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CDC DVH - Know More Hepatitis - Campaign Resources

CDC DVH - Know More Hepatitis - Campaign Resources | Hepatitis C New Drugs Review | Scoop.it
CDC DVH - Know More Hepatitis - Campaign Resources (Find more resources on #hepatitis C from @cdchep http://t.co/2SeTFwn2tT)
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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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Gilead, Merck And Achillion/J&J Square Off In An HCV 'Nuc'lear Showdown - Seeking Alpha

Gilead, Merck And Achillion/J&J Square Off In An HCV 'Nuc'lear Showdown - Seeking Alpha | Hepatitis C New Drugs Review | Scoop.it
Some years ago, it became clear that HCV therapy would follow a similar paradigm as HIV, with the standard of care consisting of a multi-drug combination.

 

SummaryComparison of 7-day monotherapy of Sovaldi vs. MK-3682 and ACH 3422 indicate a rate of viral clearance of Sovaldi > MK-3682 > ACH 3422.Gilead will be reporting Phase 3 data on GS-5816 with Sovaldi in 3Q15 and could have this pan-genotypic combo on the market by the end of 2016.Merck initiated a Phase 2 study with their triple combo in GT3 patients and could field a best-in-class pan-genotypic regimen in 2018, some two years behind Gilead's next generation.Achillion’s nuke ACH 3422 suffers from poor bioavailability, has a tenuous IP position, and a slow pace of development.JNJ’s nucleotide AL-335 acquired from Alios is in Phase 1 and, with access now to ACH 3102, JNJ could have a pan-genotypic therapy approved in the 2019 to 2020 time frame.
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CDC DVH - Division of Viral Hepatitis - May is Hepatitis Awareness Month

CDC DVH - Division of Viral Hepatitis - May is Hepatitis Awareness Month | Hepatitis C New Drugs Review | Scoop.it
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Burden-of-Hepatitis-C.pdf

Hepatitis C is an infectious disease, caused by the hepatitis C virus, which primarily affects the liver. The disease is often asymptomatic and only progresses slowly. An estimated 160 million persons may be infected worldwide and the corresponding estimate for the European Union is 5.5 million.

 

Today’s prevalent cases were mainly infected through blood transfusion and unsafe medical procedures before 1989 when the disease was yet to be discovered. Due to the slow progressive nature of the disease, those infected before 1989 now find themselves in more advanced stages of the chronic disease and run a higher risk of developing liver cirrhosis or related complications.

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Eur. Liver Patients Association

 

http://www.elpa-info.org/elpa-news---reader/items/elpa-launch-event-action-plan-and-burden-of-hepatitis-c.html

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Natural Killer Cells Promote Long-Term Hepatobiliary Inflammation in a Low-Dose Rotavirus Model of Experimental Biliary Atresia

Natural Killer Cells Promote Long-Term Hepatobiliary Inflammation in a Low-Dose Rotavirus Model of Experimental Biliary Atresia | Hepatitis C New Drugs Review | Scoop.it

by James E. Squires, Pranavkumar Shivakumar, Reena Mourya, Kazuhiko Bessho, Stephanie Walters, Jorge A. Bezerra

Abstract

Biliary atresia is a rapidly progressive obstructive cholangiopathy of infants. Mechanistic studies in the mouse model of Rhesus rotavirus (RRV)-induced biliary atresia have linked the importance of effector lymphocytes to the pathogenesis of extrahepatic bile duct (EHBD) injury and obstruction in experimental biliary atresia; however, studies of the progressive liver injury have been limited by early death of newborn mice. Here, we aimed to determine 1) if a lower inoculum of RRV induces obstruction of EHBDs while allowing for ongoing liver inflammation, and 2) if NK cells regulate intrahepatic injury. The administration of 0.25x106 fluorescence forming units of RRV induced an obstructive extrahepatic cholangiopathy, but allowed for restoration of the duct epithelium, increased survival, and the development of a progressive intrahepatic inflammatory injury with molecular and cellular signatures equivalent to the traditional infectious model. Investigating the mechanisms of liver injury, we found that NK cell depletion at the onset of jaundice decreased liver inflammation, suppressed the expression of fibrosis and inflammation/immunity genes, lowered plasma ALT and bilirubin and improved survival.

Conclusions

Lower inoculation of RRV-induced progressive liver injury and fibrosis via NK cells. These findings point to the potential use of NK cell-depleting strategies to block progression of liver disease in biliary atresia.

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Citation: Squires JE, Shivakumar P, Mourya R, Bessho K, Walters S, Bezerra JA (2015) Natural Killer Cells Promote Long-Term Hepatobiliary Inflammation in a Low-Dose Rotavirus Model of Experimental Biliary Atresia. PLoS ONE 10(5): e0127191. doi:10.1371/journal.pone.0127191

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Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle

Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycle | Hepatitis C New Drugs Review | Scoop.it
Highlights

 

Changes in membrane morphology studied by 2H and 31P Solid-state NMR.

Bilayer charge influences the oligomeric state of the amphipathic helix AH2 from NS4B.

Interaction of AH2 with charged lipid membranes reduces strain within bilayer.

AH2 from NS4B is involved in membrane remodelling and membranous web formation.

Lipid bilayer/NS4B interactions may regulate Hepatitis C virus lifecycle.

 

Abstract

The non-structural protein 4B (NS4B) from Hepatitis C virus (HCV) plays a pivotal role in the remodelling of the host cell's membranes, required for the formation of the viral replication complex where genome synthesis occurs. NS4B is an integral membrane protein that possesses a number of domains vital for viral replication. Structural and biophysical studies have revealed that one of these, the second amphipathic N-terminal helix (AH2), plays a key role in these remodelling events. However, there is still limited understanding of the mechanism through which AH2 promotes these changes. Here we report on solid-state NMR and molecular dynamics studies that demonstrate that AH2 promotes the clustering of negatively charged lipids within the bilayer, a process that reduces the strain within the bilayer facilitating the remodelling of the lipid bilayer. Furthermore, the presence of negatively charged lipids within the bilayer appears to promote the disassociation of AH2 oligomers, highlighting a potential role for lipid recruitment in regulating NS protein interactions.

Krishan Maggon 's insight:

 

 

 

 

Biochimica et Biophysica Acta (BBA) - Biomembranes

Volume 1848, Issue 8, August 2015, Pages 1671–1677

 Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state — Implications for the Hepatitis C virus life cycleEsther L. Ashworth Briggsa, Rafael G.B. Gomesa, b, Malaz Elhusseinc, William Colliera, I. Stuart Findlowa, Syma Khalidc, Chris J. McCormickb, , , Philip T.F. Williamsona, ,  Open Access funded by Wellcome TrustUnder a Creative Commons license Show moredoi:10.1016/j.bbamem.2015.04.015
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Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01 - Nature.com

Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01 - Nature.com | Hepatitis C New Drugs Review | Scoop.it

The Pharmacogenomics Journal

 

Abstract

 

Lapatinib is associated with a low incidence of serious liver injury. Previous investigations have identified and confirmed the Class II allele HLA-DRB1*07:01 to be strongly associated with lapatinib-induced liver injury; however, the moderate positive predictive value limits its clinical utility. To assess whether additional genetic variants located within the major histocompatibility complex locus or elsewhere in the genome may influence lapatinib-induced liver injury risk, and potentially lead to a genetic association with improved predictive qualities, we have taken two approaches: a genome-wide association study and a whole-genome sequencing study. This evaluation did not reveal additional associations other than the previously identified association for HLA-DRB1*07:01. The present study represents the most comprehensive genetic evaluation of drug-induced liver injury (DILI) or hypersensitivity, and suggests that investigation of possible human leukocyte antigen associations with DILI and other hypersensitivities represents an important first step in understanding the mechanism of these events.

Krishan Maggon 's insight:

The Pharmacogenomics Journal advance online publication 19 May 2015; doi: 10.1038/tpj.2015.40

Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01
OPEN

L R Parham1, L P Briley1, L Li1, J Shen1, P J Newcombe2, K S King1, A J Slater1, A Dilthey3, Z Iqbal3, G McVean3, C J Cox2, M R Nelson1 and C F Spraggs2

1GlaxoSmithKline Research & Development, Research Triangle Park, NC, USA2GlaxoSmithKline Research & Development, Stevenage, UK3Department of Statistics, University of Oxford, Oxford, UK

Correspondence: Dr CF Spraggs, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. E-mail: colin.f.spraggs@gsk.com

Received 19 November 2014; Revised 13 February 2015; Accepted 26 March 2015
Advance online publication 19 May 2015

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The Pharmacogenomics Journal advance online publication 19 May 2015; doi: 10.1038/tpj.2015.40

Comprehensive genome-wide evaluation of lapatinib-induced liver injury yields a single genetic signal centered on known risk allele HLA-DRB1*07:01
OPEN

L R Parham1, L P Briley1, L Li1, J Shen1, P J Newcombe2, K S King1, A J Slater1, A Dilthey3, Z Iqbal3, G McVean3, C J Cox2, M R Nelson1 and C F Spraggs2

1GlaxoSmithKline Research & Development, Research Triangle Park, NC, USA2GlaxoSmithKline Research & Development, Stevenage, UK3Department of Statistics, University of Oxford, Oxford, UK

Correspondence: Dr CF Spraggs, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK. E-mail: colin.f.spraggs@gsk.com

Received 19 November 2014; Revised 13 February 2015; Accepted 26 March 2015
Advance online publication 19 May 2015

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How We’re Curing The Incurable

How We’re Curing The Incurable | Hepatitis C New Drugs Review | Scoop.it
For the past 25 years, hepatitis C has remained largely incurable and often fatal for the world’s 170 million patients with the disease.
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DCV/ASV/BCV for HCV Infection With Cirrhosis

DCV/ASV/BCV for HCV Infection With Cirrhosis | Hepatitis C New Drugs Review | Scoop.it
This open-label uncontrolled study of patients with chronic HCV genotype 1 infection and cirrhosis reports high rates of SVR12 in those who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin.

 

Abstract   JAMA

 

Importance  Effective and well-tolerated, interferon-free regimens are needed for treatment of patients with chronic hepatitis C virus (HCV) infection and cirrhosis.

Objective  All-oral therapy with daclatasvir (nonstructural protein 5A [NS5A] inhibitor), asunaprevir (NS3 protease inhibitor), and beclabuvir (nonnucleoside NS5B inhibitor), with or without ribavirin, was evaluated in patients with HCV genotype 1 infection and compensated cirrhosis.

Design, Setting, and Participants  The UNITY-2 study was conducted between December 2013 and October 2014 at 49 outpatient sites in the United States, Canada, France, and Australia. Patients were treated for 12 weeks, with 24 weeks of follow-up after completion of treatment. Adult patients with cirrhosis were enrolled in 2 cohorts: HCV treatment-naive or HCV treatment-experienced. Statistical analyses were based on historical controls; there were no internal controls.

Interventions  All patients received twice-daily treatment with the fixed-dose combination of daclatasvir (30 mg), asunaprevir (200 mg), and beclabuvir (75 mg). In addition, patients within each cohort were stratified according to HCV genotype 1 subtype (1a or 1b) and randomly assigned (1:1) to receive double-blinded weight-based ribavirin (1000-1200 mg/d) or matching placebo.

Main Outcomes and Measures  Sustained virologic response at posttreatment week 12 (SVR12).

 

Results  One hundred twelve patients in the treatment-naive group and 90 patients in the treatment-experienced group were treated and included in the analysis. Enrolled patients were 88% white with a median age of 58 years (treatment-naive group) or 60 years (treatment-experienced group); 74% had genotype 1a infection. SVR12 rates were 98% (97.5% CI, 88.9%-100%) for patients in the treatment-naive group and 93% (97.5% CI, 85.0%-100.0%) for those in the treatment-experienced group when ribavirin was included in the regimen. With the fixed-dose combination alone, response rates were 93% (97.5% CI, 85.4%-100.0%) for patients in the treatment-naive group and 87% (97.5% CI, 75.3%-98.0%) for those in the treatment-experienced group. Three serious adverse events were considered to be treatment related and there were 4 adverse event–related discontinuations. Treatment-emergent grade 3 or 4 alanine aminotransferase elevations were observed in 4 patients, of which 1 had concomitant total bilirubin elevation.

Conclusions and Relevance  In this open-label uncontrolled study, patients with chronic HCV genotype 1 infection and cirrhosis who received a 12-week oral fixed-dose regimen of daclatasvir, asunaprevir, and beclabuvir, with or without ribavirin, achieved high rates of SVR12.

Krishan Maggon 's insight:
Original Investigation | May 5, 2015Daclatasvir in Combination With Asunaprevir and Beclabuvir for Hepatitis C Virus Genotype 1 Infection With Compensated CirrhosisAndrew J. Muir, MD1; Fred Poordad, MD2; Jacob Lalezari, MD3; Gregory Everson, MD4; Gregory J. Dore, MBBS, MPH, PhD5,6; Robert Herring, MD7; Aasim Sheikh, MD8; Paul Kwo, MD9; Christophe Hézode, MD, PhD10; Paul J. Pockros, MD11; Albert Tran, MD, PhD12,13; Joseph Yozviak, DO14; Nancy Reau, MD15; Alnoor Ramji, MD16; Katherine Stuart, MBBS, PhD17; Alexander J. Thompson, MBBS, PhD18,19; John Vierling, MD20; Bradley Freilich, MD21; James Cooper, MD22; Wayne Ghesquiere, MD23; Rong Yang, PhD24; Fiona McPhee, PhD25; Eric A. Hughes, MD, PhD24; E. Scott Swenson, MD, PhD25; Philip D. Yin, MD, PhD25[+] Author AffiliationsJAMA. 2015;313(17):1736-1744. doi:10.1001/jama.2015.3868.
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Clinical marvel, financial failure: the tragic tale of sofosbuvir | The Lancet Global Health Blog

Clinical marvel, financial failure: the tragic tale of sofosbuvir | The Lancet Global Health Blog | Hepatitis C New Drugs Review | Scoop.it
RT @LancetGH: Clinical marvel, financial failure: the tragic tale of #sofosbuvir http://t.co/nZHrQpuNLk #HCV

 

The story begins in 1998 when research scientists Dr Raymond Schinazi and Dr Dennis Liotta set up Pharmasset, a small US-based company, which focused on developing anti-viral medications. The company developed a novel oral hepatitis C drug, then known as PSI-7977, which showed huge promise, and led Gilead Sciences to acquire Pharmasset in November 2011—for $11 billion. This was an unprecedented outlay, especially since the drug was still in phase 2 clinical trials. Yet a little over 3 years later—and after only 12 months on the market—sofosbuvir had recorded global sales worth $10.3 billion; it is now on track to become one of the most profitable drugs of all time.

 

Revenue is predominantly generated from the USA where sofosbuvir retails at $84,000for a standard 12-week course. This sort of price is generally the preserve of orphan diseases, in which R&D costs must be recouped from a relatively small pool of patients. Yet 130-150 million people across the world have chronic hepatitis C, including 3.2 million people in the USA. It is therefore far from a rare disease and most relevant patents don’t expire for another 15 years.

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There is a certain irony that, like many drugs, sofosbuvir began life in university laboratories (Cardiff University, UK, and Emory University, USA), funded at least in part by the same governments which are now struggling to pay the prices set. 

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Gilead Sciences - No Need To Gild The Lily (GILD) - Seeking Alpha

Gilead Sciences - No Need To Gild The Lily (GILD) - Seeking Alpha | Hepatitis C New Drugs Review | Scoop.it
After announcing record earnings last week, it's a mystery to me why the market doesn't respond to Gilead Sciences (NASDAQ:GILD) results.
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Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture

Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture | Hepatitis C New Drugs Review | Scoop.it
by Ramazan Kurt, Partha K. Chandra, Fatma Aboulnasr, Rajesh Panigrahi, Pauline Ferraris, Yucel Aydin, Krzysztof Reiss, Tong Wu, Luis A.

 

AbstractBackground

Hepatic steatosis is a risk factor for both liver disease progression and an impaired response to interferon alpha (IFN-α)-based combination therapy in chronic hepatitis C virus (HCV) infection. Previously, we reported that free fatty acid (FFA)-treated HCV cell culture induces hepatocellular steatosis and impairs the expression of interferon alpha receptor-1 (IFNAR1), which is why the antiviral activity of IFN-α against HCV is impaired.

Aim

To investigate the molecular mechanism by which IFNAR1 expression is impaired in HCV cell culture with or without free fatty acid-treatment.

Method

HCV-infected Huh 7.5 cells were cultured with or without a mixture of saturated (palmitate) and unsaturated (oleate) long-chain free fatty acids (FFA). Intracytoplasmic fat accumulation in HCV-infected culture was visualized by oil red staining. Clearance of HCV in FFA cell culture treated with type I IFN (IFN-α) and Type III IFN (IFN-λ) was determined by Renilla luciferase activity, and the expression of HCV core was determined by immunostaining. Activation of Jak-Stat signaling in the FFA-treated HCV culture by IFN-α alone and IFN-λ alone was examined by Western blot analysis and confocal microscopy. Lysosomal degradation of IFNAR1 by chaperone-mediated autophagy (CMA) in the FFA-treated HCV cell culture model was investigated.

 

Results

FFA treatment induced dose-dependent hepatocellular steatosis and lipid droplet accumulation in HCV-infected Huh-7.5 cells. FFA treatment of infected culture increased HCV replication in a concentration-dependent manner. Intracellular lipid accumulation led to reduced Stat phosphorylation and nuclear translocation, causing an impaired IFN-α antiviral response and HCV clearance. Type III IFN (IFN-λ), which binds to a separate receptor, induces Stat phosphorylation, and nuclear translocation as well as antiviral clearance in FFA-treated HCV cell culture. We show here that the HCV-induced autophagy response is increased in FFA-treated cell culture. Pharmacological inhibitors of lysosomal degradation, such as ammonium chloride and bafilomycin, prevented IFNAR1 degradation in FFA-treated HCV cell culture. Activators of chaperone-mediated autophagy, including 6-aminonicotinamide and nutrient starvation, decreased IFNAR1 levels in Huh-7.5 cells. Co-immunoprecipitation, colocalization and siRNA knockdown experiments revealed that IFNAR1 but not IFNLR1 interacts with HSC70 and LAMP2A, which are core components of chaperone-mediated autophagy (CMA).

Conclusion

Our study presents evidence indicating that chaperone-mediated autophagy targets IFNAR1 degradation in the lysosome in FFA-treated HCV cell culture. These results provide a mechanism for why HCV induced autophagy response selectively degrades type I but not the type III IFNAR1.

Krishan Maggon 's insight:

Citation: Kurt R, Chandra PK, Aboulnasr F, Panigrahi R, Ferraris P, Aydin Y, et al. (2015) Chaperone-Mediated Autophagy Targets IFNAR1 for Lysosomal Degradation in Free Fatty Acid Treated HCV Cell Culture. PLoS ONE 10(5): e0125962. doi:10.1371/journal.pone.0125962

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Johnson & Johnson Just Stepped Up Its Hepatitis C Game - Motley Fool

Johnson & Johnson Just Stepped Up Its Hepatitis C Game - Motley Fool | Hepatitis C New Drugs Review | Scoop.it
Johnson & Johnson has inked a licensing deal with Achillion Pharmaceuticals that could threaten Gilead Sciences market share in hepatitis C. Should Gilead investors worry?
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Optimism for patients with genotype 4 HCV infection: Clinical trials with direct-acting antivirals finally available - Journal of Hepatology

Optimism for patients with genotype 4 HCV infection: Clinical trials with direct-acting antivirals finally available - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it
Peter J. Ruane, Dani Ain, Richard Stryker, Raymond Meshrekey, Mina Soliman, Peter R. Wolfe, Joseph Riad, Sameh Mikhail, Kathryn Kersey, Deyuan Jiang, Benedetta Massetto, Brian Doehle, Brian J. Kirby, Steven J. Knox, John G. McHutchison, William T. SymondsSofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestryJournal of Hepatology, Volume 62, Issue 5, May 2015, Pages 1040-1046 Purchase PDF (703 K)Christophe Moreno, Christophe Hezode, Patrick Marcellin, Stefan Bourgeois, Sven Francque, Didier Samuel, Fabien Zoulim, Jean-Didier Grange, Umesh Shukla, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Bart Fevery, Monika Peeters, Maria Beumont, Wolfgang JessnerEfficacy and safety of simeprevir with PegIFN/ribavirin in naïve or experienced patients infected with chronic HCV genotype 4Journal of Hepatology, Volume 62, Issue 5, May 2015, Pages 1047-1055 Purchase PDF (862 K)  Supplementary contentTarek Hassanein, Karen D. Sims, Michael Bennett, Norman Gitlin, Eric Lawitz, Tuan Nguyen, Lynn Webster, Zobair Younossi, Howard Schwartz, Paul J. Thuluvath, Helen Zhou, Bhaskar Rege, Fiona McPhee, Nannan Zhou, Megan Wind-Rotolo, Ellen Chung, Amber Griffies, Dennis M. Grasela, David F. GardinerA randomized trial of daclatasvir in combination with asunaprevir and beclabuvir in patients with chronic hepatitis C virus genotype 4 infectionJournal of Hepatology, Volume 62, Issue 5, May 2015, Pages 1204-1206 Purchase PDF (333 K)  Supplementary contentReferred to byPeter J. Ruane, Dani Ain, Richard Stryker, Raymond Meshrekey, Mina Soliman, Peter R. Wolfe, Joseph Riad, Sameh Mikhail, Kathryn Kersey, Deyuan Jiang, Benedetta Massetto, Brian Doehle, Brian J. Kirby, Steven J. Knox, John G. McHutchison, William T. SymondsSofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestryJournal of Hepatology, Volume 62, Issue 5, May 2015, Pages 1040-1046 Purchase PDF (703 K)Christophe Moreno, Christophe Hezode, Patrick Marcellin, Stefan Bourgeois, Sven Francque, Didier Samuel, Fabien Zoulim, Jean-Didier Grange, Umesh Shukla, Oliver Lenz, Sivi Ouwerkerk-Mahadevan, Bart Fevery, Monika Peeters, Maria Beumont, Wolfgang JessnerEfficacy and safety of simeprevir with PegIFN/ribavirin in naïve or experienced patients infected with chronic HCV genotype 4Journal of Hepatology, Volume 62, Issue 5, May 2015, Pages 1047-1055 Purchase PDF (862 K)  Supplementary contentTarek Hassanein, Karen D. Sims, Michael Bennett, Norman Gitlin, Eric Lawitz, Tuan Nguyen, Lynn Webster, Zobair Younossi, Howard Schwartz, Paul J. Thuluvath, Helen Zhou, Bhaskar Rege, Fiona McPhee, Nannan Zhou, Megan Wind-Rotolo, Ellen Chung, Amber Griffies, Dennis M. Grasela, David F. GardinerA randomized trial of daclatasvir in combination with asunaprevir and beclabuvir in patients with chronic hepatitis C virus genotype 4 infectionJournal of Hepatology, Volume 62, Issue 5, May 2015, Pages 1204-1206 Purchase PDF (333 K)  Supplementary content
Krishan Maggon 's insight:

doi:10.1016/j.jhep.2015.03.003

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German IQWIG Dasabuvir in hepatitis C: Benefit in treatment naive HCV patients without cirrhosis

German IQWIG Dasabuvir in hepatitis C: Benefit in treatment naive HCV patients without cirrhosis | Hepatitis C New Drugs Review | Scoop.it

The drug dasabuvir (trade name Exviera) has been available since January 2015 for the treatment of adults with chronic hepatitis C infection. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether this drug offers an added benefit over the appropriate comparator therapy.

 

According to the findings, there are indications of an added benefit in patients who have not yet developed cirrhosis of the liver and who are infected with the hepatitis C virus (HCV) genotype 1a. In case of genotype 1b, this only applies to treatment-naive, but not to treatment-experienced patients. The extent of added benefit is non-quantifiable, however. No added benefit can be derived from the dossier for seven other Patient groups.

Krishan Maggon 's insight:

 The German Institute for Quality and Efficiency in Health Care (IQWiG)

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Janssen/J&J bet $1.1 billion on Achillion Hepatitis C R&D pipeline

Janssen/J&J bet $1.1 billion on Achillion  Hepatitis C R&D pipeline | Hepatitis C New Drugs Review | Scoop.it

NEW HAVEN, Conn., May 19, 2015 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) announced today that it has entered into a worldwide license and collaboration arrangement with Janssen Pharmaceuticals, Inc. (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, to develop and commercialize one or more of Achillion's lead hepatitis C virus (HCV) assets which include ACH-3102, ACH-3422, and sovaprevir.


Under the terms of the agreement, Achillion will grant Janssen an exclusive, worldwide license to develop and, upon regulatory approval, commercialize HCV products and regimens containing one or more of Achillion's HCV assets. Achillion is eligible to receive a number of payments based upon achievement of specified development, regulatory and sales milestones. Achillion is also eligible to receive tiered royalty percentages between mid-teens and low-twenties based upon future worldwide sales. Janssen will be responsible for all of the development costs within the collaboration and all subsequent costs related to commercialization of the HCV assets.

 

A key objective of the collaboration will be to develop a short-duration, highly effective, pan-genotypic, oral regimen for the treatment of HCV. An initial regimen that will be explored will feature Achillion's ACH-3102, a second-generation NS5A inhibitor currently in Phase 2 clinical studies that has been granted Fast Track designation by the U.S. Food and Drug Administration, in combination with an NS3/4A HCV protease inhibitor plus an NS5B HCV polymerase inhibitor from the collaboration.

 

Additionally, in an equity transaction separate to the exclusive license and collaboration arrangement, Johnson & Johnson Innovation - JJDC, Inc. will invest $225 million in Achillion and, in return, receive approximately 18.4 million newly issued, unregistered shares of Achillion at a price of $12.25 per share.


Krishan Maggon 's insight:
Achillion Enters Into Worldwide Collaboration for Hepatitis C With Janssen

 

- Transactions include up to $1.1 billion in potential development, regulatory and sales milestone payments and a separate equity investment -

- Achillion eligible for tieredroyalties between mid-teens and low-twenties on future worldwide sales -

- Janssen responsible for all development costs within the collaboration and all subsequent costs related to commercialization of the assets -

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Crucial Hepatitis C Replication Discovery Could Lead to Vital Treatments - MD Magazine

Crucial Hepatitis C Replication Discovery Could Lead to Vital Treatments - MD Magazine | Hepatitis C New Drugs Review | Scoop.it
Preventing the replication of the hepatitis C virus (HCV) may be a future reality thanks to an important exploration.
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Scientists identify crucial step in helping to prevent Hepatitis C virus ... - Phys.Org

Scientists identify crucial step in helping to prevent Hepatitis C virus ... - Phys.Org | Hepatitis C New Drugs Review | Scoop.it
New research from the University of Southampton has identified how changes in the cell membrane play a pivotal role in how the Hepatitis C virus replicates.
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Interaction between the NS4B amphipathic helix, AH2, and charged lipid headgroups alters membrane morphology and AH2 oligomeric state—Implications for the Hepatitis C virus life cycle," Biochimica et Biophysica Acta (BBA) - Biomembranes, Volume 1848, Issue 8, August 2015, Pages 1671-1677, ISSN 0005-2736, dx.doi.org/10.1016/j.bbamem.2015.04.015


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Long-term treatment outcomes of patients infected with Hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a Sustained Virological Response

Long-term treatment outcomes of patients infected with Hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a Sustained Virological Response | Hepatitis C New Drugs Review | Scoop.it
Abstract

Background. Achievement of a sustained virologic response (SVR) after treatment for Hepatitis C infection is associated with improved outcomes. This meta-analysis aimed to determine the impact of SVR on long-term mortality risk compared with non-responders in a range of populations.

Methods. An electronic search identified all studies assessing all-cause mortality in SVR and non-SVR patients. Eligible articles were stratified into general, cirrhotic, and HIV co-infected populations. The adjusted hazard ratio (95%CI) for mortality in patients achieving SVR versus non-SVR, and pooled estimates for the five-year mortality in each group were calculated.

Results. 31 studies (n=33,360) were identified as suitable for inclusion. Median follow-up time was 5.4 years (IQR 4.9-7.5) across all studies. The adjusted hazard ratio of mortality for patients achieving SVR versus non-SVR was 0.50 (95%CI 0.37-0.67) in the general population, 0.26 (95%CI 0.18-0.74) in the cirrhotic group, and 0.21 (0.10-0.45) in the co-infected group. The pooled five-year mortality rates were significantly lower for patients achieving SVR compared with non-SVR in all three populations.

Conclusions. The results suggest that there is a significant survival benefit of achieving an SVR compared with unsuccessful treatment in a range of HCV-infected populations.

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Clin Infect Dis. (2015)doi: 10.1093/cid/civ396First published online: May 17, 2015 Long-term treatment outcomes of patients infected with Hepatitis C virus: a systematic review and meta-analysis of the survival benefit of achieving a Sustained Virological ResponseBryony Simmons1, Jawaad Saleem1, Katherine Heath1, Graham S. Cooke1, and Andrew Hill2

+Author Affiliations

1Division of Medicine, Imperial College London, London, UK2Pharmacology and Therapeutics, Liverpool University, Liverpool, UKContact information for corresponding author: Ms Bryony Simmons MPH, St Mary's Campus, Imperial College London, Norfolk Place, London, W2 1PG. Email:bryony.simmons13@imperial.ac.uk
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Investing in hepatitis C drugs could save the economy billions, researchers suggest

Investing in hepatitis C drugs could save the economy billions, researchers suggest | Hepatitis C New Drugs Review | Scoop.it
New hepatitis C drugs may be more expensive but have have higher cure rates and fewer side effects, and could save the US and five European countries $3.2 billion a year.

Via #BBBundyBlog #NOMORELIES Tom Woods #Activist Award #Scoopiteer >20,000 Sources >250K Connections http://goo.gl/ruHO3Q
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New Hope for Patients with Hepatitis C

New Hope for Patients with Hepatitis C | Hepatitis C New Drugs Review | Scoop.it
New and forthcoming medicines can halt the progression of hepatitis C and, in many cases, provide a cure.
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Hepatitis C Virus Gene Sequencing as a Tool for Precise Genotyping in the Era of New Direct Antiviral Agents - Ceccherini Silberstein - Hepatology - Wiley Online Library

Hepatitis C Virus Gene Sequencing as a Tool for Precise Genotyping in the Era of New Direct Antiviral Agents - Ceccherini Silberstein - Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it
RT @HEP_Journal: Hepatitis C Virus Gene Sequencing as a Tool for Precise Genotyping in the Era of New Direct Ant... http://t.co/pHoDCiKato
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Hepatitis C Virus Gene Sequencing as a Tool for Precise Genotyping in the Era of New Direct Antiviral AgentsFrancesca Ceccherini Silberstein1,*, Velia Chiara Di Maio1, Marianna Aragri1, Marco Ciotti2, Valeria Cento1 andCarlo Federico Perno1,2

DOI: 10.1002/hep.27895

© 2015 by the American Association for the Study of Liver Diseases

Issue

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

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Viral Hepatitis Home

Viral Hepatitis Home | Hepatitis C New Drugs Review | Scoop.it
The Department of Veterans Affairs (VA) leads the country in hepatitis screening, testing, treatment, research and prevention. An extensive list of documents can be found on this site intended for patient and provider alike.
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Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a systematic review and meta-analysis - The Lancet Infectious Diseases

Hepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a systematic review and meta-analysis - The Lancet Infectious Diseases | Hepatitis C New Drugs Review | Scoop.it

Abstract  Lancet Inf. Dis

 

Findings

We included 213 studies from 33 countries in sub-Saharan Africa, comprising 287 separate cohorts with 1 198 167 individuals. The pooled HCV seroprevalence from all cohorts was 2·98% (95% CI 2·86–3·10). The pooled HCV seroprevalence was 2·65% (95% CI 2·53–2·78) across all 185 low-risk cohorts, 3·04% (2·23–3·84) in antenatal clinic groups, 1·99% (1·86–2·12) in blood donors, but 6·9% (6·1–7·5) in other general population cohorts. The pooled seroprevalence of HCV was 11·87% (95% CI 7·05–16·70) across all high-risk groups and 9·95% (6·79–13·11) in patients with liver disease. 101 cohorts included HIV-positive samples tested for HCV (42 648 individuals), with a pooled seroprevalence of 5·73% (95% CI 4·90–6·56).

Interpretation

We recorded a high seroprevalence of HCV across populations of sub-Saharan Africa, including in HIV-positive adults, with evidence of regional variation in the general population. Monitoring of antenatal HCV prevalence might be a helpful indicator of population trends in HCV infection; however, larger population surveys are needed to monitor these trends. Access to prevention and treatment needs to be improved for both monoinfected and co-infected individuals.

 

 

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The Lancet Infectious DiseasesHepatitis C seroprevalence and HIV co-infection in sub-Saharan Africa: a systematic review and meta-analysisV Bhargavi Rao, PhD, Nur Johari, BSc, Philipp du Cros, MRCP, Janey Messina, PhD, Nathan Ford, PhD†, Dr Graham S Cooke, PhD††These authors contributed equallyPublished Online: 05 May 2015DOI: http://dx.doi.org/10.1016/S1473-3099(15)00006-7 | Article Info

 

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Researchers discover HCV prevalent in sub-Saharan Africa - Healio

Researchers discover HCV prevalent in sub-Saharan Africa - Healio | Hepatitis C New Drugs Review | Scoop.it
Hepatitis C virus infection was seroprevalent in various populations across sub-Saharan Africa, especially among adults with HIV, according to newly published data in The Lancet Infectious Diseases.“Viral hepatitis is a huge problem in Africa, but...
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