1,720,974 research outputs found

    Prevention of mother-to-child transmission of hepatitis B virus and hepatitis C virus.

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    About 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Vertical transmission is the most important mechanism of infection persistence in endemic areas. About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). Mother-to-child transmission of HCV, which occurs in 3-10\% of cases, is the leading route of infection in childhood. This review focuses on strategies to reduce the vertical transmission of HBV and HCV. The at-birth prophylaxis of newborns of HBV-infected mothers with specific immunoglobulin and vaccine plus administration of antivirals (tenofovir or telbivudine) in the third trimester of pregnancy (in case of high maternal viral load) greatly reduces the risk of transmission. In contrast, currently there is no drug able to reduce the vertical transmission of HCV infection. We discuss the possibility of reducing mother-to-child HCV transmission using newly available antivirals or antivirals in the pipeline for the treatment of hepatitis C

    Is it possible to predict HCV-related liver cirrhosis non-invasively through routine laboratory parameters?

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    It is estimated that hepatitis C virus (HCV) infects chronically about 160 million people worldwide. Between 15 and 56\% of these chronic carriers will evolve towards liver cirrhosis during their lifetimes. In managing subjects with HCV chronic infection, it is crucial to perform accurate staging of the disease and specifically to ascertain whether or not they have liver cirrhosis for at least three reasons: 1) the presence of cirrhosis has prognostic relevance as it entails a relatively high risk of developing decompensation (e.g., ascites, encephalopathy, jaundice, oesophageal variceal bleeding) or evolution toward hepatocellular carcinoma (HCC); 2) the presence of liver cirrhosis is the main indication for urgent treatment and paradoxically a factor predicting a poor response to currently available therapies. The timing of therapy is particular important considering that the new era of interferon-free antivirals will be a reality in a few years; 3) finally, in the presence of liver cirrhosis current guidelines recommend periodical screening for the presence of oesophageal varices and HCC. With the exception of the most advanced stages, the diagnosis of liver cirrhosis is obtained by performing a percutaneous liver biopsy, which is an invasive technique and therefore is associated with a low but non-negligible rate of complications and even death. Finally, it has a non-null rate of false negative for the diagnosis of liver cirrhosis when compared with surgical biopsy. For these reasons several authors have devised non-invasive scores to predict cirrhosis using different means. The most useful are based on liver stiffness (fibroscan), on a panel of blood tests and a proprietary algorithm (fibrotest) or on routinely available parameters. This review focuses on the different scores based on routine parameters that differ in their ease of calculation, in their diagnostic power and in the information provided. Further studies are required to compare the diagnostic performance of different non-invasive scores with the histologic evaluation and other non-invasive methods (fibroscan or fibrotest) on independent cohorts of patients

    Interferon-free therapies for chronic hepatitis C: toward a hepatitis C virus-free world?

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    About 2\% of the world's population is estimated to be chronically infected with hepatitis C virus (HCV). These chronic carriers are at risk of developing liver cirrhosis and its complications. Successful treatment of HCV infection is associated with improved quality of life and increased survival. Antiviral approaches were formerly based on interferon and therefore all patients with a contraindication to interferon were excluded from treatment (e.g., patients with decompensated disease, severe impairment of other organs). Very recently, interferon-free combinations have become available for genotypes 2 and 3. This review focuses on the most recently reported data on the various interferon-free combinations used (namely, sofosbuvir-based combinations, the ABT-450/ombitasvir/dasabuvir/ribavirin combination, the daclatasvir/asunaprevir combination, and the MK-5172/MK-8742 combination). All these combinations yielded amazing results in terms of efficacy (90-100\%), tolerability and safety. If the problem of the high cost is overcome, interferon-free therapies will lead to what has long been a chimera, namely, an HCV-free world

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Investigational nucleoside and nucleotide polymerase inhibitors and their use in treating hepatitis C virus

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    Introduction: About 150 million people worldwide are estimated to be chronically infected with the hepatitis C virus (HCV). Successful antiviral treatment can stop the progression of the disease toward liver cirrhosis, hepatocellular carcinoma and death. IFN has been the drug of choice and the backbone of all combinations in the past two decades. However, an IFN-free combination (sofosbuvir and ribavirin) has been recently approved for genotypes 2 and 3 patients with many other drugs in preclinical and clinical development.Areas covered: This review focuses on investigational nucleoside or nucleotide inhibitors of viral polymerase that are potential treatments of HCV. The article reviews drugs that are currently under investigational status.Expert opinion: Currently, mericitabine has the most robust data but its efficacy appears to be less than optimal. Other drugs such as ALS-2200 (and its diastereomer VX-135) and BMS-986094 are promising but the data in humans are too scanty to draw conclusions about their future role at this current point in time. Other promising molecules are LG-7501, ACH-3422 and EP-NI266, although no clinical studies have been performed thus far, so this must be rectified. Another drug of promise GS-6620 has displayed a high degree of pharmacokinetic and pharmacodynamic variability, which makes further development unlikely

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    ABT-450: A novel protease inhibitor for the treatment of hepatitis C virus infection

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    About 2.3% of the world's population is infected with hepatitis C virus (HCV) and patients have a high risk of developing liver cirrhosis and its complications. Current therapeutic strategies are based on a combination of pegylatedinterferon, ribavirin and (only for patients with genotype 1 infection) a protease inhibitor (boceprevir or telaprevir). Consequently, all these combinations have the limitations of interferon. In fact, they are contraindicated in decompensated disease and in subjects with severe comorbidities, and are associated with a high rate of side effects. Moreover, they are poorly effective in advanced disease. As complete viral eradication is associated with improved disease-free survival, several molecules are under clinical development for their potential to overcome the drawbacks of currently available treatments. This review focuses on the pharmacodynamics, pharmacokinetics, safety and tolerability of ABT-450, a potent inhibitor of non-structural 3 protease. ABT-450 is a substrate of cytochrome P450; hence its co-administration with ritonavir, a cytochrome P450 inhibitor, dramatically increases the plasma concentration and half-life of ABT-450 and allows once-daily administration. Given in monotherapy for 3 days at different doses, ABT-450 causes a mean maximum viral decline of about 4 logs. Interestingly, high doses of ABT-450 are associated with a reduced and delayed development of resistance-conferring mutations. Given in combination with other direct antiviral drugs, the sustained response rate reaches 90-95% in both naive and treatment-experienced genotype 1 patients, and tolerability is good. In conclusion, ABT-450 is an excellent component of interferon-free combinations for the treatment of chronic HCV infection

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Efficacy and Safety of Sofosbuvir in Treatment of Chronic Hepatitis C: The Dawn of the a New Era.

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    Hepatitis C virus (HCV) infection affects about 160 million people worldwide. Currently, it is treated with pegylated interferon (PEG-IFN) plus ribavirin, associated with a protease inhibitor in case of genotype 1 infection. However, this combination is often contraindicated and associated with severe adverse events that limit its use in clinical practice. Several drugs active against HCV are in an advanced phase of clinical development. Among these, sofosbuvir appears one of the most promising candidates for use in association with both interferon and interferon-free combinations. This review focuses on the results of several sofosbuvir-based phase III trials that have very recently become available. These studies show the administration of sofosbuvir associated with PEG-IFN and ribavirin for 12 weeks is associated with a very high rate of sustained virological responses (SVR) (about 90\%) in naïve patients with genotypes 1, 4, 5 or 6. In patients infected by genotypes 2 or 3, the interferon-free combination of sofosbuvir and ribavirin administered for 12 weeks is associated with a SVR of 97\% and 56\% in naïve patients, and of 86\% and 30\% in experienced genotype 2 or 3 patients, respectively. The safety and tolerability profile is optimal and consistent with that of the other drugs administered in the combination (ribavirin and/or interferon). In conclusion, the recent phase III trials of sofosbuvir confirm the excellent results of phase II studies in terms of efficacy and safety and will probably open a new era in the fight against HCV
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