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A Novel Promising Therapeutic Option Against HCV... [Curr Med Chem. 2013] - PubMed - NCBI

PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Hepatitis C New Drugs Review
FDA approved Incivek(telaprevir, Vertex) on Monday 23 May by its PDUFA deadline.A paradigm shift in the treatment of Hepatitis C virus infection. http://knol.google.com/k/krishan-maggon/boceprevir-merck-telaprevir-vertex/3fy5eowy8suq3/151#
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Created public version #121 of the knol: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval"

Created public version #121 of the knol: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval" | Hepatitis C New Drugs Review | Scoop.it
Krishan Maggon published version 121 of a knol titled: "Boceprevir (Merck) & Telaprevir (Vertex) Hepatitis C : FDA Review & Approval"...
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Costs of Telaprevir-based Triple Therapy for Hepatitis C: $189,000 per Sustained Virologic Response - Bichoupan - Hepatology - Wiley Online Library

Costs of Telaprevir-based Triple Therapy for Hepatitis C: $189,000 per Sustained Virologic Response - Bichoupan - Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it
Costs of Telaprevir based Triple Therapy for Hepatitis C: $189,000 per Sustained Virologic Response. Hepatology http://t.co/OtkBXgxpO0
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There have been lot of media headlines abour the Gilead $1000/pill drug Sovaldi (sofosbuvir) but the actual cost of existing HCV therapy may be even higher with much lower cure rates?

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Studies reveal success of new oral drug regimens for hepatitis C - Medical News Today

Studies reveal success of new oral drug regimens for hepatitis C - Medical News Today | Hepatitis C New Drugs Review | Scoop.it
Medical News Today Studies reveal success of new oral drug regimens for hepatitis C Medical News Today "The efficacy and safety of 24 weeks of daclatasvir plus asunaprevir represents a huge improvement on the first generation of protease...
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The three new clinical studies published in Lancet were scooped previously and have been covered in large number of media articles as today is World Hepatitis Day to highlight the impact and economic cost of the disease. 

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All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort study : The Lancet

SummaryBackgroundAn unmet need exists for interferon-free and ribavirin-free treatments for chronic hepatitis C virus (HCV) infection. In this study, we assessed all-oral therapy with daclatasvir (NS5A replication complex inhibitor) plus asunaprevir (NS3 protease inhibitor) in patients with genotype 1b infection, including those with high unmet needs or cirrhosis, or both.MethodsWe did this phase 3, multicohort study (HALLMARK-DUAL) at 116 sites in 18 countries between May 11, 2012, and Oct 9, 2013. Patients were adults with chronic HCV genotype 1b infection who were treatment-naive; previous non-responders to peginterferon alfa plus ribavirin; or medically ineligible for, previously intolerant of, or ineligible for and intolerant of peginterferon alfa plus ribavirin. Treatment-naive patients were randomly assigned (2:1 ratio) by an interactive voice-response system with a computer-generated random allocation sequence (stratified by cirrhosis status) to receive daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily or placebo for 12 weeks. Patients and investigator sites were masked to treatment assignment and HCV RNA results to the end of week 12. The treatment-naive group assigned to daclatasvir plus asunaprevir continued open-label treatment to the end of week 24; participants assigned to placebo entered another daclatasvir plus asunaprevir study. Non-responders and ineligible, intolerant, or ineligible and intolerant patients received open-label daclatasvir plus asunaprevir for 24 weeks. The primary endpoint was sustained virological response at post-treatment week 12. Efficacy analyses were restricted to patients given daclatasvir plus asunaprevir. This trial is registered with ClinicalTrials.gov, number NCT01581203.FindingsThis study included 307 treatment-naive patients (205 received daclatasvir plus asunaprevir and 102 received placebo; all randomly assigned patients received the intended treatment), 205 non-responders, and 235 ineligible, intolerant, or ineligible and intolerant patients. Daclatasvir plus asunaprevir provided sustained virological response in 182 (90%, 95% CI 85—94) patients in the treatment-naive cohort, 168 (82%, 77—87) in the non-responder cohort, and 192 (82%, 77—87) in the ineligible, intolerant, or ineligible and intolerant cohort. Serious adverse events occurred in 12 (6%) patients in the treatment-naive group; 11 (5%) non-responders, and 16 (7%) ineligible, intolerant, or ineligible and intolerant patients; adverse events leading to discontinuation (most commonly reversible increases in alanine or aspartate aminotransferase) occurred in six (3%), two (1%), and two (1%) patients, respectively, with no deaths recorded. Grade 3 or 4 laboratory abnormalities were uncommon, with low incidences of aminotransferase increases during the first 12 weeks with daclatasvir plus asunaprevir and placebo in treatment-naive patients (≤2% each).InterpretationDaclatasvir plus asunaprevir provided high sustained virological response rates in treatment-naive, non-responder, and ineligible, intolerant, or ineligible and intolerant patients, and was well tolerated in patients with HCV genotype 1b infection. These results support the use of daclatasvir plus asunaprevir as an all-oral, interferon-free and ribavirin-free treatment option for patients with HCV genotype 1b infection, including those with cirrhosis.
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The Lancet, Early Online Publication, 28 July 2014doi:10.1016/S0140-6736(14)61059-XCite or Link Using DOI Copyright © 2014 Elsevier Ltd All rights reserved.All-oral daclatasvir plus asunaprevir for hepatitis C virus genotype 1b: a multinational, phase 3, multicohort studyProf Michael Manns MD a b , Prof Stanislas Pol MD c, Prof Ira M Jacobson MD d, Prof Patrick Marcellin MD e, Prof Stuart C Gordon MD f, Cheng-Yuan Peng MD g, Prof Ting-Tsung Chang MD h, Prof Gregory T Everson MD i, Prof Jeong Heo MD j, Prof Guido Gerken MD k, Prof Boris Yoffe MD l, William J Towner MD m, Marc Bourliere MD n, Sophie Metivier MD o, Chi-Jen Chu MD p, ProfWilliam Sievert MD q, Prof Jean-Pierre Bronowicki MD r, Prof Dominique Thabut MD s, Prof Youn-Jae Lee MD t, Prof Jia-Horng KaoMD u, Fiona McPhee PhD v, Justin Kopit PhD v, Patricia Mendez MD w, Misti Linaberry MPH w, Eric Hughes MD w, Stephanie Noviello MD w, on behalf of the HALLMARK-DUAL Study Team
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Assessing the Long-Term Value of Hepatitis C Treatments | PhRMA

Assessing the Long-Term Value of Hepatitis C Treatments | PhRMA | Hepatitis C New Drugs Review | Scoop.it
The current debate regarding the cost of new and forthcoming hepatitis C treatments has brought to light a long-standing discussion about the cost and value of innovative new medicines.
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http://www.cnn.com/2014/07/24/opinion/castellani-hepatitis-drugs/index.html

 

Hepatitis drugs save money in long run

PricewaterhouseCoopers estimates that new medicines for hepatitis C will increase health care costs by just half a percent in 2014 and will level off after 2016 as patients are cured. This is particularly noteworthy given that public discussions have focused almost exclusively on the price of new medicines while ignoring the tremendous societal benefits…” “Although critics say the price of a promising new hepatitis C drug raises the cost of insurance, research from Milliman in 2009 projected that, without a cure for hepatitis C, annual U.S. medical costs associated with the disease will nearly triple over 20 years -- from $30 billion to $85 billion -- indicating that curing the disease can help reduce future medical costs.” “…Simple economics will remind us that, while investments at first may seem challenging, the prescription drug life cycle, market forces and tenacious global competition can lead to lower prices and broad access over time.” - See more at: http://www.phrma.org/catalyst/assessing-the-longterm-value-of-hepatitis-c-treatments?utm_source=PhRMA+e-news&utm_campaign=e5b2c0ab76-Update_from_PhRMA_07_26_2014&utm_medium=email&utm_term=0_4a09d8e2e7-e5b2c0ab76-51458761&ct=t(Update_from_PhRMA_07_26_2014)#sthash.rPhMcCCl.dpuf

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Safety of direct-acting antivirals in the treatment of chronic hepatitis C, Expert Opinion on Drug Safety, Informa Healthcare

Safety of direct-acting antivirals in the treatment of chronic hepatitis C, Expert Opinion on Drug Safety, Informa Healthcare | Hepatitis C New Drugs Review | Scoop.it
How cost effective are protease inhibitors for hepatitisC? #Boceprevir #Telaprevir find out for FREE http://t.co/FJubvevOE5 #ThinkHepatitis

 

Introduction: Combination therapy with pegylated interferon, ribavirin and the two first-generation NS3/4A protease inhibitors (PIs), telaprevir (TVR) and boceprevir (BOC), is the new standard-of-care therapy for patients who are chronically infected with genotype 1 hepatitis C virus. These combinations significantly increase sustained virological response (SVR) rates, but they also increase the rates of adverse events (AEs). Appearance of significant AEs may necessitate dose reduction or discontinuation of treatment, and may impact on virological response.

Areas covered: In registration trials, IFN-related AEs were a dominant feature in both types of therapy. Some events were more frequent with PI-containing regimens, like anemia and dysgeusia with BOC and anemia, pruritus, rash and anorectal symptoms with TVR. This review addresses the early identification and management of AEs to improve tolerance, and to avoid reduction in SVR rates.

Expert opinion: Every patient will experience adverse effects to differing degrees; a systematic approach to their management can be very helpful. Early recognition and intervention can help clinicians ensure that patients are able to complete therapy where possible and achieve the goal of viral eradication. Treatment with the next generation of antivirals will improve safety and efficacy.

Keywords: adverse events, boceprevir, direct-acting antivirals, hepatitis C virus, pegylated interferon, ribavirin, safety, telaprevir 




Read More: http://informahealthcare.com/stoken/default+domain/HepRev/full/10.1517/14740338.2014.884068

Krishan Maggon 's insight:

Great review concerning ADR of HCV antiviral drugs.

 

Open access full text

 

Reviews

Safety of direct-acting antivirals in the treatment of chronic hepatitis C

 

March 2014, Vol. 13, No. 3 , Pages 307-319 (doi:10.1517/14740338.2014.884068)PDF (308 KB)PDF Plus (337 KB)ReprintsPermissionsEzequiel Ridruejo 1,2 MD1 Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno “CEMIC”, Department of Medicine, Hepatology Section, Avda. Las Heras 2939, (C1425ASG) Ciudad Autónoma de Buenos Aires, Argentina +54 11 5299 1221; +54 11 5299 0600 ext 5900;eridruejo@gmail.com2 Hospital Universitario Austral, Hepatology and Liver Transplant Unit, Pilar, Argentina




Read More: http://informahealthcare.com/stoken/default+domain/HepRev/full/10.1517/14740338.2014.884068

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Asunaprevir, a protease inhibitor for the treatment of hepatitis C inf

Peer reviewed article authored by (Gentile I, Buonomo AR, Zappulo E, Minei G, Morisco F, Borrelli F, Coppola N, Borgia G). Read article or submit your manuscript for publishing.
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Could Gilead's Sovaldi also treat Hep C in HIV patients?

Could Gilead's Sovaldi also treat Hep C in HIV patients? | Hepatitis C New Drugs Review | Scoop.it
The results of a new clinical trial were excellent news for Gilead, but women and patients with cirrhosis were underrepresented in the study. (.@GileadSciences' #Sovaldi is already the talk of the town.
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The original study was covered in previous scoop.

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Antiviral treatment of hepatitis C

Antiviral treatment of hepatitis C | Hepatitis C New Drugs Review | Scoop.it

Abstract

Hepatitis C virus (HCV) infection is a substantial health problem worldwide. Most patients infected with HCV remain chronically infected, with an increased risk of cirrhosis and hepatocellular carcinoma. Although they are associated with toxicities and low sustained viral response rates, interferon alfa and ribavirin have been the mainstay of treatment until recently. New direct acting antivirals, specifically designed to inhibit three viral proteins (the NS3/4A protease, the NS5A protein, and the NS5B RNA dependent RNA polymerase) are now becoming available. The NS3/4A inhibitor simeprevir and NS5B inhibitor sofosbuvir have recently been licensed and can reduce the length of antiviral treatment, improve response rates, and allow for interferon-free regimens for some HCV genotypes. Several other newer direct acting antivirals have shown promise in clinical studies and are likely to be licensed soon. These agents seem to facilitate the use of shortened courses of combination interferon-free therapy, which are associated with high (>95%) sustained response rates and relatively few toxicities. These regimens have also been successful in patients who were previously difficult to treat, including those with cirrhosis, HIV coinfection, and those who have undergone liver transplantation. The high cost of these agents may be the biggest challenge to their implementation worldwide.

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State of the Art Review

 

Antiviral treatment of hepatitis C

 

BMJ 2014; 349 doi:

http://dx.doi.org/10.1136/bmj.g3308 
(Published 07 July 2014)
Cite this as: BMJ 2014;349:g3308

 Eoin R Feeney, clinical research fellow1, Raymond T Chung, director of Hepatology and Liver Center2Author affiliationsCorrespondence to: R T Chung RTCHUNG@partners.org

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Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment web resource - Smith - 2013 - Hepatology - Wiley Online Library

Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment web resource - Smith - 2013 - Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it
Abstract

The 2005 consensus proposal for the classification of hepatitis C virus (HCV) presented an agreed and uniform nomenclature for HCV variants and the criteria for their assignment into genotypes and subtypes. Since its publication, the available dataset of HCV sequences has vastly expanded through advancement in nucleotide sequencing technologies and an increasing focus on the role of HCV genetic variation in disease and treatment outcomes. The current study represents a major update to the previous consensus HCV classification, incorporating additional sequence information derived from over 1,300 (near-)complete genome sequences of HCV available on public databases in May 2013. Analysis resolved several nomenclature conflicts between genotype designations and using consensus criteria created a classification of HCV into seven confirmed genotypes and 67 subtypes. There are 21 additional complete coding region sequences of unassigned subtype. The study additionally describes the development of a Web resource hosted by the International Committee for Taxonomy of Viruses (ICTV) that maintains and regularly updates tables of reference isolates, accession numbers, and annotated alignments (http://talk.ictvonline.org/links/hcv/hcv-classification.htm). The Flaviviridae Study Group urges those who need to check or propose new genotypes or subtypes of HCV to contact the Study Group in advance of publication to avoid nomenclature conflicts appearing in the literature. While the criteria for assigning genotypes and subtypes remain unchanged from previous consensus proposals, changes are proposed in the assignment of provisional subtypes, subtype numbering beyond “w,” and the nomenclature of intergenotypic recombinant. Conclusion: This study represents an important reference point for the consensus classification of HCV variants that will be of value to researchers working in clinical and basic science fields. (Hepatology 2014;59:318-327)

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Increasing number of HCV genotypes makes it more complex for drug targeting. 

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1 Drug More Important to Gilead Than Sovaldi - Motley Fool

1 Drug More Important to Gilead Than Sovaldi - Motley Fool | Hepatitis C New Drugs Review | Scoop.it
1 Drug More Important to Gilead Than Sovaldi
Motley Fool
AbbVie is awaiting approval for a three-drug combination therapy that effectively cured 99% of genotype 1b patients during phase 3 trials.
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How Gilead Sciences Can Deliver A Double

How Gilead Sciences Can Deliver A Double | Hepatitis C New Drugs Review | Scoop.it
Gilead Sciences’ (NASDAQ:GILD) drug portfolio has 16 medications, and generates gross margins over 70% with net margins consistently over 30%. It’s newest drug, Sovaldi, is dramatically boosting revenues and earnings, and two of our Masters, Eugene Groysman and Mike Koza, have noticed. This week I talked to Eugene to find out why he thinks GILD, which is up 49% in the last year, can double from here. Eugene has a 12-year track record with Marketocracy with his average annual return of 18.3%. You can view Eugene‘s top five holdings, learn more about his strategy, and track his progress with monthly Performance Insights emailed directly to you at the end of each month by visiting our website.

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Marco Antonio Gonzalez's curator insight, July 11, 11:30 AM

About Gilead (parte one)

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Beyond sofosbuvir: What opportunity exists for a better nucleoside/nucleotide to treat hepatitis C?

Highlights

 

Sofosbuvir is a potent uridine nucleotide prodrug approved for genotype 1, 2, 3 and 4 hepatitis C patients.

Sofosbuvir shows some differential genotype efficacy, particularly in genotype 3.

Patients with severe renal impairment or taking drugs that induce P-glycoprotein may be contraindicated.

New nucleos(t)ide polymerase inhibitors should enable shorter treatment and an orthogonal resistance profile.

Recent clinical entrants appear similar to sofosbuvir and therefore may not provide added patient benefit.

Krishan Maggon 's insight:
Antiviral Research

Volume 107, July 2014, Pages 119–124

 

Beyond sofosbuvir: What opportunity exists for a better nucleoside/nucleotide to treat hepatitis C?Michael J. Sofia  Show more DOI: 10.1016/j.antiviral.2014.04.008
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Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Coinfection

Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Coinfection | Hepatitis C New Drugs Review | Scoop.it

Importance  Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon.

Objective  To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment.

Design, Setting, and Participants  Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants.

Interventions  Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks.

Main Outcomes and Measures  The primary study outcome was the proportion of patients with SVR (serum HCV <25 copies/mL) 12 weeks (SVR12) after cessation of HCV therapy.

Results  Among treatment-naive participants, 87 patients (76%) of 114 (95% CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95% CI, 70%-985), and 28 patients (67%) of 42 with genotype 3 (95% CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95% CI, 73%-99%) and 16 patients (94%) of 17 (95% CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed.

Conclusions and Relevance  In this open-label, nonrandomized, uncontrolled study, patients with HIV who were coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of SVR12. Further studies of this oral regimen in diverse populations of coinfected patients are warranted.

Trial Registration  clinicaltrials.gov Identifier: NCT01667731.

Krishan Maggon 's insight:

open access full text

 

Sofosbuvir and Ribavirin for Hepatitis C in Patients With HIV Coinfection FREEMark S. Sulkowski, MD1; Susanna Naggie, MD2; Jacob Lalezari, MD3; Walford Jeffrey Fessel, MD4; Karam Mounzer, MD5; Margaret Shuhart, MD6; Anne F. Luetkemeyer, MD7; David Asmuth, MD8; Anuj Gaggar, MD, PhD9; Liyun Ni, PhD9; Evguenia Svarovskaia, PhD9; Diana M. Brainard, MD9; William T. Symonds, PharmD9; G. Mani Subramanian, MD, PhD9; John G. McHutchison, MD9; Maribel Rodriguez-Torres, MD10; Douglas Dieterich, MD11 ; for the PHOTON-1 Investigators[+] Author AffiliationsJAMA. 2014;312(4):353-361. doi:10.1001/jama.2014.7734.
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World Hepatitis Day

World Hepatitis Day | Hepatitis C New Drugs Review | Scoop.it
Viral hepatitis kills 1.5 million people worldwide each year. That's as many people as HIV / AIDS. #thinkhepatitis

 

FOR THE WORLD'S 8TH BIGGEST KILLER, VIRAL HEPATITIS IS REMARKABLY NEGLECTED. 

That's why in 2010 the World Health Organization made World Hepatitis Day one of only 4 official disease-specific world health days, to be celebrated each year on the 28th July.

Millions of people across the world now take part in World Hepatitis Day, to raise awareness about viral hepatitis, and to call for access to treatment, better prevention programs and governments action.

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World Hepatitis Day: 28 July

 

Video Link

 

http://www.worldhepatitisalliance.org/en/helping-hands-official-whd-video.html

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Hepatitis E virus in blood components: a prevalence and transmission study in southeast England : The Lancet

Hepatitis E virus in blood components: a prevalence and transmission study in southeast England : The Lancet | Hepatitis C New Drugs Review | Scoop.it
Our findings suggest that HEV genotype 3 infections are widespread in the English population and in blood donors. Transfusion-transmitted infections rarely caused acute morbidity, but in some immunosuppressed patients became persistent. Although at present blood donations are not screened, an agreed policy is needed for the identification of patients with persistent HEV infection, irrespective of origin, so that they can be offered antiviral therapy.FundingPublic Health England and National Health Service Blood and Transplant.
Krishan Maggon 's insight:
The Lancet, Early Online Publication, 28 July 2014doi:10.1016/S0140-6736(14)61034-5Cite or Link Using DOI Copyright © 2014 Hewitt et al. Open Access article distributed under the terms of CC BY-NC-ND Published by Elsevier Ltd. All rights reserved.Hepatitis E virus in blood components: a prevalence and transmission study in southeast EnglandPatricia E Hewitt FRCPath a, Samreen Ijaz PhD b, Su R Brailsford PhD a c, Rachel Brett BSc a, Steven Dicks MSc a b, Becky Haywood BSc b, Iain T R Kennedy MFPH c, Alan Kitchen PhD a, Poorvi Patel MSc a b, John Poh PhD b, Katherine Russell MFPH c,Kate I Tettmar MBA a b, Joanne Tossell RN a, Ines Ushiro-Lumb FRCPath a b, Prof Richard S Tedder FRCPath a b d 
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Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patie...

SummaryBackgroundInterferon-free regimens are needed to treat hepatitis C virus (HCV) infections. We investigated the efficacy of combined simeprevir and sofosbuvir.MethodsWe enrolled patients with chronic HCV genotype 1 infections who had previously not responded to pegylated interferon (peginterferon) and ribavirin or were treatment naive. Patients were randomly assigned in a 2:2:1:1 ratio to receive 150 mg simeprevir and 400 mg sofosbuvir daily for 24 weeks with (group 1) or without (group 2) ribavirin or for 12 weeks with (group 3) or without (group 4) ribavirin, in two cohorts: previous non-responders with METAVIR scores F0—F2 (cohort 1) and previous non-responders and treatment-naive patients with METAVIR scores F3—F4 (cohort 2). The primary endpoint was sustained virological response 12 weeks after stopping treatment (SVR12). Analysis was done by intention to treat. Safety data from cohorts 1 and 2 were pooled for analysis. This study is registered with ClinicalTrials.gov, number NCT01466790.Findings168 patients were enrolled and randomised, and 167 started treatment (n=80 in cohort 1 and n=87 in cohort 2). SVR12 was achieved in 154 (92%) patients (n=72 [90%, 95% CI 81—96] in cohort 1 and n=82 [94%, 87—98] in cohort 2). The most common adverse events in the pooled groups were fatigue (n=52 [31%]), headache (n=33 [20%]), and nausea (n=26 [16%]). Grade 4 adverse events were seen in one (2%) of 54 patients in each of groups 1 and 3 and in three (10%) of 31 patients in group 2, whereas grade 3—4 events were reported in less than 5% of all patients, except increased blood amylase concentration. Serious adverse events were seen in four (2%) patients, all in groups 1 and 2. Four (2%) patients discontinued all study treatment because of adverse events, three before week 12.InterpretationCombined simeprevir and sofosbuvir was efficacious and well tolerated.
Krishan Maggon 's insight:
The Lancet, Early Online Publication, 28 July 2014doi:10.1016/S0140-6736(14)61036-9Cite or Link Using DOI Copyright © 2014 Elsevier Ltd All rights reserved.Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised studyProf Eric Lawitz MD a , Prof Mark S Sulkowski MD b, Reem Ghalib MD c, Maribel Rodriguez-Torres MD d, Prof Zobair M Younossi MD e, Ana Corregidor MD f, Edwin DeJesus MD g, Prof Brian Pearlman MD h, Prof Mordechai Rabinovitz MD i, Norman Gitlin MD j, Joseph K Lim MD k, Paul J Pockros MD l, John D Scott MD m, Bart Fevery MSc n, Tom Lambrecht MSc o, Sivi Ouwerkerk-Mahadevan PhD n, Katleen Callewaert MSc n, William T Symonds PharmD p, Gaston Picchio PhD q, Karen L Lindsay MDq, Maria Beumont MD n, Prof Ira M Jacobson MD r
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Politicizing Gilead's Research And Development Costs For Sovaldi Is A Reckless And Dangerous Misadventure

Politicizing Gilead's Research And Development Costs For Sovaldi Is A Reckless And Dangerous Misadventure | Hepatitis C New Drugs Review | Scoop.it
Gilead has become the whipping boy du jour for the forthcoming Obamacare-driven cost explosion in health spending. Politicians and the health-insurance industry have embarked on a high-profile campaign to shame Gilead for the price of its new wonder-drug, Sovaldi. If successful, this campaign will have terrible long-term consequences for medical innovation.

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Marco Antonio Gonzalez's curator insight, July 26, 1:06 AM

Interesting article in Forbe. About Gilead and Sovaldi

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Sovaldi (sofosbuvir, Gilead) to overtake Humira as the best selling human medicinal brand in 2014

Sovaldi (sofosbuvir, Gilead) to overtake Humira as the best selling human medicinal brand in 2014 | Hepatitis C New Drugs Review | Scoop.it

Gilead 2Q 2014 earnings press release., Sovaldi sales helped 2Q earnings increase to $ 6.4 billion in 2014 from $ 2.66 billion in 2Q2013, the increase coming from sofosbuvir sales.

 

Krishan Maggon 's insight:

With sales of $ 5.7 billion in the first half of 2014, Gilead hepatitis C drug is likely to emerge as the successor to Lipitor, unless government pressure forces company to reduce the price of 1000 dollar/pill. Projected sales in 2014 may reach $15 billion making it the best selling human medicine of all time.

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New Expensive Treatments for Hepatitis C Infection

Opinion from JAMA — New Expensive Treatments for Hepatitis C Infection (@Jama_current: The simple math is that #Sovaldi will add ~$300 to every insured person's premiums per yr over 5 yrs http://t.co/A4FLjYg9Sh)...
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The past, present and future of neutralizing antibodies for hepatitis C virus

The past, present and future of neutralizing antibodies for hepatitis C virus | Hepatitis C New Drugs Review | Scoop.it
Highlights

 

Recent studies have provided insight into the protective role of neutralizing antibodies in hepatitis C.

Neutralizing antibodies show broad reactivity for diverse HCV genotypes.

Recombinant HCV glycoproteins can elicit neutralizing antibodies.

The HCV E2 core structure can inform rational design of immunogens.

 

 

Krishan Maggon 's insight:
Antiviral Research

Volume 105, May 2014, Pages 100–111

Review The past, present and future of neutralizing antibodies for hepatitis C virusJonathan K. Balla, Alexander W. Tarra, Jane A. McKeatingb, ,  Show more DOI: 10.1016/j.antiviral.2014.02.013Open Access funded by Medical Research Council 
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Next-generation sequencing reveals large connected networks of intra-host HCV variants

Next-generation sequencing reveals large connected networks of intra-host HCV variants | Hepatitis C New Drugs Review | Scoop.it
Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host.

 

Conclusions

Most intra-host variants are organized into distinct single-mutation components that are: well separated from each other, represent genetic distances between viral variants, robust to sampling, reproducible and likely seeded during transmission events. Facilitated by NGS, large components offer a novel evolutionary framework for genetic analysis of intra-host viral populations and understanding transmission, immune escape and drug resistance.

 


Via Mel Melendrez-Vallard
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open access full text

 

Research

Next-generation sequencing reveals large connected networks of intra-host HCV variants

David S Campo1*, Zoya Dimitrova1, Lilian Yamasaki2, Pavel Skums1, Daryl TY Lau3,Gilberto Vaughan1, Joseph C Forbi1, Chong-Gee Teo1 and Yury Khudyakov1

*Corresponding author: David S Campo fyv6@cdc.gov

Author Affiliations

1Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

2Laboratory of Genomic Studies, Department of Biology, UNESP - São Paulo State University, Brazil

3Liver Center, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Massachusetts, USA

For all author emails, please log on.

BMC Genomics 2014, 15(Suppl 5):S4  doi:10.1186/1471-2164-15-S5-S4


The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2164/15/S5/S4


Published:14 July 2014

© 2014 Campo et al.; licensee BioMed Central Ltd. 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2

Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2 | Hepatitis C New Drugs Review | Scoop.it

Hepatitis C virus (HCV) is a significant public health concern with approximately 160 million people infected worldwide1. HCV infection often results in chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. No vaccine is available and current therapies are effective against some, but not all, genotypes. HCV is an enveloped virus with two surface glycoproteins (E1 and E2). E2 binds to the host cell through interactions with scavenger receptor class B type I (SR-BI) and CD81, and serves as a target for neutralizing antibodies2, 3, 4. Little is known about the molecular mechanism that mediates cell entry and membrane fusion, although E2 is predicted to be a class II viral fusion protein. Here we describe the structure of the E2 core domain in complex with an antigen-binding fragment (Fab) at 2.4 Å resolution. The E2 core has a compact, globular domain structure, consisting mostly of β-strands and random coil with two small α-helices. The strands are arranged in two, perpendicular sheets (A and B), which are held together by an extensive hydrophobic core and disulphide bonds. Sheet A has an IgG-like fold that is commonly found in viral and cellular proteins, whereas sheet B represents a novel fold. Solution-based studies demonstrate that the full-length E2 ectodomain has a similar globular architecture and does not undergo significant conformational or oligomeric rearrangements on exposure to low pH. Thus, the IgG-like fold is the only feature that E2 shares with class II membrane fusion proteins. These results provide unprecedented insights into HCV entry and will assist in developing an HCV vaccine and new inhibitors.

Krishan Maggon 's insight:

Structural determination of the HCV may provide us with additional targets for new class of antiviral drugs

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How Gilead Sciences Can Deliver A Double: Part Two

How Gilead Sciences Can Deliver A Double: Part Two | Hepatitis C New Drugs Review | Scoop.it
Last month, Eugene Groysman made the case that Gilead Sciences (NASDAQ:GILD) can double its stock price because of high demand for its new Hepatitis-C drug, Sovaldi, even though it costs $84,000 per treatment. Eugene has an exceptional long-term investment track record so when he tells me how a stock can double I pay attention, and then I verify. When I research stocks, the opinions I value most highly come from those who have taken a position in the stock and have made money on it. After all, if the person expressing an opinion about the stock does not have a strong enough conviction to make a trade on it, why should we? And, if they have made trades on the stock, but have not made any money, why should we follow their lead?

Via Marco Antonio Gonzalez
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Marco Antonio Gonzalez's curator insight, July 11, 11:31 AM

About Gilead (Part Two)

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New Hepatitis C Therapies: The Toolbox, Strategies, and Challenges

Therapy for hepatitis C is undergoing a revolution. Several new drugs against the hepatitis C virus (HCV) have reached the market and many others, including direct-acting antivirals and host-targeted agents, are in phase II or III clinical development. All-oral, interferon-free combinations of drugs are expected to cure more than 90% of infections. A vast amount of data from clinical trials are presented regularly at international conferences or released to the press before peer-review, creating confusion in the viral hepatitis field. The goal of this review is to clarify the current stage of HCV therapy and drug development. This review describes the different classes of drugs and their mechanisms and properties, as well as treatment strategies in development, including those that are interferon-based and interferon-free. HCV treatment options that will be available in 2014–2015 are presented for each genotype. A number of unanswered questions and challenges remain, such as how to treat special populations, the role of ribavirin in interferon-free regimens, the role of HCV resistance in treatment failures, and how to best re-treat patients who failed on treatment. Strategic choices, cost issues, HCV screening, and improving access to care in resource-constrained areas also are discussed.

 KeywordsDirect-Acting Antivirals; Interferon-Free Regimens; Sofosbuvir; Simeprevir; DaclatasvirAbbreviations used in this paperDAA, direct-acting antiviral; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HTA, host-targeted agent; IFN, interferon; RdRp, RNA–dependent RNA polymerase; SVR, sustained virologic 
Krishan Maggon 's insight:
Gastroenterology

Volume 146, Issue 5, May 2014, Pages 1176–1192

 

Reviews and Perspectives New Hepatitis C Therapies: The Toolbox, Strategies, and Challenges Jean–Michel Pawlotsky,  Show more DOI: 10.1053/j.gastro.2014.03.003
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Studies on the role of NS3 and NS5A non-structural genes of hepatitis C virus genotype 3a local isolates in apoptosis

Studies on the role of NS3 and NS5A non-structural genes of hepatitis C virus genotype 3a local isolates in apoptosis | Hepatitis C New Drugs Review | Scoop.it
International Journal of Infectious Diseases, Volume null, Issue null, Pages null, null, Authors:Sabeen Sabri; Muhammad Idrees; Shazia Rafique; Amjad Ali; Muhammad Iqbal

 

SummaryBackground

Hepatitis C virus (HCV) is the causative agent of chronic liver diseases, which usually lead to liver fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Among the non-structural genes of HCV, NS3 and NS5A play important roles in apoptosis. The NS3 and NS5A genes of HCV interact with the p53 tumor suppressor gene differentially. The objective of this study was to analyze the interaction of NS3 and NS5A genes of HCV genotype 3a with the p53 gene, subgenomic HCV replicons harboring NS3 and NS5A genes.

Methods

Huh-7 cell lines stably expressing NS3 and NS5A genes were generated. The stable cell lines were confirmed by Western blot, reverse transcriptase PCR, and immunofluorescence assay. HCV NS3- and NS5A-expressing cell lines were transfected with p53-expressing clone.

Results

NS3 and NS5A both interact with p53 by down-regulating the expression of the p53 gene. In HCV subgenomic harboring cells, the interaction of NS3 and NS5A with p53 was observed consistently. The suppression of p53 gene expression by NS3 and NS5A was observed significantly as compared with NS3- and NS5A-negative control Huh-7 cells.

Conclusion

It is concluded that both of the non-structural genes, NS3 and NS5A, of HCV play important roles in the hepatocarcinogenesis of HCV by interacting directly or indirectly in different manners with the p53 gene.

 KeywordsHepatitis C virus; Liver cirrhoses; HCC; Non-structural proteins; Huh-7 cell lines; p53 gene 
Krishan Maggon 's insight:
Studies on the role of NS3 and NS5A non-structural genes of hepatitis C virus genotype 3a local isolates in apoptosisSabeen Sabria, Muhammad Idreesb, , , Shazia Rafiquec, Amjad Alid, Muhammad Iqbalc Show more
International Journal of Infectious Diseases

Volume 25, August 2014, Pages 38–44

 DOI: 10.1016/j.ijid.2014.01.010
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