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Managing HCV infection in pediatric age group: Suggested recommendations  [cached]
Danish Fazal,Koul Salman,Subhani Fazal,Rabbani Ahmed
Saudi Journal of Gastroenterology , 2010,
Abstract: Hepatitis C virus (HCV) infection in children is different from the adult infection in many ways, like natural course of the disease; duration, therapeutic response and side effects profile of the drug therapy; and prognosis. Special considerations include consideration on what could be the appropriate time to investigate a suspected child, when to institute drug therapy and how to prevent vertical transmission. Although over the past one decade many landmark studies have greatly increased our insight on this subject, yet we are far from developing a consensus statement. In this article, a concise yet comprehensive review of HCV infection in children - diagnosis and treatment - is given, followed by suggested recommendations at the end. It is hoped that these recommendations will help develop local guidelines on this subject.
A Practical Approach to Managing Spreadsheet Risk in a Global Business  [PDF]
Thomas Lemon,Ewen Ferguson
Computer Science , 2010,
Abstract: Spreadsheets are used extensively within today's organisations. Although spreadsheets have many benefits, they can also present a significant risk exposure, requiring appropriate management. Protiviti has worked with a number of organisations, ranging in size up to huge multi-nationals, to help them build appropriate spreadsheet governance frameworks, including the design and implementation of policies, minimum design standards, control processes, training and awareness programmes and the consideration and implementation of spreadsheet management tools. This paper presents a case-study explaining the practical and pragmatic approach that was recently taken to control spreadsheet risk at one of Protiviti's clients - a global energy firm.
The Challenge of Managing Marine Biodiversity: A Practical Toolkit for a Cartographic, Territorial Approach  [PDF]
Carlo Nike Bianchi,Valeriano Parravicini,Monica Montefalcone,Alessio Rovere,Carla Morri
Diversity , 2012, DOI: 10.3390/d4040419
Abstract: An approach to the management of marine biodiversity was developed based on two levels of environmental diagnostics: (1) the characterization (to identify types), and (2) the evaluation (to define status and values). Both levels involve the production of maps, namely: (i) morphobathymetry and sedimentology; (ii) habitats; (iii) natural emergencies; (iv) degradation and risk; (v) weighted vulnerability; (vi) environmental quality; and, (vii) susceptibility to use. A general methodological aspect that must be stated first is the need of dividing the mapped area in territorial units corresponding to submultiples of the UTM grid and having different sizes according to the scale adopted. Territorial units (grid cells) are assigned to one of five classes of evaluation, ranging from high necessity of conservation or protection to non-problematic, unimportant or already compromised (according to the specific map) situations. Depending on the scale, these maps are suited for territorial planning (small scales, allowing for a synoptic view) or for administration and decision making (large scales, providing detail on local situations and problems). Mapping should be periodically repeated (diachronic cartography) to assure an efficient tool for integrated coastal zone management.
Lipid Metabolism and HCV Infection  [PDF]
Paul Targett-Adams,Steeve Boulant,Mark W. Douglas,John McLauchlan
Viruses , 2010, DOI: 10.3390/v2051195
Abstract: Chronic infection by hepatitis C virus (HCV) can lead to severe liver disease and is a global healthcare problem. The liver is highly metabolically active and one of its key functions is to control the balance of lipid throughout the body. A number of pathologies have been linked to the impact of HCV infection on liver metabolism. However, there is also growing evidence that hepatic metabolic processes contribute to the HCV life cycle. This review summarizes the relationship between lipid metabolism and key stages in the production of infectious HCV.
Interferon-λ in HCV Infection and Therapy ?  [PDF]
Nicole E. Pagliaccetti,Michael D. Robek
Viruses , 2010, DOI: 10.3390/v2081589
Abstract: Chronic infection with hepatitis C virus (HCV) is associated with significant liver disease and is therefore an important public health problem. The current standard-of-care therapy for chronic HCV infection consists of a combination of pegylated (PEG) interferon (IFN)-α and ribavirin. Although this therapy effectively generates a sustained viral response in approximately half of treated individuals, it is associated with significant hematological and neurological side effects. A new family of IFN-related proteins (IFN-λ1, 2, and 3; or alternately, IL-29, 28A, 28B, respectively) possesses properties that may make these cytokines superior to PEG-IFN-α for HCV therapy. Genetic studies have also implicated these proteins in both the natural and therapy-induced resolution of HCV infection. This review summarizes the basic aspects of IFN-λ biology, the potential role of these cytokines in HCV infection, and the outlook for their therapeutic application.
Rheumatoid Case with HCV Infection
Bita Behnava,Seyed-Moayed Alavian
Hepatitis Monthly , 2005,
Abstract: Case Presentation:A 46-year-old woman referred to our center due to abnormality in aminotransferase level during check up. She had a history of blood transfusion 12 years ago. Anti-HCV Ab by ELISA method and HCV RNA by RT-PCR were positive. HCV RNA by Amplicor HCV monitor test counted 800,000 IU/ml and the genotype was 3a by Specific Primer-Targeted Region Core method. Laboratory evaluation revealed: Hb 11.9 mg/dl, WBC 5000 /ml, platelet count 190,000/ ml, ALT 70 IU/ml, AST 65 IU/ml, Alk phosphatase 210, PT 13 second, total protein 7.2 g/dl, albumin 4 g/dl, gama globulin 1.6 g/dl, HBsAg negative and RF positive. She had a history of symmetrical polyarthritis of small joints of upper extremities and morning stiffness for 3 years ago and had been managed as rheumatoid arthritis (RA) since then. She was managed with corticosteroids and methotrexate. Are there any relations between RA disease and HCV infection?HCV-related ArthritisRheumatologic complications of HCV infection are common and include mixedcryoglobulinemia, vasculitis, Sjogren’s syndrome, arthritis and fibromyalgia(1, 2). There is a welldefined picture of arthritis associated with the presence of mixed cryoglobulinemia that consists of an intermittent mono or oligoarticular,nondestructive arthritis affecting large and mediumsize joints(1). 2% to 20% of HCV-infected patients experience arthritis and as 50% experience arthralgia(3)Clinical ManifestationsHCV-related arthritis (HCVra) commonly presents as rheumatoid-like, symmetrical inflammatory polyarthritis involving mainly small joints or less commonly as mono- or oligoarthritis of large joints. The joints involved in HCV-related arthritis are similar to RA(4). In about two thirds of the affected individuals, morning stiffness may be severe, resolving after more than an hour(5). Clinical picture of arthritis associated with the presence of mixed cryoglobulinemia in patients with HCV infection consists of an intermittent, mono or oligoarticular, nondestructive arthritis affecting large and medium size joints(1).What Are Differences Between True RA Disease and HCV-related Arthritis?Differentiation between true RA and HCVrelated arthritis may be difficult. HCV-related arthritis usually runs a relatively benign course that, in contrast to true RA, is typically nondeforming and is not associated with articular bony erosions(4). Furthermore, unlike classic RA, ESR is elevated only in about half of the patients and subcutaneous nodules are absent(5). Patients with HCV-related arthritis are seropositive for RF, but anti keratin antibodies (AKA) are a us
Antiphospholipid Syndrome and HCV Infection  [PDF]
M. El-sherif,S. El-Gamal,M.H. Bahgat,O. E. Al-Agroudy
Journal of Medical Sciences , 2001,
Abstract: The research work was conducted to investigate the issue of anti-cardiolipin antibodies (ACAs) and HCV infection, two groups of patients had been selected; the group I (HCV group) comprised 25 patients proved to have HCV infection by PCR test and group II (thrombotic group) comprised 25 patients presented with different thrombotic events. In addition, 25 subjects were selected as a control group. For all patients, estimation of ACA-IgG was done, where 2 samples were taken and the first (initial) sample was at the start of the work. With recent thrombosis, the initial sample was withdrawn before starting heparin. The second (follow-up) sample was taken at least 2 months after the initial one. Results showed that 40% (10 / 25) of group I cases have persistently elevated ACA-IgG and further 40% of them (4 / 25) have the propensity for thrombosis, which was rather predominantly venous in nature. Fifty two percent of unexplained thrombotic cases in group II are ACA-IgG positive; thus the anti-phospholipid syndrome (APS) can account for a good percentage of unexplained thrombosis. Also, there was a significant reduction in platelet count with the rise of ACA-IgG in both groups. Therefore, the laboratory evaluation of APS is suggested to pass in two steps, catching isolated thrombocytopenia, waiting for the assessment of the ACAs as a more specific marker. Finally we can concluded that, the APS is an important additional extra-hepatic feature of HCV and should be anticipated and considered in the differential diagnosis of the different systemic features of this common hepatotropic virus. Advice to screening for the presence of APS in cases with HCV infection by ACA-IgG to be early submitted for antiviral therapy, also we suggested a further work to evaluating its probable clearance after effective successful antiviral therapy.
Practical considerations for sensitivity analysis after multiple imputation applied to epidemiological studies with incomplete data
Vanina Héraud-Bousquet, Christine Larsen, James Carpenter, Jean-Claude Desenclos, Yann Le Strat
BMC Medical Research Methodology , 2012, DOI: 10.1186/1471-2288-12-73
Abstract: This approach aims to approximate inferences under a Missing Not At random (MNAR) mechanism by reweighting estimates obtained after multiple imputation where the weights depend on the assumed degree of departure from the MAR assumption.The method is illustrated with epidemiological data from a surveillance system of hepatitis C virus (HCV) infection in France during the 2001–2007 period. The subpopulation studied included 4343 HCV infected patients who reported drug use. Risk factors for severe liver disease were assessed. After performing complete-case and multiple imputation analyses, we applied the sensitivity analysis to 3 risk factors of severe liver disease: past excessive alcohol consumption, HIV co-infection and infection with HCV genotype 3.In these data, the association between severe liver disease and HIV was underestimated, if given the observed data the chance of observing HIV status is high when this is positive. Inference for two other risk factors were robust to plausible local departures from the MAR assumption.We have demonstrated the practical utility of, and advocate, a pragmatic widely applicable approach to exploring plausible departures from the MAR assumption post multiple imputation. We have developed guidelines for applying this approach to epidemiological studies.
Paola Mancino,Katia Falasca,Claudio Ucciferri,Eligio Pizzigallo
Mediterranean Journal of Hematology and Infectious Diseases , 2010, DOI: 10.4084/mjhid.2011.
Abstract: Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR). To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection.
Discovery of Cellular Proteins Required for the Early Steps of HCV Infection Using Integrative Genomics  [PDF]
Ji Hoon Park, Solip Park, Jae-Seong Yang, Oh Sung Kwon, Sanguk Kim, Sung Key Jang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0060333
Abstract: Successful viral infection requires intimate communication between virus and host cell, a process that absolutely requires various host proteins. However, current efforts to discover novel host proteins as therapeutic targets for viral infection are difficult. Here, we developed an integrative-genomics approach to predict human genes involved in the early steps of hepatitis C virus (HCV) infection. By integrating HCV and human protein associations, co-expression data, and tight junction-tetraspanin web specific networks, we identified host proteins required for the early steps in HCV infection. Moreover, we validated the roles of newly identified proteins in HCV infection by knocking down their expression using small interfering RNAs. Specifically, a novel host factor CD63 was shown to directly interact with HCV E2 protein. We further demonstrated that an antibody against CD63 blocked HCV infection, indicating that CD63 may serve as a new therapeutic target for HCV-related diseases. The candidate gene list provides a source for identification of new therapeutic targets.
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