Tzukuan is an HBV-, HCV-, HDV- endemic township in southern Taiwan. Based on a mass screening on 2909 residents age of 45 years or more in 1997, the prevalence rates of HBsAg and anti-HCV were 12.8% and 41.6% respectively. Of HBsAg carriers, 15.3% were positive for anti-HDV. Tzukaun was divided into coastal area and inland area. The prevalence of anti-HCV of coastal area was two times higher than that of inland area (61.4% v.s. 29.1%) and genotype 1b and 2a are the main two subtypes. We wish to find the causes of discrepancy in these nearby areas by phylogenetic analysis. Stratified by the living areas, coastal or inland, 27 samples were picked up (ingroup). HCV sequence of NS5B region could be detected by RT-PCR then a nested PCR in eight males and ninteen females with mean age of 54.8 years old (range: 45-70). None of these 27 residents came from the same family. Another 10 HCV infected persons whose living townships also in southern Taiwan but other than Tzukuan were enrolled as local controls. From GenBank, 30 different HCV isolates were included. Phylogenic analysis unequivocally confirmed the simultaneous spread of two different HCV strains in this township clusters according to their subtypes were noted. A trend of the spreading from coastal to land area or an ultra-aggregation phynomenon which according to their living area, as we suspected, were not noted between Tzukuan¡¦s residents. In ingroup, the short genetic distance between the isolates of C hepatitis virus which came from different villages might be caused from the wide-spreading of HCV in this endemic area (the maximal and minimal genetic distance in 1b or 2a isolates are 0.0869 vs. 0.0098 and 0.0996 vs. 0.0334). Besides, according to the contacting history to foreigner by our aborigine tribes, from genebank, all isolates from different countries were included and three possible origins of HCV genotype 1b were noted in Tzukuan. All these findings might be caused from frequently HCV inflow in this endemic area and wide-spreading of HCV between different countries.

Chronic liver disease is an important disease which affects national healthy in Taiwan. Hepatitis B or C virus infection is strongly relative to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. However, the early effective treatment can decrease the progression of liver cirrhosis and hepatocellular carcinoma and increase the recovery rate. In order to promote the health care quality for the patients with hepatitis, Bureau of National Health Insurance (BNHI) implemented the ¡§Enhance Hepatitis B or C Health Care Program¡¨ in October of 2003. The new policy sets up the standard treatment models and pay medical costs to encourage the patients to participate this program and fit cost-effectiveness. Therefore, aims of the study are to estimate the effects of the new policy on health care utilization and expenditures for the patients with hepatitis B or C. The study used the database from Bureau of National Health Insurance (BNHI) in 2002 and 2004. The study sample is the patients with hepatitis B or C who enrolled the program from January to June in 2004. We compared the differences of health care utilization and expenditures with these statistics in 2002. Besides, we also analyzed the difference in the characteristics of the patients and hospitals. In health care utilization, we found that number of visits was increased but interval between visits was decreased. Total costs, costs of treatments, prescriptions, total claim amount, and averages of prescription costs in health care expenditures were all increased significantly after the new policy implemented. Otherwise, there were not different on health care utilization and expenditures between different gender and level of the hospitals. On the other hand, there were significantly correlation of ages and number of comorbility. It means that the patients¡¦ ages are older, and their number of visits and total costs are higher but interval between visits is shorter than younger. Furthermore, number of comorbility increases and then interval between visits become short. The new policy certainly affects the health care utilization and expenditures of patients with hepatitis B or C. Implementing the new program can encourage patients adopt treatment actively and physicians have standard treatment protocols to follow. Understanding the changes on health care utilization and expenditures can give a health care guideline of cost-effectiveness. In conclusion, the results can provide the information about payments on patients with hepatitis to BNHI and then use it to be a basis after the new program implemented. Moreover, other countries also can evaluate the implementation of the new policy based on our results.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009. / Härtill 6 uppsatser.

Düsseldorf, University, Thesis (doctoral), 2000.

The hepatitis C virus (HCV) disproportionately affects the prison population. Studies demonstrate that healthcare provider knowledge of HCV risk factors is insufficient and many individuals are not aware that they are HCV positive. Early identification of HCV status can prompt early treatment and avoidance of complications that contribute to poor outcomes resulting in chronic disease progression. This doctor of nursing practice (DNP) project addresses provider identification of HCV risk factors at initial inmate intake to prison and whether providers obtained HCV testing based on guidelines from the Centers for Disease Control and Prevention (CDC). The principal investigator (PI) conducted a retrospective medical record review at Arizona State Prison Complex (ASPC) Lewis focusing on initial inmate intake forms identifying two of the CDC risk factors for HCV: drug abuse and tattoos; and ascertaining if a providers ordered a HCV test if inmates had one or both of these risk factors. The PI reviewed 51 randomly selected medical records; 40 records met inclusion criteria of 1) inmates who had an initial inmate intake evaluation occurring from 1 October 2013 to 1 October 2014 and 2) documentation of positive HCV risk factors. Analysis of the records showed a mean inmate age of 26.78 years with a variable racial distribution. The risk factor of tattooing was present in 37 (92.5%) of records reviewed and the risk factor of intravenous drug use (IVDU) was present in 7 (17.5%). Only 4 (10%) records of inmates with positive risk factors had a HCV test ordered by the provider: One physician (n=2) and one nurse practitioner (n=2). This project demonstrated a gap in HCV testing in the presence of risk factors in the inmate population at ASPC Lewis which is consistent with studies in the general population. This study does not identify any reasons for this consistency, but raises questions for future studies focused on provider knowledge, education and the institution of HCV testing protocols. This DNP project provides the foundation for a future full quality improvement Plan-Do-Study-Act based project aimed at educating providers about HCV testing according to CDC (2013a) guidelines and subsequently re-evaluating their HCV test ordering practices.

Πραγματοποιήσαμε πολυσταδιακή δειγματοληπτική έρευνα, προκειμένου να μελετήσουμε τον επιπολασμό και τις οδούς μετάδοσης της ηπατίτιδας Β και C στο γενικό πληθυσμό του Νομού Αχαΐας. Για το σκοπό αυτό εξετάσαμε αντιπροσωπευτικό δείγμα 1500 ατόμων χρησιμοποιώντας τρίτης γενιάς αντιδραστήρια. Δείκτες HBV μόλυνσης διαπιστώθηκαν σε 339 άτομα (22,6%) με επιπολασμό anti-HBc αντισωμάτων 21,6% (95%CI:19,5-23,8) και HBsAg αντιγόνου 2,1% (95%CI:1,5-3). Anti-HCV θετικά αντισώματα διαπιστώθηκαν σε 8 άτομα με ELISA-3 (0,5%, 95%CI:0,2-1,1), από τα οποία 5 (62,5%) επιβεβαιώθηκαν με LIA-3 και 3 (37,5%) είχαν PCR θετική. Συλλοίμωξη ή παρελθούσα μόλυνση και από τους δύο ιούς ανιχνεύτηκε σε 5 άτομα (0,3%). Από τη στατιστική σύγκριση που έγινε διαπιστώθηκε αυξημένη HBV μόλυνση σε στατιστικά σημαντικό βαθμό στους άνδρες, στους πλέον ηλικιωμένους, στους εγγάμους/διαζευγμένους/χήρους, σε άτομα χαμηλότερου επιπέδου μόρφωσης, με >2 παιδιά, με συγκατοίκηση <2 άτομα καθώς και στις ορεινές και αγροτικές περιοχές έναντι των αστικών και πεδινών. Επίσης, το θετικό περιβάλλον, η κατάχρηση αλκοόλ, η ύπαρξη σεξουαλικών σχέσεων και η μη χρήση προφυλακτικού τόσο με τον περιστασιακό όσο και με το μόνιμο σύντροφο ήταν παράγοντες κινδύνου της μόλυνσης από ιό Β. Αντίθετα, δε βρέθηκε στατιστικώς σημαντική διαφορά HBV μόλυνσης σε σχέση με τις μεταγγίσεις και τη νοσηλεία >1d. Από την άποψη της επαγγελματικής κατανομής της Β μόλυνσης, ιδιαίτερα επιβαρημένη ήταν η αγροτική και η εργατική τάξη. Πάντως, από την πολυπαραγοντική ανάλυση που ακολούθησε μόνο το άρρεν φύλο (ΣΚ 4,1, 95%CI:2,4-7,1), η αυξημένη ηλικία (≥30 ετών ΣΚ 9, 95%CI:4,2-19,4) και το θετικό περιβάλλον (ΣΚ 1,3, 95%CI:0,9-1,8) είχαν ανεξάρτητη σχέση με την HBV μόλυνση. Η γενετήσια και η ενδοοικογενειακή οδός αποτελούσαν τους συχνότερους τρόπους διασποράς του ιού Β, ενώ η παρεντερική οδός ήταν η κυρίαρχη στην μετάδοση του ιού C. Χρόνια ηπατίτιδα Β διαπιστώθηκε στο 9,5% των HBsAg θετικών που ελέγχτηκαν στο Τμήμα Λοιμώξεων (σε κανέναν δεν ανιχνεύτηκε HBV-DNA ιαιμία), ενώ το 60% των επιβεβαιωμένων anti-HCV θετικών έπασχε από χρόνια ηπατίτιδα C. Εμβολιασμό έναντι της ηπατίτιδας Β δήλωσαν 183 άτομα (12,2%), στο 85,8% μαθητές και H.C.W, και anti-HBs>10mIU/ml ανιχνεύτηκαν στο 83,6%. Τέσσερα άτομα (2,2% των εμβολιασθέντων) παρουσίασαν και δείκτες παρελθούσας HBV μόλυνσης. Η «αποτυχία» του εμβολίου υπολογίστηκε στο 7,5%. Οι άνδρες, παρά τον τετραπλό κίνδυνο μόλυνσης, εμβολιάζονταν σε μικρότερο βαθμό συγκριτικά με τις γυναίκες, ενώ δεν υπήρχε στατιστικώς σημαντική διαφορά εμβολιασμού μεταξύ αυτών που είχαν θετικό και αρνητικό περιβάλλον. Συμπερασματικά, ο Νομός Αχαΐας κατατάσσεται στις ενδιάμεσης ενδημικότητας περιοχές όσον αφορά στην ηπατίτιδα Β και στις χαμηλής ενδημικότητας όσον αφορά στην ηπατίτιδα C. Οι κύριοι οδοί μετάδοσης είναι η γενετήσια και η ενδοοικογενειακή για τον ιό Β και η παρεντερική για τον ιό C. Παρά την πολύ μικρή συχνότητα στο γενικό πληθυσμό και λόγω του υψηλού ποσοστού μετάπτωσης σε χρονιότητα, η ηπατίτιδα C παίζει όχι μόνο εξίσου σημαντικό αλλά ίσως και πρωταγωνιστικό ρόλο στη νοσηρότητα από χρόνια ιογενή ηπατοπάθεια στην περιοχή μας. Ειδικά για την ηπατίτιδα Β, η υιοθέτηση του μαζικού εμβολιασμού θα αλλάξει το επιδημιολογικό τοπίο, αλλά χρειάζεται παράλληλα πιο ικανοποιητική κάλυψη των ομάδων υψηλού κινδύνου. / A community-based survey was conducted using the multistage random sampling method, in order to determine the prevalence and routes of transmission of hepatitis B and C in the general population of Achaia region in the Southwestern Greece. For this purpose we examined a representative sample of 1500 individuals using third generation assays. HBV infection markers were detected in 339 subjects (22,6%) with anti-HBc prevalence 21,6% (95%CI:19,5-23,8) and HBsAg prevalence 2,1% (95%CI:1,5-3). Anti-HCV antibodies were detected in 8 subjects with ELISA-3 (0,5%, 95%CI:0,2-1,1), 5 of which (62,5%) were confirmed with LIA-3 and 3 (37,5%) were HCV-RNA positive. Dual or past infection with both viruses was detected in 5 subjects (0,3%). Male sex, older age, married/divorced/widowed family status, lower level of education, more than two children, cohabitation with less than two persons, positive environment, alcohol abuse, sex, absence of condom prophylaxis during sexual intercourse with single or multiple partners were all risk factors for HBV infection (statistically significant). On the contrary, there was not significant difference between HBV-negative and HBVinfected individuals when transfusions or hospitalization >1d were concerned. Workers and people in the agricultural sector were particularly affected. Nevertheless, multivariate statistical analysis revealed that male sex (RR 4,1, 95%CI:2,4-7,1), older age (≥30y RR 9, 95%CI:4,2-19,4) and positive environment (RR 1,3, 95%CI:0,9-1,8) were the only independently associated with HBV infection risk factors. Sexual and intrafamiliar exposure were the commonest ways for HBV transmission, while percutaneous exposure was the main route for HCV transmission. Chronic hepatitis B was diagnosed in 9,5% of HBsAg carriers who were examined by the physicians of the Department of Infectious Diseases (nobody was HBV-DNA positive), while 60% of those with confirmed anti-HCV antibodies had chronic hepatitis C. 183 subjects declared B immunization (12,2%), mostly pupils and health care workers (85,8%), and anti-HBs>10mIU/ml were detected in 83,6% of them. Four (2,2%) had, also, positive markers of past HBV infection. Vaccination failure was estimated at 7,5%. Men, despite their fourfold risk of infection, were immunized at a lower rate than women, while there was not significant difference in immunization rate between those with positive and negative environment. In conclusion, Achaia region can be classified as an intermediate HBV and a low HCV endemicity area. The main routes of HBV and HCV transmission are the sexual/intrafamiliar and percutaneous respectively. Despite the very low prevalence of hepatitis C and due to its higher range of chronicity, the number of chronically HBV and HCV infected in the general population seem to be comparable and, even, hepatitis C can play a leading role in chronic viral liver disease in our region. As far as hepatitis B is concerned, the adoption of mass immunization programmes will alter the epidemiological landscape and this should be especially encouraged in persons belonging to high risk groups.

Hepatitis C (HCV) is an infectious disease of the liver which affects more than 250,000 Canadians; the majority of those living with the disease have experience with injection drug use. Treatment for HCV involves a strict protocol, has only a 50% success rate and has harsh side effects. Interest in HCV treatment among people who use drugs is high, but actual uptake of treatment remains low. The objective of this research was to explore the barriers to accessing HCV treatment for individuals who were accessing methadone. A mixed methods approach was used; a cross sectional survey and an in-depth interview were administered to clients of a methadone maintenance program. The two sets of data identified three main barriers to HCV treatment; stigma, the toxicity of treatment, and day-to-day struggles. Future research should be conducted to further explore how stigma guides decisions around HCV treatment, particularly in a methadone treatment setting.

No description available.

Viral proteases are often considered to be attractive drug targets because of their crucial function in the viral replication machinery. In order to increase our knowledge of these important targets and to contribute to the discovery and development of new antiviral drugs, the proteases from hepatitis C virus (HCV) and human cytomegalovirus (HCMV) have been produced and their interactions with inhibitors and fragments have been characterized, using enzyme inhibition and SPR biosensor based interaction assay. The structure activity relationships and the resistance profiles of a series of HCV NS3 protease inhibitors based on either P2 proline or phenylglycine residues were analyzed using wild type genotype 1a and the major resistant variants A156T and D168V. The observed susceptibility to substitutions associated with these resistance variants was concluded to depend on the P2 and the P1 residue, and not only on the P2 residue as previously had been suggested. In order to be able to evaluate how the potency of inhibitors is affected by genetic variation, their effect was evaluated on wild type NS3 from genotype 1a, 1b and 3a as well as on the resistant variant R155K from genotype 1a. To enable a comparison of the inhibitory effect on the enzyme variants, the compounds were analyzed under conditions optimized for each variant. VX-950 was found to be the least susceptible compound to resistance and genetic variation. A more detailed analysis showed that the kinetic and mechanistic features of the inhibitors were significantly different for the different genotypes. The reversible non covalent macrocyclic inhibitor ITMN 191 was revealed to have favorable kinetics for all three genotypes. This is an advantage for the design of broad spectrum drugs. A fragment based procedure for identifying and validating novel scaffolds for inhibitors of HCMV protease was established. It identified fragments that may serve as starting points for the discovery of effective inhibitors against this challenging target.   The procedures developed for the evaluation and identification of novel HCV NS3 and HCMV protease inhibitors have contributed to a deeper understanding of protease-inhibitor interactions that is expected to have an impact on the design of novel antiviral drugs.

<p>Dengue viruses (DENV) are mosquito&#8208;borne flaviviruses that pose a continued and growing threat to global health. There are estimated to be 390 million DENV infections each year, and because there is no vaccine or approved therapeutic treatment, developing a small&#8208;molecule treatment is imperative. Possible small&#8208;molecule drug therapies for DENV could be immune system modulators, inhibitors of DENV&#8208;required host factor, or inhibitors of a viral gene product. In this study, we chose to take the latter approach and focused our drug discovery efforts on the most highly conserved flaviviral protein, non&#8208;structural protein 5 (NS5). NS5 contains two major domains, each with different enzymatic activities. The N&#8208;terminus has methyltransferase activity, and the C terminus, an RNA&#8208;dependent RNA polymerase (RdRp). The activities of both domains are purine&#8208;dependent, and therefore both domains contribute to the purine&#8208;binding properties of NS5. Inhibition of either of these domains in NS5 results in inadequate propagation of DENV, and the purine&#8208;binding domains present ideal drug targets for disrupting these activities. These factors make NS5 protein an ideal candidate target for our small&#8208;molecule library screen.</p><p>A high&#8208;throughput fluorescence&#8208;based screen was employed to identify anti&#8208;DENV compounds based on their ability to competitively bind NS5. The screen was performed by binding green fluorescent protein NS5 fusion protein (GFP&#8208;NS5) to immobilized ATP resin, and then performing parallel elutions using over 3,000 distinct compounds. One compound in particular, HS&#8208;205020, was able to competitively elute GFP&#8208;NS5 from the ATP resin and also exhibited antiviral activity in both the U937+DCSIGN human monocyte cell line and BHK&#8208;21 cells. Additionally, HS&#8208;205020 was able to inhibit DENV NS5 RNA polymerase activity in vitro. HS&#8208;205020 is chemically distinct from the majority of previously reported NS5 inhibitors, which are nucleoside analogs that can cause severe toxicity in animal studies. In contrast, over the concentration range that produced anti&#8208;DENV effects, HS&#8208;205020 showed comparable viabilities to ribavirin, an FDA approved hepatitis C virus (HCV) therapeutic. These findings support HS&#8208;205020 as a potential dengue antiviral candidate, and its chemical scaffold represents as an ideal starting compound for future structure&#8208;activity relationship studies.</p> / Dissertation