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.

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.

Identifying risks for severity of neurological symptoms in Hungarian West Nile virus patients.

BACKGROUND: West Nile virus (WNV) infections have become increasingly prevalent in certain European countries, including Hungary. Although most human infections do not cause severe symptoms, in approximately 1% of cases WNV infections can lead to severe WNV neuroinvasive disease (WNND) and death. The goal of our study was to assess the neurological status changes of WNV -infected patients admitted to inpatient care and to identify potential risk factors as underlying reasons for severe neurological outcome. METHODS: We conducted a retrospective chart review of 66 WNV-infected patients from four Hungarian medical centers. Patients' neurological status at hospital admission and at two follow-up intervals (1st follow-up, within 60-90 days and 2nd follow-up, within 150-180 days, after hospital discharge) were assessed. All of the 66 patients in the initial sample had some type of neurological symptoms and 56 patients were diagnosed with WNND. The modified Rankin Scale (mRS) and the West Nile Virus Neurological Index (WNV-N Index), a scoring system designed for the purpose of this study, were used for neurological status assessment. Patients were dichotomized into two categories, "moderately severe" and "severe" based on their neurological status. Descriptive analysis for sample description, stratified analysis for calculation of odds ratio (OR) and logistic regression for continuous input variables, were performed. RESULTS: The average number of days between the onset of neurological symptoms and hospital admission (the neurological symptom interval) was 6.01 days. Complications during the hospital stay arose in almost a fifth of the patients (18.2%) and 5 patients died. Each day's increase in the neurological symptom interval significantly increased the risk for developing a severe neurological status following hospital admission (0.799-fold and 0.688-fold, based on the WNV-N Index and mRS, respectively). Patients' age, comorbidity, presence of complications and symptoms of malaise, and gait uncertainty were shown to be independent risk factors for severe neurological status. CONCLUSIONS: Timely hospital admission of patients with neurological symptoms as well as risk assessment by clinicians - possibly with an optimal assessment tool for estimating neurological status- could improve the neurological outcome of WNV-infected patients.

[Detection of West Nile virus in human samples: follow-up studies during the 2015 seasonal period]. / A nyugat-nílusi vírus kimutatása humán betegmintákból: nyomon követéses vizsgálatok a 2015. évi szezonális idoszakban.

INTRODUCTION: West Nile virus, a mosquito-borne viral zoonosis is responsible for human infections in Hungary. Laboratory diagnosis is based on serological tests, however the application of molecular methods has been appreciated. AIM: The aim of the study was to investigate blood, cerebrospinal-fluid and urine samples of acutely ill patients and to follow-up PCR positive cases to ascertain the length of virus excretion. METHOD: Clinical specimens were examined by indirect-immunofluorescent, haemagglutination-inhibition, two PCR tests and Sanger-sequencing. Virus isolation in case of two patients was successful. RESULTS: A follow-up study could be carried out in case of 5 patients. Viral nucleic acid was detectable in urine even for several weeks after symptom onset and viral RNA was present at higher concentration compared with other samples. CONCLUSIONS: PCR analysis of urine could provide useful epidemiological and diagnostic information. Therefore, it is recommended to collect urine samples in order to supplement the serological diagnosis. Orv Hetil. 2017; 158(20): 791-796.

[Efficacy and safety of boceprevir based triple therapy in Hungarian patients with hepatitis C genotype 1 infection, advanced stage fibrosis and prior treatment failure]. / Bocepreviralapú hármas kezelés hatékonyságának és biztonságosságának retrospektív elemzése elorehaladott fibrosisstádiumú, hepatitis C-vírus 1-es genotípussal fertozött, korábban sikertelenül kezelt magyar betegeknél.

INTRODUCTION: During 2011 and 2013, 155 Hungarian hepatitis C genotype 1 infected patients, mostly with advanced liver fibrosis, who did not respond to prior peginterferon + ribavirin dual therapy, started boceprevir based triple therapy in an early access program. AIM AND METHOD: Efficacy and safety of the therapy was retrospectively assessed based on sustained virologic responses, as well as on frequency and type of serious adverse events and of those leading to therapy discontinuation. RESULTS: In an intent-to-treat analysis 39.4% patients (61/155) reached sustained virologic response. Amongst pervious relapsers, partial responders and null-responders 59.5%, 41.4 % and 22.9% (p<0.05 compared to the other two categories) reached sustained virologic response, respectively, while amongst non-cirrhotics and cirrhotics 52.5% and 31.3% (p<0.05 compared to the non-cirrhotics) achieved sutained virologic response, respectively. Six out of the 33 most difficult to cure patients (previous null responder and cirrhotic) have reached sustained virologic response (18.2%). Frequency of early discontinuations due to insufficient virologic response was 31.1%, while due to adverse event 10.3%. Reported frequency of serious adverse event was 9.8%. These events represented anemia, diarrhoea, depression, agranulocytosis, elevated aminotransferases, generalized dermatitis and severe gingivitis with loss of teeth, prolonged QT interval on ECG, generalized oedema and severe dyspnoea, uroinfection, exacerbation of Crohn's disease, Campylobacter pylori infection and unacceptable weakness and fatigue. Eight patients received transfusion, 4 patients erythropoietin and 1 granulocyte colony stimulating factor during therapy. No death has been reported. CONCLUSIONS: With boceprevir based triple therapy, one of the bests available in 2011-2013 in Hungary, a relevant proportion of hepatitis C infected patients with advanced liver fibrosis achieved sustained viral response. In this cohort, side-effects resembled those reported in registration studies, and resulted in therapy discontinuation with consequent treatment failure in a relevant number of patients. Efficacy and tolerability of boceprevir-based triple therapy are suboptimal, particularly in the most difficult to cure patient population. Orv. Hetil., 2016, 157(34), 1366-1374.

[Liver failure a la Eastern Europe]. / Májelégtelenség kelet-európai módra.

The use of valeriana was underplayed at the beginning of the 20th century because of its addictive and side effects. The 38-year-old woman, mother of a 20-month-old child from Eastern Europe, was treated with liver insufficiency and vascular, parenchymal decompensated cirrhosis needing plasmapheresis for the first time in our hospital. In case history, abusus of aethyl-alcohol and valeriana was found to be as toxic agent which was treated as the etiologic factor of the liver disease and liver failure. After intensive and conservative treatment her status was stabilised, during the follow-up she had no signs and symptoms, the laboratory results tend to be in normal range. Half year after her hospitalization intensive care treatment was necessary abroad due to gastric bleeding. In the background the histology of gastric biopsy taken during gastroscopic examination showed gastric sigillocellular carcinoma in our hospital. Total gastrectomy, omentectomy, lymphadenectomy were performed, the tumor was removed and she received cytostatic treatment. The use of valeriana and aethyl-alcohol is supposed to have a potential effect on tumorgenesis and on the increase of toxicity.

Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA.

BACKGROUND: The Abbott RealTime HCV assay for quantitative detection of HCV RNA has recently been introduced. OBJECTIVES: In this study, the performance of the Abbott RealTime HCV assay was evaluated and compared to the COBAS AmpliPrep/COBAS TaqMan HCV test. STUDY DESIGN: Accuracy, linearity, interassay and intra-assay variations were determined, and a total of 243 routine clinical samples were investigated. RESULTS: When accuracy of the new assay was tested, the majority of results were found to be within +/-0.5 log(10) unit of the results obtained by reference laboratories. Determination of linearity resulted in a quasilinear curve up to 1.0 x 10(6)IU/ml. The interassay variation ranged from 15% to 32%, and the intra-assay variation ranged from 5% to 8%. When clinical samples were tested by the Abbott RealTime HCV assay and the results were compared with those obtained by the COBAS AmpliPrep/COBAS TaqMan HCV test, the results for 93% of all samples with positive results by both tests were found to be within +/-1.0 log(10) unit. The viral loads for all patients measured by the Abbott and Roche assays showed a high correlation (R(2)=0.93); quantitative results obtained by the Abbott assay were found to be lower than those obtained by the Roche assay. CONCLUSIONS: The Abbott RealTime HCV assay proved to be suitable for use in the routine diagnostic laboratory. The time to results was similar for both of the assays.

Rapid quantification of hepatitis B virus DNA by automated sample preparation and real-time PCR.

Monitoring of hepatitis B virus (HBV) DNA in serum by molecular methods has become the standard for assessment of the replicative activity of HBV. Several molecular assays for the detection and quantification of HBV DNA have been described. However, they usually lack automated sample preparation. Moreover, those assays, which are based on PCR, are limited by a short dynamic range (2 to 3 log units). In the present study, the use of RealArt HBV LC PCR Reagents in conjunction with automated extraction on the COBAS AMPLIPREP analyzer was evaluated. Members of an HBV proficiency program panel were tested; linearity, interassay, and intra-assay variations were determined. The performance of the assay in a routine clinical laboratory was evaluated with a total of 117 clinical specimens. When members of the HBV proficiency program panel were tested by the new molecular assay, the results were found to be within +/-0.5 log unit of the results obtained by reference laboratories. Determination of linearity resulted in a quasilinear curve over more than 6 log units. The interassay variation of the RealArt HBV LC PCR Reagents by use of the automated sample preparation protocol ranged from 16 to 73%, and the intra-assay variation ranged from 9 to 40%. When clinical samples were tested by the new assay with the automated sample preparation protocol and the results were compared with those obtained by the COBAS AMPLICOR HBV MONITOR Test with manual sample preparation, the results for 76% of all samples with positive results by both tests were found to be within +/-0.5 log unit and the results for another 18% were found to be within between 0.5 and 1.0 log unit. In conclusion, the real-time PCR assay with automated sample preparation proved to be suitable for the routine molecular laboratory and required less hands-on time.

Evaluation of automated sample preparation and quantitative PCR LCx assay for determination of human immunodeficiency virus type 1 RNA.

Efforts have been made to achieve full automation of molecular assays for quantitative detection of human immunodeficiency virus type 1 (HIV-1). In the present study, the Abbott LCx HIV RNA Quantitative assay was evaluated in conjunction with automated HIV-1 RNA extraction on the MagNA Pure LC instrument and compared to the conventional LCx HIV RNA Quantitative assay, which uses a manual nucleic acid extraction protocol. Accuracy, linearity, and interassay and intra-assay variations were determined. The performance of the assay in a routine clinical laboratory was tested with a total of 105 clinical specimens. When the accuracy of the LCx HIV RNA Quantitative assay with the automated sample preparation protocol was tested, all results were found to be within +/- 0.5 log unit of the expected results. Determination of linearity resulted in a quasilinear curve over 3.5 log units. For determination of interassay variation, coefficients of variation were found to be between 21 and 66% for the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and between 10 and 69% for the LCx HIV RNA Quantitative assay with manual sample preparation. For determination of intra-assay variation, coefficients of variation were found to be between 7 and 25% for the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and between 7 and 19% for the LCx HIV RNA Quantitative assay with manual sample preparation. When clinical samples were tested by the LCx HIV RNA Quantitative assay with the automated sample preparation protocol and the results were compared with those of the LCx HIV RNA Quantitative assay with manual sample preparation, 95% of all positive results were found to be within +/- 0.5 log unit. In conclusion, the assay with automated sample preparation proved to be suitable for use in the routine diagnostic laboratory and required significantly less hands-on time.

Hepatitis C virus genotypes in Hungarian and Austrian patients with chronic hepatitis C.

Hepatitis C virus (HCV) genotypes are relevant to epidemiological questions, vaccine development, and clinical management of chronic HCV infection. The aim of this study was to determine HCV genotypes of South Hungarian and Southeast Austrian patients with chronic hepatitis C. Results were obtained by the largely automated TruGene HCV 5'NC Genotyping Kit (Visible Genetics, Toronto, Ontario) and by phylogenetic analysis. All of the 20 Hungarian patients and 15 out of 20 Austrian patients were infected with genotype 1. The remaining Austrian patients were infected with genotypes 3 or 2. With the commercially available assay, it was not possible to determine the HCV subtype in a total of three patients. The TruGene HCV 5'NC Genotyping assay for the determination of HCV genotypes proved to be useful for a high-throughput routine diagnostic laboratory.