Hepatitis C New D...
Follow
Find
15.8K views | +2 today
 
Scooped by Krishan Maggon
onto Hepatitis C New Drugs Review
Scoop.it!

US FDA puts hold on Vertex hepatitis study; shares fall - Reuters

US FDA puts hold on Vertex hepatitis study; shares fall
Reuters
Vertex said the U.S.
more...
No comment yet.
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#
Curated by Krishan Maggon
Your new post is loading...
Your new post is loading...
Scooped by Krishan Maggon
Scoop.it!

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"...
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Spontaneous and NCR mediated cytotoxicity are effector functions of distinct NK subsets in HCV infected chimpanzees - Verstrepen - Clinical & Experimental Immunology - Wiley Online Library

Spontaneous and NCR mediated cytotoxicity are effector functions of distinct NK subsets in HCV infected chimpanzees - Verstrepen - Clinical & Experimental Immunology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it

In humans, CD16 and CD56 are used to identify functionally distinct NK subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis? | Hepatitis C New Drugs Review | Scoop.it

Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and...

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Cooperation among viral variants helps Hepatitis C survive immune system attacks

Cooperation among viral variants helps Hepatitis C survive immune system attacks | Hepatitis C New Drugs Review | Scoop.it

May 27, 2015 Atlanta, GA A new study suggests that the Hepatitis C virus may use decoy viral variants to distract the body's natural defenses.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking

Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking | Hepatitis C New Drugs Review | Scoop.it
Abstract

The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe the discovery of novel potent HCV NS5B polymerase inhibitors by employing a virtual screening (VS) approach, which is based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In the RB-VS stage, after feature selection, a model with 16 descriptors was used. In the PB-VS stage, six energy-based pharmacophore (e-pharmacophore) models from different crystal structures of the NS5B polymerase with ligands binding at the palm I, thumb I and thumb II regions were used. In the DB-VS stage, the Glide SP and XP docking protocols with default parameters were employed. In the virtual screening approach, the RB-VS, PB-VS and DB-VS methods were applied in increasing order of complexity to screen the InterBioScreen database. From the final hits, we selected 5 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 5 compounds were found to inhibit NS5B polymerase with IC50 values of 2.01–23.84 μM and displayed anti-HCV activities with EC50 values ranging from 1.61 to 21.88 μM, and all compounds displayed no cellular cytotoxicity (CC50 > 100 μM) except compound N2, which displayed weak cytotoxicity with a CC50 value of 51.3 μM. The hit compound N2 had the best antiviral activity against HCV, with a selective index of 32.1. The 5 hit compounds with new scaffolds could potentially serve as NS5B polymerase inhibitors through further optimization and development.

 

Krishan Maggon 's insight:

Citation: Wei Y, Li J, Qing J, Huang M, Wu M, Gao F, et al. (2016) Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking. PLoS ONE 11(2): e0148181. doi:10.1371/journal.pone.0148181

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Ledipasvir/sofosbuvir fixed-dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus - Chuang - Journal of Gastroenterology and Hepatology - Wiley Online Library

Ledipasvir/sofosbuvir fixed-dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus - Chuang - Journal of Gastroenterology and Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it
Abstract
Background and Aim

Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic HCV infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the US, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients.

Methods

In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naive; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (+/−compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected.

Results

The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naive and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3–4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir.

Conclusions

Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history.

Krishan Maggon 's insight:

DOI: 10.1111/jgh.13305

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

HCV Genotyping from NGS Short Reads and Its Application in Genotype Detection from HCV Mixed Infected Plasma

HCV Genotyping from NGS Short Reads and Its Application in Genotype Detection from HCV Mixed Infected Plasma | Hepatitis C New Drugs Review | Scoop.it
Genotyping of hepatitis C virus (HCV) plays an important role in the treatment of HCV. As new genotype-specific treatment options become available, it has become increasingly important to have accurate HCV genotype and subtype information to ensure that the most appropriate treatment regimen is selected. Most current genotyping methods are unable to detect mixed genotypes from two or more HCV infections. Next generation sequencing (NGS) allows for rapid and low cost mass sequencing of viral genomes and provides an opportunity to probe the viral population from a single host. In this paper, the possibility of using short NGS reads for direct HCV genotyping without genome assembly was evaluated. We surveyed the publicly-available genetic content of three HCV drug target regions (NS3, NS5A, NS5B) in terms of whether these genes contained genotype-specific regions that could predict genotype. Six genotypes and 38 subtypes were included in this study. An automated phylogenetic analysis based HCV genotyping method was implemented and used to assess different HCV target gene regions. Candidate regions of 250-bp each were found for all three genes that have enough genetic information to predict HCV genotypes/subtypes. Validation using public datasets shows 100% genotyping accuracy. To test whether these 250-bp regions were sufficient to identify mixed genotypes, we developed a random primer-based method to sequence HCV plasma samples containing mixtures of two HCV genotypes in different ratios. We were able to determine the genotypes without ambiguity and to quantify the ratio of the abundances of the mixed genotypes in the samples. These data provide a proof-of-concept that this random primed, NGS-based short-read genotyping approach does not need prior information about the viral population and is capable of detecting mixed viral infection.
Krishan Maggon 's insight:

Citation: Qiu P, Stevens R, Wei B, Lahser F, Howe AYM, Klappenbach JA, et al. (2015) HCV Genotyping from NGS Short Reads and Its Application in Genotype Detection from HCV Mixed Infected Plasma. PLoS ONE 10(4): e0122082. doi:10.1371/journal.pone.0122082

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Evaluation of Biofield Modality on Viral Load of Hepatitis B and C Viruses

Evaluation of Biofield Modality on Viral Load of Hepatitis B and C Viruses | Hepatitis C New Drugs Review | Scoop.it

Official Full-Text Publication: Evaluation of Biofield Modality on Viral Load of Hepatitis B and C Viruses on ResearchGate, the professional network for scientists.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection - Journal of Medicinal Chemistry (ACS Publications)

Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection - Journal of Medicinal Chemistry (ACS Publications) | Hepatitis C New Drugs Review | Scoop.it

Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.5b00752

 

Recently, we reported that chlorcyclizine (CCZ, Rac-2), an over-the-counter antihistamine piperazine drug, possesses in vitro and in vivo activity against hepatitis C virus. Here, we describe structure–activity relationship (SAR) efforts that resulted in the optimization of novel chlorcyclizine derivatives as anti-HCV agents. Several compounds exhibited EC50 values below 10 nM against HCV infection, cytotoxicity selectivity indices above 2000, and showed improvedin vivo pharmacokinetic properties. The optimized molecules can serve as lead preclinical candidates for the treatment of hepatitis C virus infection and as probes to study hepatitis C virus pathogenesis and host–virus interaction.

Krishan Maggon 's insight:
Discovery, Optimization, and Characterization of Novel Chlorcyclizine Derivatives for the Treatment of Hepatitis C Virus Infection
Shanshan He†, Jingbo Xiao‡, Andrés E. Dulcey‡, Billy Lin†, Adam Rolt‡, Zongyi Hu†, Xin Hu‡, Amy Q. Wang‡, Xin Xu‡, Noel Southall‡, Marc Ferrer‡, Wei Zheng‡, T. Jake Liang*†, and Juan J. Marugan*‡
† Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, United States
‡ Division of Pre-Clinical Innovations, National Center for Advancing Translational Sciences, National Institutes of Health, 9800 Medical Center Drive, Rockville, Maryland 20850, United States
J. Med. Chem., Article ASAP
DOI: 10.1021/acs.jmedchem.5b00752
Publication Date (Web): November 24, 2015
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

European Commission Approves Daklinza (daclatasvir) for the Treatment of Genotype 1, 3 and 4 Chronic Hepatitis C Patients with HIV Coinfection, Advanced Cirrhosis and Post-liver Transplant Recurren...

European Commission Approves Daklinza (daclatasvir) for the Treatment of Genotype 1, 3 and 4 Chronic Hepatitis C Patients with HIV Coinfection, Advanced Cirrhosis and Post-liver Transplant Recurren... | Hepatitis C New Drugs Review | Scoop.it

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE:BMY) announced today that the European Commission has approved Daklinza for the treatment of chronic hepatitis C (HCV) in three new patient populations. The expanded label allows for the use of Daklinza in combination with sofosbuvir (with or without ribavirin, depending on the indication and HCV genotype) in HCV patients with decompensated cirrhosis, HIV-1 (human immunodeficiency virus) coinfection, and post-liver transplant recurrence of HCV in all 28 Member States of the European Union.


Daklinza is already approved by the European Commission for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic HCV infection in adults, and the Daklinza + sofosbuvir regimen is the only approved 12-week, all-oral treatment for genotype 3 HCV patients without cirrhosis. The new indications are based on data from the ALLY-1 clinical trial (in post-transplant patients and patients with advanced cirrhosis) and ALLY-2 clinical trial (in HIV-coinfected patients). 

Krishan Maggon 's insight:

Updated label provides additional treatment options for multiple HCV patient populations, including difficult-to-treat patients with decompensated cirrhosis


HIV/HCV coinfected patients experience more rapid fibrosis progression than mono-infected HCV patients

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

The Fight Against Hepatitis C

The Fight Against Hepatitis C | Hepatitis C New Drugs Review | Scoop.it

A diagnosis of hepatitis C, caused by the hepatitis C virus (HCV), doesn’t mean you have to face it alone.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models

Intrahepatic Tissue Implantation Represents a Favorable Approach for Establishing Orthotopic Transplantation Hepatocellular Carcinoma Mouse Models | Hepatitis C New Drugs Review | Scoop.it

Mouse models are commonly used for studying hepatocellular carcinoma (HCC) biology and exploring new therapeutic interventions.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Daclatasvir, Sofosbuvir, and Ribavirin for Hepatitis C Virus Genotype 3 and Advanced Liver Disease: A Randomized Phase III Study (ALLY-3+). - PubMed - NCBI

Daclatasvir, Sofosbuvir, and Ribavirin for Hepatitis C Virus Genotype 3 and Advanced Liver Disease: A Randomized Phase III Study (ALLY-3+). - PubMed - NCBI | Hepatitis C New Drugs Review | Scoop.it
Hepatology. 2016 Jan 28. doi: 10.1002/hep.28473. [Epub ahead of print]

 

Abstract

Patients with hepatitis C virus (HCV) genotype 3 infection, especially with advanced liver disease, are a challenging population in urgent need of optimally effective therapies. The combination of daclatasvir (DCV; pangenotypic NS5A inhibitor) and sofosbuvir (SOF; nucleotide NS5B inhibitor) for 12 weeks previously showed high efficacy (96%) in noncirrhotic genotype 3 infection. The phase III ALLY-3+ study (N = 50) evaluated DCV-SOF with ribavirin (RBV) in treatment-naive (n = 13) or treatment-experienced (n = 37) genotype 3 patients with advanced fibrosis (n = 14) or compensated cirrhosis (n = 36). Patients were randomized 1:1 to receive open-label DCV-SOF (60 + 400 mg daily) with weight-based RBV for 12 or 16 weeks. The primary endpoint was sustained virologic response at posttreatment week 12 (SVR12). SVR12 (intention-to-treat) was 90% overall (45/50): 88% (21/24) in the 12-week (91% observed) and 92% (24/26) in the 16-week group. All patients with advanced fibrosis achieved SVR12. SVR12 in patients with cirrhosis was 86% overall (31/36): 83% (15/18) in the 12-week (88% observed) and 89% (16/18) in the 16-week group; for treatment-experienced patients with cirrhosis, these values were 87% (26/30), 88% (14/16; 93% observed) and 86% (12/14), respectively. One patient (12-week group) did not enter posttreatment follow-up (death unrelated to treatment). There were 4 relapses (2 per group) and no virologic breakthroughs. The most common adverse events (AEs) were insomnia, fatigue and headache. There were no discontinuations for AEs, and no treatment-related serious AEs.

CONCLUSION:

The all-oral regimen of DCV-SOF-RBV was well tolerated and resulted in high and similar SVR12 after 12 or 16 weeks of treatment among genotype 3-infected patients with advanced liver disease, irrespective of prior HCV treatment experience. 

Krishan Maggon 's insight:
Hepatology. 2016 Jan 28. doi: 10.1002/hep.28473. [Epub ahead of print]
Daclatasvir, Sofosbuvir, and Ribavirin for Hepatitis C Virus Genotype 3 and Advanced Liver Disease: A Randomized Phase III Study (ALLY-3+).
Leroy V1, Angus P2, Bronowicki JP3, Dore GJ4, Hezode C5, Pianko S6, Pol S7, Stuart K8, Tse E9, McPhee F10, Bhore R11, Jesus Jimenez-Exposito M11,Thompson AJ12.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Daclatasvir, Sofosbuvir, and Ribavirin for Hepatitis C Virus Genotype 3 and Advanced Liver Disease: A Randomized Phase III Study (ALLY-3+) - Leroy - 2016 - Hepatology - Wiley Online Library

Daclatasvir, Sofosbuvir, and Ribavirin for Hepatitis C Virus Genotype 3 and Advanced Liver Disease: A Randomized Phase III Study (ALLY-3+) - Leroy - 2016 - Hepatology - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it

Daclatasvir + Sofosbuvir + Ribavirin for #HCV genotype 3 and advanced liver disease (ALLY-3+) https://t.co/rlS39zt0wn

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Chronic hepatitis C virus infection, a new cardiovascular risk factor? - Domont - 2016 - Liver International - Wiley Online Library

Chronic hepatitis C virus infection, a new cardiovascular risk factor? - Domont - 2016 - Liver International - Wiley Online Library | Hepatitis C New Drugs Review | Scoop.it

RT @rplanasv: Chronic hepatitis C virus infection, a new cardiovascular risk factor? ....

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort

Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort | Hepatitis C New Drugs Review | Scoop.it

Objective To assess the current frequency of ART-associated grade 3–4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV-infected patients with chronic hepatitis B and/or C, who start a new regimen of ART.

Krishan Maggon 's insight:

Citation: Neukam K, Mira JA, Collado A, Rivero-Juárez A, Monje-Agudo P, Ruiz-Morales J, et al. (2016) Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort. PLoS ONE 11(2): e0148104. doi:10.1371/journal.pone.0148104

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

F1000Research Article: Recent advances in understanding hepatitis C.

F1000Research Article: Recent advances in understanding hepatitis C. | Hepatitis C New Drugs Review | Scoop.it

Read the latest article version by Florian Douam, Qiang Ding, Alexander Ploss, at F1000Research.

 

Abstract

The past decade has seen tremendous progress in understanding hepatitis C virus (HCV) biology and its related disease, hepatitis C. Major advances in characterizing viral replication have led to the development of direct-acting anti-viral therapies that have considerably improved patient treatment outcome and can even cure chronic infection. However, the high cost of these treatments, their low barrier to viral resistance, and their inability to prevent HCV-induced liver cancer, along with the absence of an effective HCV vaccine, all underscore the need for continued efforts to understand the biology of this virus. Moreover, beyond informing therapies, enhanced knowledge of HCV biology is itself extremely valuable for understanding the biology of related viruses, such as dengue virus, which is becoming a growing global health concern. Major advances have been realized over the last few years in HCV biology and pathogenesis, such as the discovery of the envelope glycoprotein E2 core structure, the generation of the first mouse model with inheritable susceptibility to HCV, and the characterization of virus-host interactions that regulate viral replication or innate immunity. Here, we review the recent findings that have significantly advanced our understanding of HCV and highlight the major challenges that remain.

Krishan Maggon 's insight:

How to cite: Douam F, Ding Q and Ploss A. Recent advances in understanding hepatitis C [version 1; referees: 2 approved]. F1000Research 2016, 5(F1000 Faculty Rev):131 (doi: 10.12688/f1000research.7354.1)

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections

Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections | Hepatitis C New Drugs Review | Scoop.it
Abstract

: Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus–host balance, especially for some particular human leukocyte antigen (HLA) haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other persistent viruses, such as HIV and HCV.

Keywords:
 HTLV-1; HIV-1; HCV; genetic factors
Krishan Maggon 's insight:

Viruses 2016, 8(2), 38; doi: 10.3390/v8020038

Review
Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections
Tatiane Assone 1,2,*, Arthur Paiva 2, Luiz Augusto M. Fonseca 3 and Jorge Casseb 1,2,*
1
Laboratory of Dermatology and Immune deficiencies, Department of Dermatology, University of São Paulo Medical School, LIM56, Av. Dr. Eneas de Carvalho Aguiar 500, 3rd Floor, Building II, São Paulo, SP, Brazil
2
Institute of Tropical Medicine of São Paulo, São Paulo, Brazil
3
Department of Preventive Medicine, University of São Paulo Medical School, São Paulo, Brazil
*
Correspondence: Tel.: +55-11-3061-7194 (T.A. & J.C.); Fax: +55-11-3081-7190 (T.A. & J.C.)
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Natural killer cells in highly exposed hepatitis C-seronegative injecting drug users. - PubMed - NCBI

Natural killer cells in highly exposed hepatitis C-seronegative injecting drug users. - PubMed - NCBI | Hepatitis C New Drugs Review | Scoop.it

J Viral Hepat. 2016 Feb 1. doi: 10.1111/jvh.12511. [Epub ahead of print]

 

Abstract

Injecting drug use remains the major risk factor for hepatitis C (HCV) transmission. A minority of long-term injecting drug users remain seronegative and aviraemic, despite prolonged exposure to HCV - termed highly exposed seronegative subjects. Natural killer (NK) cells have been implicated in this apparent protection. A longitudinal nested, three group case-control series of subjects was selected from a prospective cohort of seronegative injecting drug users who became incident cases (n = 11), remained seronegative (n = 11) or reported transient high-risk behaviour and remained uninfected (n = 11). The groups were matched by age, sex and initial risk behaviour characteristics. Stored peripheral blood mononuclear cells were assayed in multicolour flow cytometry to enumerate natural killer cell subpopulations and to assess functional activity using Toll-like receptor ligands before measurement of activation, cytokine production and natural cytotoxicity receptor expression. Principal components were derived to describe the detailed phenotypic characteristics of the major NK subpopulations (based on CD56 and CD16 co-expression), before logistic regression analysis to identify associations with exposed, seronegative individuals. The CD56dim CD16+ (P = 0.05, OR 6.92) and CD56dim CD16- (P = 0.05, OR 6.07) principal components differed between exposed, seronegative individuals and pre-infection samples of the other two groups. These included CD56dimCD16+ and CD56dim CD16- subsets with CD56dim CD16+ IFN-γ and TNF-α on unstimulated cells, and CD56dim CD16- CD69+ , CD107a+ , IFN-γ and TNF-α following TLR stimulation. The cytotoxic CD56dim NK subset thus distinguished highly exposed, seronegative subjects, suggesting NK cytotoxicity may contribute to protection from HCV acquisition. Further investigation of the determinants of this association and prospective assessment of protection against HCV infection are warranted.

© 2016 John Wiley & Sons Ltd.

KEYWORDS:

hepatitis C; highly exposed seronegative; natural killer cells; principal component analysis; protective immunity

Krishan Maggon 's insight:
 
J Viral Hepat. 2016 Feb 1. doi: 10.1111/jvh.12511. [Epub ahead of print]
Natural killer cells in highly exposed hepatitis C-seronegative injecting drug users.
Mina MM1, Cameron B1, Luciani F1, Vollmer-Conna U2, Lloyd AR1; HITS-p investigators.
Collaborators (8)
 
Author information
1Inflammation and Infection Research Centre, School of Medical Sciences, University of New South Wales, Sydney, Australia.2School of Psychiatry, University of New South Wales, Sydney, Australia.
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Gilead Rises on Solid HCV Sales and Earnings Beat

Gilead Rises on Solid HCV Sales and Earnings Beat | Hepatitis C New Drugs Review | Scoop.it

Source: ThinkstockGilead Sciences Inc. (NASDAQ: GILD) reported fourth quarter financial results after the markets closed on Tuesday.

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Cohort study of the impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis - Journal of Hepatology

Cohort study of the impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis - Journal of Hepatology | Hepatitis C New Drugs Review | Scoop.it

[In press] Cohort study of the impact of DAA therapy in patients with chronic #HCV and decompensated #cirrhosis
https://t.co/BHzebsoh3t

 

AbstractBackground and Aims

All oral direct-acting antivirals (DAAs) effectively treat chronic hepatitis C virus (HCV) infection, but the benefits in advanced liver disease are unclear. We compared outcomes in treated and untreated patients with decompensated cirrhosis.

Methods

Patients with HCV and decompensated cirrhosis or at risk of irreversible disease were treated in an Expanded Access Programme (EAP) in 2014. Treatment, by clinician choice, was with sofosbuvir, ledipasvir or daclatasvir, with or without ribavirin. For functional outcome comparison, untreated patients with HCV and decompensated cirrhosis who were registered on a database 6 months before treatment was available were retrospectively studied. Primary endpoint was sustained virological response 12 weeks post antiviral treatment (treated cohort) and the secondary endpoint (both cohorts) was adverse outcomes (worsening in MELD score or serious adverse event) within 6 months.

Results

467 patients received treatment (409 decompensated cirrhosis). Viral clearance was achieved in 381 patients (81.6%) – 209 from 231 (90.5%) with genotype 1 and 132 from 192 (68.8%) with genotype 3. MELD scores improved in treated patients (mean change -0.85) but worsened in untreated patients (mean + 0.75) (p<0.0001). Patients with initial serum albumin <35 g/l, aged >65 or with low (<135 mmol/L) baseline serum sodium concentrations were least likely to benefit from therapy.

Conclusions

All oral DAAs effectively cured HCV in patients with advanced liver disease. Viral clearance was associated with improvement in liver function within 6 months compared to untreated patients. The longer term impact of HCV treatment in patients with decompensated cirrhosis remains to be determined.

 
Keywords:Hepatitis C virus, Sofosbuvir, Ledipasvir, Daclatasvir, MELD score, Decompensated cirrhosis
Krishan Maggon 's insight:
Cohort study of the impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis
Graham R. Fostera
,
 William L. Irvingab
,
Michelle C.M. Cheung, Alex J. Walker, Benjamin E. Hudson, Suman Verma, John McLauchlan, David J. Mutimer, Ashley Brown, William T.H. Gelson, Douglas C. MacDonald,  Kosh Agarwal
, on behalf of HCV Research UK
ajoint first authors
bTel.: 0115 823 0752
 
 
 
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Experts cite multiple contacts for hepatitis C virus exposure in Ghana

Experts cite multiple contacts for hepatitis C virus exposure in Ghana | Hepatitis C New Drugs Review | Scoop.it

West African residents have frequent opportunities for exposure to the hepatitis C virus, according to a comprehensive review in the journal PLOS ONE co-authored by infectious disease specialist Jennifer Layden, MD, PhD of ...

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Gilead Scares The Hell Out Of Me

Gilead Scares The Hell Out Of Me | Hepatitis C New Drugs Review | Scoop.it

Gilead Sciences has had a supreme couple of years in terms of increasing its business.Most of this has been in due to Sovaldi and Harvoni, their Hepatitis C cur

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Gilead Should Have Investors Giddy Over Continued HCV Dominance at J P Morgan

Gilead Should Have Investors Giddy Over Continued HCV Dominance at J P Morgan | Hepatitis C New Drugs Review | Scoop.it
January 13, 2016 By Alex Keown, BioSpace.com Breaking News Staff SAN FRANCISCO – While some investor analysts have reported being underwhelmed by some
more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Hepatitis C Virus–Induced Myeloid-Derived Suppressor Cells Suppress NK Cell IFN-γ Production by Altering Cellular Metabolism via Arginase-1

Hepatitis C Virus–Induced Myeloid-Derived Suppressor Cells Suppress NK Cell IFN-γ Production by Altering Cellular Metabolism via Arginase-1 | Hepatitis C New Drugs Review | Scoop.it
Abstract

The hepatitis C virus (HCV) infects ∼200 million people worldwide. The majority of infected individuals develop persistent infection, resulting in chronic inflammation and liver disease, including cirrhosis and hepatocellular carcinoma. The ability of HCV to establish persistent infection is partly due to its ability to evade the immune response through multiple mechanisms, including suppression of NK cells. NK cells control HCV replication during the early phase of infection and regulate the progression to chronic disease. In particular, IFN-γ produced by NK cells limits viral replication in hepatocytes and is important for the initiation of adaptive immune responses. However, NK cell function is significantly impaired in chronic HCV patients. The cellular and molecular mechanisms responsible for impaired NK cell function in HCV infection are not well defined. In this study, we analyzed the interaction of human NK cells with CD33+ PBMCs that were exposed to HCV. We found that NK cells cocultured with HCV-conditioned CD33+ PBMCs produced lower amounts of IFN-γ, with no effect on granzyme B production or cell viability. Importantly, this suppression of NK cell–derived IFN-γ production was mediated by CD33+CD11bloHLA-DRlo myeloid-derived suppressor cells (MDSCs) via an arginase-1–dependent inhibition of mammalian target of rapamycin activation. Suppression of IFN-γ production was reversed by L-arginine supplementation, consistent with increased MDSC arginase-1 activity. These novel results identify the induction of MDSCs in HCV infection as a potent immune evasion strategy that suppresses antiviral NK cell responses, further indicating that blockade of MDSCs may be a potential therapeutic approach to ameliorate chronic viral infections in the liver.

Krishan Maggon 's insight:

Published online before printJanuary 29, 2016, doi:10.4049/jimmunol.1501881The Journal of ImmunologyJanuary 29, 20161501881


Dr. Young S. Hahn, University of Virginia School of Medicine, Beirne Carter Center for Immunology Research, Box 801386, Charlottesville, VA 22904. E-mail address: ysh5e@virginia.edu

more...
No comment yet.
Scooped by Krishan Maggon
Scoop.it!

Merck Takes on Gilead With Sharply Lower Hepatitis C Drug Price

The list price for Merck's (MRK - Get Report) newly approved hepatitis C drug is significantly lower than competing therapies offered by Gilead Sciences (GIL...

more...
No comment yet.