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https://www.readbyqxmd.com/read/27925362/ns5a-inhibitors-for-the-treatment-of-hepatitis-c-infection
#1
Stefano Gitto, Nesrine Gamal, Pietro Andreone
Today, we are witnessing a new era for the treatment of hepatitis C with excellent rates of virologic response and very good safety profiles. Among the many classes of direct acting antivirals, the inhibitors of non-structural protein 5A are particularly interesting. NS5A is phosphorylated protein with a relevant role in viral replication. HCV-NS5A inhibitors show high potency, very good safety profile and high barrier to resistance. The amazing in vitro effectiveness of this class is associated with great efficacy in clinical trials in combination protocols with antivirals of other classes, with sustained virological response (SVR) obtained in more than 90% of patients...
December 7, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27924186/treatment-of-chronic-hepatitis-c-infection-with-sofosbuvir-based-regimens-in-a-commercially-insured-patient-population
#2
John Barron, Yiqiong Xie, Sze-Jung Wu, Jeff White, Joseph Singer, Bernard Tulsi, Alan Rosenberg
BACKGROUND: The response to treatment with direct-acting antiviral agents in patients with chronic hepatitis C virus (HCV) is not well-characterized in the real-world setting. OBJECTIVE: To describe patients' response to 3 sofosbuvir-based treatment regimens among commercially insured patients with chronic HCV. METHODS: In this observational study, we identified patients with HCV who started sofosbuvir treatment with 1 of 3 sofosbuvir-based regimens between December 1, 2013, and April 30, 2014, in the HealthCore Integrated Research Database, a large managed care repository...
September 2016: American Health & Drug Benefits
https://www.readbyqxmd.com/read/27924080/global-epidemiology-and-burden-of-hcv-infection-and-hcv-related-disease
#3
REVIEW
Aaron P Thrift, Hashem B El-Serag, Fasiha Kanwal
Chronic HCV infection is a global health problem that affects >184 million people worldwide. HCV is associated with several hepatic and extrahepatic disorders, including several malignancies. The burden of HCV-related disorders is influenced by the number of new and existing cases, number of existing cases and the natural history of the infection. The natural history of HCV is affected by several demographic, virological, clinical and lifestyle factors. Major variations exist in the burden of HCV among different populations and geographical regions, as well as over time...
December 7, 2016: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27920481/new-real-time-pcr-method-to-identify-single-point-mutations-in-hepatitis-c-virus
#4
Qian Chen, Irene Belmonte, Maria Buti, Leonardo Nieto, Damir Garcia-Cehic, Josep Gregori, Celia Perales, Laura Ordeig, Meritxell Llorens, Maria Eugenia Soria, Rafael Esteban, Juan Ignacio Esteban, Francisco Rodriguez-Frias, Josep Quer
AIM: To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus (HCV). METHODS: In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir...
November 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27918880/racial-differences-in-hiv-and-hcv-risk-behaviors-transmission-and-prevention-knowledge-among-non-treatment-seeking-individuals-with-opioid-use-disorder
#5
Verena E Metz, Maria A Sullivan, Jermaine D Jones, Elizabeth Evans, Rachel Luba, Jonathan Vogelman, Sandra D Comer
In light of New York's recently reinforced strategy to end the AIDS epidemic by expanding testing, treatment, and access to pre-exposure prophylaxis (PrEP), we assessed drug use and sexual risk behaviors, along with HIV/Hepatitis C virus (HCV) transmission and prevention knowledge among non-treatment-seeking adults with opioid use disorder (OUD) in New York City. Over the course of 18 months, volunteers screening for research studies in the Opioid Laboratory at the New York State Psychiatric Institute completed a locally developed self-assessment questionnaire...
December 5, 2016: Journal of Psychoactive Drugs
https://www.readbyqxmd.com/read/27917261/anti-hepatitis-c-virus-drugs-and-kidney
#6
REVIEW
Paul Carrier, Marie Essig, Marilyne Debette-Gratien, Denis Sautereau, Annick Rousseau, Pierre Marquet, Jérémie Jacques, Véronique Loustaud-Ratti
Hepatitis C virus (HCV) mainly targets the liver but can also induce extrahepatic manifestations. The kidney may be impacted via an immune mediated mechanism or a cytopathic effect. HCV patients are clearly at a greater risk of chronic kidney disease (CKD) than uninfected patients are, and the presence of CKD increases mortality. Interferon-based therapies and ribavirin are difficult to manage and are poorly effective in end-stage renal disease and hemodialysis. These patients should be given priority treatment with new direct anti-viral agents (DAAs) while avoiding peginterferon and ribavirin...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27917084/sofosbuvir-and-simeprevir-combination-therapy-for-hcv-genotype-1-infection-results-of-a-single-center-va-experience
#7
Seth N Sclair, Maria Del Pilar Hernandez, Evan Vance, Dani Gilinski, Helen Youtseff, Maribel Toro, Marie Antoine, Lennox J Jeffers, Adam Peyton
Treatment of chronic hepatitis C virus (HCV) infection remains a priority in the veterans affairs (VA) health care system nationwide, as there is a high burden of liver disease due to HCV infection among US veterans. The combination of sofosbuvir and simeprevir was the first all-oral antiviral regimen used in clinical practice to treat veterans with HCV infection. In this study, we report a single-center experience showing both the feasibility and effectiveness of this all-oral combination to treat HCV genotype 1 infection...
August 2016: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27916546/new-direct-acting-antivirals-for-patients-with-chronic-hcv-infection-can-we-monitor-treatment-using-an-hcv-core-antigen-assay
#8
R Alonso, F Pérez-García, D Ampuero, E Reigadas, E Bouza
We evaluated the diagnostic usefulness of an HCV core antigen (HCV-Ag) assay in HCV-infected patients undergoing treatment with direct-acting antivirals. We analyzed 103 samples from 28 patients. Compared with RT-PCR, sensitivity was 96.2% and specificity was 100%. The correlation between techniques was excellent (Pearson coefficient: 0.871). HCV-Ag proved to be useful in patients with sustained viral response and in patients who experienced treatment failures.
November 17, 2016: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/27914803/effectiveness-of-direct-acting-antivirals-in-hepatitis-c-virus-infection-in-haemodialysis-patients
#9
Soraya Abad, Almudena Vega, Diego Rincón, Eduardo Hernández, Evangelina Mérida, Nicolás Macías, Raquel Muñoz, Mónica Milla, Jose Luño, Juan Manuel López-Gómez
Hepatitis C virus (HCV) infection is highly prevalent among patients on haemodialysis and leads to a poorer prognosis compared to patients who do not have said infection. Treatment with interferon and ribavirin is poorly tolerated and there are limited data on the experience with new direct-acting antivirals (DAAs). The aim of this study is to retrospectively analyse the current prevalence of HCV infection and efficacy and safety results with different DAA regimens in the haemodialysis population of 2hospital areas...
November 30, 2016: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/27906834/successful-continuation-of-hcv-treatment-following-liver-transplantation
#10
Carlos Fernández Carrillo, Gonzalo Crespo, Juan de la Revilla, Lluís Castells, Maria Buti, José Luis Montero, Emilio Fábrega, Inmaculada Fernández, Cristina Serrano-Millán, Victoria Hernández, José Luis Calleja, María-Carlota Londoño
BACKGROUND: Guidelines recommend that patients with hepatitis C virus (HCV)-related liver disease be treated for HCV before liver transplant (LT) to eliminate the virus prior to surgery. However, the unpredictability of donor organ availability may limit treatment duration. Interruption of HCV treatment with resumption post-LT is one potential solution which has not been investigated widely. METHODS: Patients from 5 clinical centres included in the large, national, noninterventional Hepa-C registry who started treatment with direct-acting antiviral agents (DAAs) while awaiting LT were identified retrospectively and followed up prospectively...
December 1, 2016: Transplantation
https://www.readbyqxmd.com/read/27905669/secondary-prophylaxis-of-hepatocellular-carcinoma-the-comparison-of-direct-acting-antivirals-with-pegylated-interferon-and-untreated-cohort
#11
R Vukotic, R Di Donato, F Conti, A Scuteri, C Serra, P Andreone
During the past two decades, several studies showed reduced rates of hepatocellular carcinoma recurrence in patients with HCV-related cirrhosis after interferon-based antiviral therapies respect to untreated controls, even without reaching viral clearance. The recent development of new all-oral regimens with direct-acting antivirals has radically improved the therapeutic management of hepatitis C. Nevertheless, paradoxical, or at least unexpected, high rates of both occurrence and recurrence of hepatocellular carcinoma after a treatment with direct-acting antivirals, have been reported in the recent literature...
December 1, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27905175/racial-disparity-in-all-cause-mortality-among-hepatitis-c-virus-infected-individuals-in-a-general-us-population-nhanes-iii
#12
B Emmanuel, M D Shardell, L Tracy, S Kottilil, S S El-Kamary
There are few long-term nationally representative studies of all-cause mortality among those infected with hepatitis C virus (HCV). When an additional 5 years of data were made publicly available in 2015, the Third National Health and Nutrition Examination Survey Linked Mortality File became the longest nationally representative study in the United States. Our objective was to update the estimated HCV-associated all-cause mortality in the general US population and determine any differences by sex, age and race/ethnicity...
December 1, 2016: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/27903217/rational-drug-discovery-of-hcv-helicase-inhibitor-improved-docking-accuracy-with-multiple-seedings-of-autodock-vina-and-in-situ-minimization
#13
SeeKhai Lim, Rozana Othman, Rohana Yusof, ChoonHan Heh
BACKGROUND: Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximate 3% of the global populations. Despite the present of several direct antiviral agents in the treatment of hepatitis C, the standard treatment for HCV is accompanied by several drawbacks such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants. OBJECTIVES: To discover potential inhibitors for HCV helicase through an optimized in silico approach...
November 30, 2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27902932/adenosine-triphosphate-analogs-can-efficiently-inhibit-the-zika-virus-rna-dependent-rna-polymerase
#14
Kamil Hercík, Jaroslav Kozak, Michal Šála, Milan Dejmek, Hubert Hřebabecký, Eva Zborníková, Miroslav Smola, Daniel Ruzek, Radim Nencka, Evzen Boura
We describe the expression and purification of an active recombinant Zika virus RNA-dependent RNA polymerase (RdRp). Next, we present the development and optimization of an in vitro assay to measure its activity. We then applied the assay to selected triphosphate analogs and discovered that 2'-C-methylated nucleosides exhibit strong inhibitory activity. Surprisingly, also carbocyclic derivatives with the carbohydrate locked in a North-like conformation as well as a ribonucleotide with a South conformation exhibited strong activity...
November 27, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27902444/oncolytic-reovirus-as-a-combined-antiviral-and-anti-tumour-agent-for-the-treatment-of-liver-cancer
#15
Adel Samson, Matthew J Bentham, Karen Scott, Gerard Nuovo, Abigail Bloy, Elizabeth Appleton, Robert A Adair, Rajiv Dave, Adam Peckham-Cooper, Giles Toogood, Seishi Nagamori, Matthew Coffey, Richard Vile, Kevin Harrington, Peter Selby, Fiona Errington-Mais, Alan Melcher, Stephen Griffin
OBJECTIVE: Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. DESIGN AND RESULTS: Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication...
November 15, 2016: Gut
https://www.readbyqxmd.com/read/27890169/hepatitis-c-virus-infection-and-rheumatic-diseases-the-impact-of-direct-acting-antiviral-agents
#16
REVIEW
Patrice Cacoub, Cloé Commarmond, David Sadoun, Anne Claire Desbois
Chronic hepatitis C virus (HCV) infection is associated with liver and extrahepatic complications, including B-cell lymphoma, cardiovascular and kidney diseases, glucose metabolism impairment and rheumatic conditions ie, arthralgia, myalgia, cryoglobulinemia vasculitis, sicca syndrome and the production of autoantibodies. The treatment has long been based on interferon alpha (IFN) that was found poorly effective, and contraindicated in many autoimmune/inflammatory disorders because of possible exacerbation of rheumatic disorders...
February 2017: Rheumatic Diseases Clinics of North America
https://www.readbyqxmd.com/read/27888038/evidence-of-bottleneck-effect-on-hepatitis-c-virus-transmission-between-a-couple-under-interferon-based-therapy
#17
Rafael Alves da Silva, Isabel Maria Vicente Guedes de Carvalho, Renata Prandini Adum de Matos, Lilian Hiromi Tomonari Yamasaki, Cíntia Bittar, Paula Rahal, Ana Carolina Gomes Jardim
Issues on the correlation of viral genetic diversity and treatment response to the hepatitis C infection remain uncertain. The bottleneck effect dictates the characteristics of the viral population that will establish the infection in a new host and is related to how the immune system and treatment will be effective against the virus. Here we evaluated the phylogenetic characteristics of quasispecies population and the treatment response pattern of a HCV infected couple. We also analyzed whether the viral population of these patients indicated that they were exposed to the same source for primer infection...
November 22, 2016: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/27882839/real-world-drug-costs-of-treating-hepatitis-c-genotypes-1-4-with-direct-acting-antivirals-initiating-treatment-at-fibrosis-0-2-and-3-4
#18
Timothy A Bach, Kathy Zaiken
BACKGROUND: Direct-acting antivirals (DAA) for the treatment of hepatitis C virus (HCV) have drastically improved outcomes but are also very costly. For this reason, priority for treatment is often given to patients with a higher fibrosis score at baseline by payers and providers rather than treating all eligible patients. Simulation studies have suggested that waiting to treat patients until fibrosis 3-4 may be more costly and result in worse outcomes; however, real-world implications are unknown...
December 2016: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27882066/bioinformatic-analysis-of-codon-usage-and-phylogenetic-relationships-in-different-genotypes-of-the-hepatitis-c-virus
#19
Mojtaba Mortazavi, Mohammad Zarenezhad, Seyed Moayed Alavian, Saeed Gholamzadeh, Abdorrasoul Malekpour, Mohammad Ghorbani, Masoud Torkzadeh Mahani, Safa Lotfi, Ali Fakhrzad
BACKGROUND: The hepatitis C virus (HCV) has six major genotypes. The purpose of this study was to phylogenetically investigate the differences between the genotypes of HCV, and to determine the types of amino acid codon usage in the structure of the virus in order to discover new methods for treatment regimes. METHODS: The codon usage of the six genotypes of the HCV nucleotide sequence was investigated through the online application available on the website Gene Infinity...
October 2016: Hepatitis Monthly
https://www.readbyqxmd.com/read/27881614/performance-characteristics-of-a-new-consensus-commercial-kit-for-hepatitis-d-virus-rna-viral-load-quantification
#20
Frédéric Le Gal, Samira Dziri, Athenaïs Gerber, Chakib Alloui, Zahia Ben Abdesselam, Dominique Roulot, Ségolène Brichler, Emmanuel Gordien
Hepatitis Delta virus (HDV) is responsible for fulminant hepatitis and liver failure, and accelerates evolution towards cirrhosis and hepatocellular carcinoma in hepatitis B virus-infected patients. To date treatment relies upon long-term administration of pegylated alpha-interferon with sustained virological response in 30% of the patients. Very recently, new promising anti HDV therapies have been developed and are already used in clinical trials. HDV-RNA viral load (HDVL) monitoring must be an integral part of the management of the infected-patients...
November 23, 2016: Journal of Clinical Microbiology
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