation, (ii) describe in detail the molecular epidemiology of rotavirus infections in Europe, (iii) monitor the effectiveness of current genotyping methods and respond to changes associated with genetic drift and shift, and (iv) monitor the emergence and spread of novel rotavirus strains within Europe. This infrastructure may serve as a platform for future surveillance activities and nested studies for evaluating the effectiveness of a rotavirus vaccine in the general population. Studies to monitor the reduction in disease associated with common rotavirus types, the possible vaccine-induced emergence of antibody escape mutants of genotypes other than those included in the vaccine and of reassortment between vaccine and naturally circulating wildtype strains are required.

[Atypical glandular cells (AGC) on Papanicolaou smears--the great challenge of cervix screening programs]. / Kóros mirigyhámsejtek cervixkenetekben--a méhnyakszurés nagy kihívása.

UNLABELLED: The "grey zone" diagnostic category for glandular cells in the Bethesda System 2001 (TBS 2001) has undergone significant modification since its last version in 1991. PATIENTS: The aim of the study was to follow up patients with "atypical glandular cells of undetermined significance" (AGUS)/ "atypical glandular cells" (AGC), and adenocarcinoma cytological interpretation, based on a three-year material between 2000-2002 at the Department of Cytopathology of National Institute of Oncology, Hungary. The smears were reviewed and interpreted according to TBS 2001. Histological slides were reviewed and cytohistologic correlations were investigated. RESULTS: Out of 36193 conventional Papanicolaou smears, there were 276 AGC-NOS (AGUS, favour reactive in TBS1991) and 7 AGC-favour neoplastic (AGUS, favour neoplastic in TBS 1991) (altogether 0.78%) and 35 (0.1%) adenocarcinoma interpretations. Histology was available in 136 (AGC-NOS: 106, AGC-favour neoplastic: 7 and adenocarcinoma: 23) cases. Among the followed 106 patients with AGC-NOS, there were 24 cases with concurrent "grey zone" squamous, ASC-US, interpretation. Clinically significant lesions were found in 5/7 (71%) of cases of the AGC-favour neoplastic group, and in 27/106 (25%) of the all AGC-NOS group, the difference is statistically significant. This ratio is 16/82 (20%) in the AGC-NOS only cases, while 11/24 (46%), in the AGC-NOS with concurrent ASC-US cases, the difference is statistically significant. The high-grade lesions were mostly squamous. CONCLUSION: The results suggest that AGC-NOS with concurrent ASC-US interpretation represent a group of potential patients with statistically significant higher risk of clinically significant (among them high-grade) lesions.

Large-scale whole genome sequencing identifies country-wide spread of an emerging G9P[8] rotavirus strain in Hungary, 2012.

With the availability of rotavirus vaccines routine strain surveillance has been launched or continued in many countries worldwide. In this study relevant information is provided from Hungary in order to extend knowledge about circulating rotavirus strains. Direct sequencing of the RT-PCR products obtained by VP7 and VP4 genes specific primer sets was utilized as routine laboratory method. In addition we explored the advantage of random primed RT-PCR and semiconductor sequencing of the whole genome of selected strains. During the study year, 2012, we identified an increase in the prevalence of G9P[8] strains across the country. This genotype combination predominated in seven out of nine study sites (detection rates, 45-83%). In addition to G9P[8]s, epidemiologically major strains included genotypes G1P[8] (34.2%), G2P[4] (13.5%), and G4P[8] (7.4%), whereas unusual and rare strains were G3P[8] (1%), G2P[8] (0.5%), G1P[4] (0.2%), G3P[4] (0.2%), and G3P[9] (0.2%). Whole genome analysis of 125 Hungarian human rotaviruses identified nine major genotype constellations and uncovered both intra- and intergenogroup reassortment events in circulating strains. Intergenogroup reassortment resulted in several unusual genotype constellations, including mono-reassortant G1P[8] and G9P[8] strains whose genotype 1 (Wa-like) backbone gene constellations contained DS1-like NSP2 and VP3 genes, respectively, as well as, a putative bovine-feline G3P[9] reassortant strain. The conserved genomic constellations of epidemiologically major genotypes suggested the clonal spread of the re-emerging G9P[8] genotype and several co-circulating strains (e.g., G1P[8] and G2P[4]) in many study sites during 2012. Of interest, medically important G2P[4] strains carried bovine-like VP1 and VP6 genes in their genotype constellation. No evidence for vaccine associated selection, or, interaction between wild-type and vaccine strains was obtained. In conclusion, this study reports the reemergence of G9P[8] strains across the country and indicates the robustness of whole genome sequencing in routine rotavirus strain surveillance.

Surveillance of human rotaviruses in 2007-2011, Hungary: exploring the genetic relatedness between vaccine and field strains.

BACKGROUND: The availability of rotavirus vaccines has resulted in an intensification of post vaccine strain surveillance efforts worldwide to gain information on the impact of vaccines on prevalence of circulating rotavirus strains. OBJECTIVES: In this study, the distribution of human rotavirus G and P types in Hungary is reported. In addition, the VP4 and VP7 genes of G1P[8] strains were sequenced to monitor if vaccine-derived strains were introduced and/or some strains/lineages were selected against. STUDY DESIGN: The study was conducted in 8 geographic areas of Hungary between 2007 and 2011. Rotavirus positive stool samples were collected from diarrheic patients mostly <5 years of age. Viral RNA was amplified by multiplex genotyping RT-PCR assay, targeting the medically most important G and P types. When needed, sequencing of the VP7 and VP4 genes was performed. RESULTS: In total, 2380 strains were genotyped. During the 5-year surveillance we observed the dominating prevalence of genotype G1P[8] (44.87%) strains, followed by G4P[8] (23.4%), G2P[4] (14.75%) and G9P[8] (6.81%) genotypes. Uncommon strains were identified in a low percentage of samples (4.12%). Phylogenetic analysis of 318 G1P[8] strains identified 55 strains similar to the Rotarix strain (nt sequence identities; VP7, up to 97.9%; VP4, up to 98.5%) although their vaccine origin was unlikely. CONCLUSIONS: Current vaccines would have protected against the majority of identified rotavirus genotypes. A better understanding of the potential long-term effect of vaccine use on epidemiology and evolutionary dynamics of co-circulating wild type strains requires continuous strain surveillance.

First detection of P[6],G9 rotaviruses in Hungary--an imported strain from India?

EuroRotaNet was launched to monitor rotavirus strain prevalence during and after introduction of rotavirus vaccines in Europe. In early 2007, we detected P[6],G9 rotaviruses to appear in Hungary, representing the first documented occurrence of this strain in our surveillance area. Epidemiologic data suggested that this strain was introduced from India.