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Current hepatitis C virus (HCV) therapies are associated with significant adverse events and less-than-ideal sustained virologic response (SVR) rates in genotype 1 patients. The current standard of care, a combination of pegylated interferon and ribavirin, will likely remain a key component of the treatment regimen for years to come. Multiple new drugs are currently in development and are expected to be approved for use in the United States and/or European Union by 2011 at the earliest. Future therapies will include novel interferons, ribavirin analogues, NS3 HCV protease inhibitors, NS5b HCV polymerase inhibitors, cyclophilin inhibitors, and other novel agents. There is hope that multiple new drugs will be approved over the following 4–10 years to provide alternative treatment choices, improved SVR rates, and reductions in adverse events. However, a number of barriers must be overcome prior to the acceptance of these drugs, involving, but not limited to, their toxicity, viral resistance, optimal dose, duration, and their efficacy and safety in patients with unmet needs.

Sierpińska Lidia, Jankowska Ewa. School adolescents' knowledge concerning hepatitis C virus (HCV). Journal of Education, Health and Sport. 2017;7(1):11-27. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.229140 http://ojs.ukw.edu.pl/index.php/johs/article/view/4133 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 754 (09.12.2016). 754 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 05.12.2016. Revised 20.12.2016. Accepted: 31.12.2016. Wiedza młodzieży szkolnej na temat zakażenia wirusem HCV School adolescents' knowledge concerning hepatitis C virus (HCV) Lidia Sierpińska1, Ewa Jankowska2 1 1 Wojskowy Szpital Kliniczny z Polikliniką SP ZOZ w Lublinie 1 Military Clinical Hospital with Polyclinic, Independent Public Health Care Unit, Lublin 2 Studenckie Koło Naukowe Wyższej Szkoły Biznesu i Przedsiębiorczości w Ostrowcu Świętokrzyskim Students' Scientific ...

Although Australian epidemiology of HBV and HCV has been well described for populations groups at higher risk, but the information available for groups generally considered to be lower risk is much more limited. An understanding of the prevalence of these infections and their risk factors in antenatal women is important to guide testing policy and practice. A study was therefore conducted of the epidemiology of hepatitis B and hepatitis C infection in women. In addition, women were asked about their experience with antenatal testing. A total of 516 women participated in the survey, of these 479 (95%) women had been tested for HCV antibodies .The prevalence of HCV antibodies was 4% overall, and 2% among women who were unaware of their HCV status prior to their antenatal test. A history of injecting drug use and residing with a HCV positive person were significantly associated with HCV infection in multivariate analyses. HBV testing was conducted in 468 (99.6%) of women, and the overall prevalence was 2%. Risk factors identified were birthplace in countries of South East Asia. Women were asked about their perception of antenatal testing and pre-test information. Nearly a third (143, 30.5%) of women who had been tested for HCV infection either said that they did not know whether they had been tested, or said that they had declined testing. The corresponding proportion for HBV infection was 28.8% (135). Over 65% and 66% of women said that had not received any information about testing for HCV and HBV respectively. The finding that virtually all antenatal women were being tested for HCV was in contrast to government and non-government organisation policies of selective screening in place during the study period. Of concern was the substantial proportion of women who were tested despite reporting that they had declined their clinician s offer to test for HCV and HBV, and the large number of women who reported an absence of pre-test information. Women who said they had received information reported the delivery and ...

Although it is well established that hepatitis C virus (HCV) entry into hepatocytes depends on clathrin-mediated endocytosis, the possible roles of clathrin in other steps of the viral cycle remain unexplored. Thus, we studied whether cell culture-derived HCV (HCVcc) exocytosis was altered after clathrin interference. Knockdown of clathrin or the clathrin adaptor AP-1 in HCVccinfected human hepatoma cell cultures impaired viral secretion without altering intracellular HCVcc levels or apolipoprotein B (apoB) and apoE exocytosis. Similar reductions in HCVcc secretion were observed after treatment with specific clathrin and dynamin inhibitors. Furthermore, detergent-free immunoprecipitation assays, neutralization experiments, and immunofluorescence analyses suggested that whereas apoE associated with infectious intracellular HCV precursors in endoplasmic reticulum (ER)-related structures, AP-1 participated in HCVcc egress in a post-ER compartment. Finally, we observed that clathrin and AP-1 knockdown altered the endosomal distribution of HCV core, reducing and increasing its colocalization with early endosome and lysosome markers, respectively. Our data support a model in which nascent HCV particles associate with apoE in the ER and exit cells following a clathrin-dependent transendosomal secretory route ; This work was supported in part by the following grants: (i) grant SAF2010-21249 from the Ministerio de Ciencia e Investigación (MCI) to M.L.-C.; (ii) grant SAF2010-19270 from the MCI to P.G.; (iii) Marie Curie Career Integration grant PCIG-9-GA-2011-293664 from the European Union 7th Framework Programme for Research to P.G.; and (iv) FEDER funds via the Spanish Government to projects PI10/00101 and PI13/ 00159, from the Instituto de Salud Carlos III (ISCIII) Fondo de Investigaciónes Sanitarias (FIS) and the Fundación Mutua Madrileña, to P.L.M. I.B. was financially supported by Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), V.G. by FIS (PI10/00101), and F.M.-J. by ISCIII and Fundación para la Investigación Biomédica (FIB) del Hospital Universitario de la Princesa

Although it is well established that hepatitis C virus (HCV) entry into hepatocytes depends on clathrin-mediated endocytosis, the possible roles of clathrin in other steps of the viral cycle remain unexplored. Thus, we studied whether cell culture-derived HCV (HCVcc) exocytosis was altered after clathrin interference. Knockdown of clathrin or the clathrin adaptor AP-1 in HCVccinfected human hepatoma cell cultures impaired viral secretion without altering intracellular HCVcc levels or apolipoprotein B (apoB) and apoE exocytosis. Similar reductions in HCVcc secretion were observed after treatment with specific clathrin and dynamin inhibitors. Furthermore, detergent-free immunoprecipitation assays, neutralization experiments, and immunofluorescence analyses suggested that whereas apoE associated with infectious intracellular HCV precursors in endoplasmic reticulum (ER)-related structures, AP-1 participated in HCVcc egress in a post-ER compartment. Finally, we observed that clathrin and AP-1 knockdown altered the endosomal distribution of HCV core, reducing and increasing its colocalization with early endosome and lysosome markers, respectively. Our data support a model in which nascent HCV particles associate with apoE in the ER and exit cells following a clathrin-dependent transendosomal secretory route. ; This work was supported in part by the following grants: (i) grant SAF2010-21249 from the Ministerio de Ciencia e Investigación (MCI) to M.L.-C.; (ii) grant SAF2010-19270 from theMCIto P.G.; (iii) Marie Curie Career Integration grant PCIG-9-GA-2011-293664 from the European Union 7th Framework Programme for Research to P.G.; and (iv) FEDER funds via the Spanish Government to projects PI10/00101 and PI13/00159, from the Instituto de Salud Carlos III (ISCIII) Fondo de Investigaciónes Sanitarias (FIS) and the Fundación Mutua Madrileña, to P.L.M. I.B. was financially supported by Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas (CIBERehd), V.G. by FIS (PI10/00101), and F.M.-J. by ISCIII and Fundación para la Investigación Biomédica (FIB) del Hospital Universitario de la Princesa. ; Peer Reviewed

Million people worldwide are affected by the hepatitis C virus (HCV). The highest incidence of illness was between 1945 and 1975. It was also estimated that 70% of those people were not tested for the disease. Most recent treatment concepts are safe, highly effective and have a vital public health influence by achieving a viral constant response in a significant proportion of treated patients. It helps reduce liver fibrosis, liver cancer risk and dissemination. With its increased population incidence, HCV becomes a serious public health problem. This review discusses the current literature in this field in terms of the importance of screening of HCV, follow-up, treatment and includes considerations in specific populations such as patients with cirrhosis, with HIV/HCV co-infection, patients with HBV/HCV co-infection and with renal damage

10 pages, 2 figures, 6 tables. ; The addition of ribavirin to alpha interferon therapy significantly increases response rates for patients with chronic hepatitis C virus (HCV) infection, but ribavirin's antiviral mechanisms are unknown. Ribavirin has been suggested to have mutagenic potential in vitro that would lead to "error catastrophe," i.e., the generation of nonviable viral quasispecies due to the increment in the number of mutant genomes, which prevents the transmission of meaningful genetic information. We used extensive sequence-based analysis of two independent genomic regions in order to test in vivo the hypothesis that ribavirin administration accelerates the accumulation of mutations in the viral genome and that this acceleration occurs only when HCV replication is profoundly inhibited by coadministered alpha interferon. The rate of variation of the consensus sequence, the frequency of mutation, the error generation rate, and the between-sample genetic distance were measured for patients receiving ribavirin monotherapy, a combination of alpha interferon three times per week plus ribavirin, or a combination of alpha interferon daily plus ribavirin. Ribavirin monotherapy did not increase the rate of variation of the consensus sequence, the mutation frequency, the error generation rate, or the between-sample genetic distance. The accumulation of nucleotide substitutions did not accelerate, relative to the pretreatment period, during combination therapy with ribavirin and alpha interferon, even when viral replication was profoundly inhibited by alpha interferon. This study strongly undermines the hypothesis whereby ribavirin acts as an HCV mutagen in vivo. ; This work is part of the activities of the VIRGIL European Network of Excellence on Antiviral Drug Resistance, supported by a grant (LSHM-CT-2004-503359) from the Priority 1 "Life Sciences, Genomics and Biotechnology for Health" program in the 6th Framework Programme of the European Union. The drugs were provided by Schering-Plough Research International, and the ribavirin and HCV RNA assays were funded by an unrestricted grant from Schering- Plough Research Institute. ; Peer reviewed

Qiagen, Germany ; German Ministry of Health ; National Reference Centre for Tropical Infections at the Bernhard Nocht Institute ; European Union ; EU: SSPE-CT-2005-022639 ; BackgroundDetection and quantification of hepatitis C virus (HCV) RNA is integral to diagnostic and therapeutic regimens. All molecular assays target the viral 5'-noncoding region (59-NCR), and all show genotype-dependent variation of sensitivities and viral load results. Non-western HCV genotypes have been under-represented in evaluation studies. An alternative diagnostic target region within the HCV genome could facilitate a new generation of assays.Methods and FindingsIn this study we determined by de novo sequencing that the 3'-X-tail element, characterized significantly later than the rest of the genome, is highly conserved across genotypes. To prove its clinical utility as a molecular diagnostic target, a prototype qualitative and quantitative test was developed and evaluated multicentrically on a large and complete panel of 725 clinical plasma samples, covering HCV genotypes 1-6, from four continents (Germany, UK, Brazil, South Africa, Singapore). To our knowledge, this is the most diversified and comprehensive panel of clinical and genotype specimens used in HCV nucleic acid testing (NAT) validation to date. The lower limit of detection (LOD) was 18.4 IU/ml (95% confidence interval, 15.3-24.1 IU/ml), suggesting applicability in donor blood screening. The upper LOD exceeded 10(-9) IU/ml, facilitating viral load monitoring within a wide dynamic range. In 598 genotyped samples, quantified by Bayer VERSANT 3.0 branched DNA (bDNA), X-tail-based viral loads were highly concordant with bDNA for all genotypes. Correlation coefficients between bDNA and X-tail NAT, for genotypes 1-6, were: 0.92, 0.85, 0.95, 0.91, 0.95, and 0.96, respectively; X-tail-based viral loads deviated by more than 0.5 log10 from 5'-NCR-based viral loads in only 12% of samples (maximum deviation, 0.85 log10). The successful introduction of X-tail NAT in a Brazilian laboratory confirmed the practical stability and robustness of the X-tail-based protocol. The assay was implemented at low reaction costs (US$8.70 per sample), short turnover times (2.5 h for up to 96 samples), and without technical difficulties.ConclusionThis study indicates a way to fundamentally improve HCV viral load monitoring and infection screening. Our prototype assay can serve as a template for a new generation of viral load assays. Additionally, to our knowledge this study provides the first open protocol to permit industry-grade HCV detection and quantification in resource-limited settings.