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https://www.readbyqxmd.com/read/28820725/understanding-hepatitis-c-virus-drug-resistance-clinical-implications-for-current-and-future-regimens
#1
David L Wyles, Anne F Luetkemeyer
Viral resistance to direct-acting antiviral drugs may impact their effectiveness during treatment of hepatitis C virus (HCV) infection. Most data on HCV drug resistance concern genotypes 1 and 3. The clinical impact of resistance to HCV nonstructural protein 5A (NS5A) inhibitors and a practical approach to indications and methods for resistance testing are discussed.
July 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28820612/the-potential-of-signal-peptide-peptidase-as-a-therapeutic-target-for-hepatitis-c
#2
Kohji Moriishi
Chronic infection with hepatitis C virus (HCV) causes liver steatosis, cirrhosis, metabolic syndrome with inflammation, and eventually leads to hepatocellular carcinoma. HCV core protein is a well-known capsid protein and pathogenic factor related to lipid accumulation, type 2 diabetes mellitus, and carcinogenesis. Cleavage of the C-terminal transmembrane region by signal peptide peptidase (SPP) is required for maturation of the core protein. Areas covered: Herein, this review details the general aspects of the structure, lifecycle, pathogenesis, and maturation of the HCV core protein, the function of SPP, and clinically available direct-acting antivirals (DAAs)...
August 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28819570/hcv-integrated-care-a-randomized-trial-to-increase-treatment-initiation-and-svr-with-direct-acting-antivirals
#3
Erik J Groessl, Lin Liu, Marisa Sklar, Samuel B Ho
BACKGROUND AND AIMS: Psychiatric or substance use disorders are barriers to successful HCV antiviral treatment. In a randomized, controlled trial (RCT), the effects of HCV Integrated Care (IC) for increasing treatment rates and sustained viral response (SVR) were studied with direct acting antivirals (DAA). METHODS: In 2012-13, VA patients, whose screening was positive for depression, PTSD, or substance use (N = 79), were randomized to IC or Usual Care (UC). IC consisted of brief psychological interventions and case management...
2017: International Journal of Hepatology
https://www.readbyqxmd.com/read/28818546/glecaprevir-plus-pibrentasvir-for-chronic-hepatitis-c-virus-genotype-1-2-4-5-or-6-infection-in-adults-with-compensated-cirrhosis-expedition-1-a-single-arm-open-label-multicentre-phase-3-trial
#4
Xavier Forns, Samuel S Lee, Joaquin Valdes, Sabela Lens, Reem Ghalib, Humberto Aguilar, Franco Felizarta, Tarek Hassanein, Holger Hinrichsen, Diego Rincon, Rosa Morillas, Stefan Zeuzem, Yves Horsmans, David R Nelson, Yao Yu, Preethi Krishnan, Chih-Wei Lin, Jens J Kort, Federico J Mensa
BACKGROUND: The once-daily, ribavirin-free, pangenotypic, direct-acting antiviral regimen, glecaprevir coformulated with pibrentasvir, has shown high rates of sustained virological response in phase 2 and 3 studies. We aimed to assess the efficacy and safety of 12 weeks of coformulated glecaprevir and pibrentasvir in patients with hepatitis C virus (HCV) infection and compensated cirrhosis. METHODS: We did this single-arm, open-label, multicentre phase 3 study at 40 sites in Belgium, Canada, Germany, South Africa, Spain, and the USA...
August 14, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/28815296/autoantibodies-against-rods-and-rings-related-impdh2-in-hepatitis-c-genotype-1-and-daa-therapy-in-a-real-life-cohort
#5
Werner Dammermann, Susanne Polywka, Inga Dettmann, Swantje Mindorf, Lars Komorowski, Malte Wehmeyer, Julian Schulze Zur Wiesch, Winfried Stöcker, Stefan Lüth
Autoantibodies against inosine-5'-monophosphate-dehydrogenase-2 (IMPDH2; "rods and rings" pattern) develop in chronic hepatitis C (CHC) patients under treatment with peg-interferon (IFN) and ribavirin (RBV), an inhibitor of IMPDH2. We investigated the influence of the alternative therapy with direct-acting antivirals (DAA)/ribavirin on anti-IMPDH2 autoantibody generation and the use of anti-IMPDH2 development as a marker for therapy outcome (sustained virologic response, SVR). We analyzed a "real life" cohort of 104 unselected CHC genotype 1 (GT1) patients treated with IFN/first-generation DAA/RBV prospectively compared to a historic cohort of 59 IFN/RBV-treated CHC GT1 patients...
August 16, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28815028/the-majority-of-hepatitis-c-patients-treated-with-direct-acting-antivirals-are-at-risk-for-relevant-drug-drug-interactions
#6
Elise J Smolders, Floor Ac Berden, Clara Tmm de Kanter, Wietske Kievit, Joost Ph Drenth, David M Burger
BACKGROUND: Direct-acting antivirals have improved treatment of chronic hepatitis C virus infection significantly. Direct-acting antivirals inhibit/induce and can also be substrates of drug-metabolising enzymes and transporters. This increases the risk for drug-drug interactions. OBJECTIVE: The purpose of this study was to predict drug-drug interactions with co-medication used by hepatitis C virus-infected patients. METHODS: We assembled a nationwide cohort of hepatitis C patients and collected cross-sectional data on co-medication use...
August 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28814517/zinc-salts-block-hepatitis-e-virus-replication-by-inhibiting-the-activity-of-viral-rna-dependent-rna-polymerase
#7
Nidhi Kaushik, Chandru Subramani, Saumya Anang, Rajagopalan Muthumohan, Shalimar, Baibaswata Nayak, C T Ranjith-Kumar, Milan Surjit
Hepatitis E virus (HEV) causes an acute, self limiting hepatitis in normal individuals and leads to chronic disease in immunocompromised individuals. HEV infection in pregnant women results in a more severe outcome, with the mortality rate going upto 30%. Though the virus usually causes sporadic infection, epidemics have been reported in developing and resource starved countries. No specific anti-viral exists against HEV. A combination of interferon and ribavirin therapy has been used to control the disease with some success...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28812869/entry-inhibitors-a-perspective-for-prevention-of-hepatitis-c-virus-infection-in-organ-transplantation
#8
Che C Colpitts, Raymond T Chung, Thomas F Baumert
Entry inhibitors are emerging as an attractive class of therapeutics for hepatitis C virus (HCV) infection. Entry inhibitors target either virion-associated factors or cellular factors necessary for infection. By blocking entry into cells, entry inhibitors prevent both the establishment of persistent reservoirs and the emergence of resistant variants during viral replication. Furthermore, entry inhibitors protect naïve cells from virus-induced alterations. Combining entry inhibitors with direct-acting antivirals (DAAs) may therefore improve treatment outcomes, particularly in the context of organ transplantation...
August 16, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28811242/natural-ns5a-inhibitor-resistance-associated-substitutions-in-hcv-genotype-1-infected-patients-from-italy
#9
Cinzia Caudai, Angelo Materazzi, Francesco Saladini, Simona Di Gianbenedetto, Carlo Torti, Barbara Ricciardi, Barbara Rossetti, Paolo Almi, Andrea De Luca, Maurizio Zazzi
OBJECTIVES: Genetic variability in NS5A is associated to different levels of resistance to the currently licensed NS5A inhibitors. The aim of this study was to detect NS5A inhibitor resistance associated substitutions (RASs) in HCV genotype 1 (GT1) patients naïve to direct acting HCV antivirals. METHODS: Amplification, Sanger sequencing and phylogenetic analysis of the HCV NS5A region were performed on plasma obtained from 122 consecutive patients with HCV chronic infection attending four different clinics in Italy...
August 12, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28811159/implementing-and-scaling-up-hcv-treatment-services-for-people-who-inject-drugs-and-other-high-risk-groups-in-ukraine-an-evaluation-of-programmatic-and-treatment-outcomes
#10
Alyona Mazhnaya, Anna Meteliuk, Tetiana Barnard, Alexei Zelenev, Sergii Filippovych, Frederick L Alticec
BACKGROUND: HCV prevalence estimates among people who inject drugs (PWID) in Ukraine is high (60-90%), yet barriers to HCV treatment and care remain substantial including limited access to direct acting antiviral (DAA) medications. A feasibility scale-up project implemented HCV treatment in community-based settings to improve access to DAA treatment for key populations in this context. METHODS: Using program-level data and verified medical records, we describe the development, implementation processes and outcomes for HCV treatment for PWID and other risks groups...
August 12, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28811158/high-hcv-cure-rates-for-people-who-use-drugs-treated-with-direct-acting-antiviral-therapy-at-an-urban-primary-care-clinic
#11
Brianna L Norton, Julia Fleming, Marcus A Bachhuber, Meredith Steinman, Joseph DeLuca, Chinazo O Cunningham, Nirah Johnson, Fabienne Laraque, Alain H Litwin
BACKGROUND: Though direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear. METHODS: We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n=89) at a primary care clinic in the Bronx, NY...
August 12, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28809742/treatment-of-chronic-hcv-infection-with-the-new-direct-acting-antivirals-daa-first-report-of-a-real-world-experience-in-southern-brazil
#12
Hugo Cheinquer, Hoel Sette-Jr, Fernando H Wolff, Alexandre de Araujo, Silvia Coelho-Borges, Silvia R P Soares, Mauricio F A Barros
INTRODUCTION AND AIM: There is almost no data regarding the efficacy of direct acting antivirals (DAAs) therapy in Brazil. The aim of this historical cohort study is to describe the sustained virologic response (SVR) rate among real-world compensated chronic hepatitis C patients in three hepatology centers from Southern Brazil. MATERIALS AND METHODS: Patients were included if they had at least 12 weeks follow-up after the end of therapy. Patients that were lost to follow-up or had treatment prematurely interrupted for any reason were considered treatment failure in this intention to treat analysis...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28809741/hepatitis-c-virus-infection-outcomes-among-immigrants-to-canada-a-retrospective-cohort-analysis
#13
Curtis L Cooper, Kednapa Thavorn, Ecaterina Damian, Daniel J Corsi
INTRODUCTION AND AIM: HCV-infected immigrants contribute to the total prevalence in Canada and other developed nations. Little is known about engagement in care, access to service, and treatment outcomes in recipients of Direct Acting Antiviral (DAA) HCV therapies among immigrants living with HCV. MATERIAL AND METHODS: HCV patients assessed at The Ottawa Hospital Viral Hepatitis Clinic between 2000-2016 were identified. Immigration history, race, socioeconomic status, HCV work-up, treatment and outcome data were evaluated...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28809740/early-successes-in-an-open-access-provincially-funded-hepatitis-c-treatment-program-in-prince-edward-island
#14
Daniel Smyth, Jordan W Francheville, Robin Rankin, Jeremy Beck, Connie Hoare, Stefanie Materniak, Greg German, Lisa Barrett, Natalie Bunimov-Wall
INTRODUCTION: The availability of curative hepatitis C therapies has created an opportunity to improve delivery and access. Local providers, government, industry, and community groups in Prince Edward Island developed an innovative province-wide care model. Our goal was to describe the first year of program implementation. MATERIAL AND METHODS: Using a community based prospective observational study design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28809730/transplanting-kidney-allografts-from-hepatitis-c-infected-donors-into-hepatitis-c-uninfected-recipients-re-thinking-the-thinker-trial
#15
Eric M Yoshida, Trana Hussaini
In the not so distant past, organs from hepatitis C infected donors were either discarded or rarely transplanted into HCV viremic recipients - but never allocated to non-infected patients. However, the simplicity, ease and unprecedented success rates of HCV direct acting antiviral regimens has raised the possibility of utilizing such organs in an attempt to expand the donor pool. The thinker trial reports the first of such attempts. However, caution must be exercised prior to the widespread adoption of such strategy...
August 8, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28805329/editorial-good-news-to-patients-with-thalassaemia-hcv-clearance-made-easy-with-direct-acting-antivirals
#16
EDITORIAL
R D'Ambrosio, P Lampertico
No abstract text is available yet for this article.
September 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28805326/editorial-good-news-to-patients-with-thalassaemia-hcv-clearance-made-easy-with-direct-acting-antivirals-authors-reply
#17
EDITORIAL
A Mangia, V Piazzolla, R Santoro
No abstract text is available yet for this article.
September 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28804248/effect-of-chronic-hepatitis-c-virus-treatment-by-combination-therapy-on-cardiovascular-system
#18
Reda Biomy, Mohamed Abdelshafy, Ahmed Abdelmonem, Hesham Abu-Elenin, George Ghaly
BACKGROUND: The prevalence of hepatitis C virus (HCV) in Egypt is quite high, and the combined oral direct-acting antiviral agents (DAAs) may have impressive results. OBJECTIVE: To assess the cardiovascular effects of DAAs in patients with HCV. METHODS: A total of 170 patients with HCV were divided into 2 groups: first group (100 patients) received triple combination therapy (pegylated interferon alfa, sofosbuvir, and ribavirin, whereas the second group (70 patients) received dual combination therapy (sofosbuvir and simeprevir)...
2017: Clinical Medicine Insights. Cardiology
https://www.readbyqxmd.com/read/28802876/hepatocellular-carcinoma-risk-following-direct-acting-antiviral-hcv-therapy-a-systematic-review-meta-analyses-and-meta-regression
#19
Reem Waziry, Behzad Hajarizadeh, Jason Grebely, Janaki Amin, Matthew Law, Mark Danta, Jacob George, Gregory J Dore
BACKGROUND: Risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) HCV therapy remains unclear. The aims of this study were: 1) In patients with HCV-related cirrhosis, to compare the rate of HCC occurrence following DAA versus interferon (IFN)-based cure, and; 2) In patients who received curative HCC treatment, to compare rate of HCC recurrence following DAA versus IFN-based cure. METHODS: A search was conducted for reports published between January 2000 and February 2017...
August 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28802816/safety-and-efficacy-of-an-8-week-regimen-of-grazoprevir-plus-ruzasvir-plus-uprifosbuvir-compared-with-grazoprevir-plus-elbasvir-plus-uprifosbuvir-in-participants-without-cirrhosis-infected-with-hepatitis-c-virus-genotypes-1-2-or-3-c-crest-1-and-c-crest-2-part
#20
Edward J Gane, Stephen Pianko, Stuart K Roberts, Alexander J Thompson, Stefan Zeuzem, Eli Zuckerman, Ziv Ben-Ari, Graham R Foster, Kosh Agarwal, Alex L Laursen, Jan Gerstoft, Wei Gao, Hsueh-Cheng Huang, Brian Fitzgerald, Doreen Fernsler, Jerry J Li, Anjana Grandhi, Hong Liu, Feng-Hsiu Su, Shuyan Wan, Zhen Zeng, Huei-Ling Chen, Frank J Dutko, Bach-Yen T Nguyen, Janice Wahl, Michael N Robertson, Eliav Barr, Wendy W Yeh, Rebeca M Plank, Joan R Butterton, Rafael Esteban
BACKGROUND: New hepatitis C virus (HCV) therapies with pan-genotypic efficacy are needed. The goals of part A of C-CREST-1 and C-CREST-2 were to compare the efficacies of two doses (300 mg or 450 mg once daily) of uprifosbuvir (MK-3682; NS5B inhibitor) in an 8-week regimen combined with grazoprevir (NS3/4A inhibitor; 100 mg once daily) and an NS5A inhibitor, either elbasvir (50 mg once daily) or ruzasvir (MK-8408; 60 mg once daily), and to evaluate the safety and tolerability of these combination regimens in individuals infected with genotypes 1, 2, or 3...
August 9, 2017: Lancet. Gastroenterology & Hepatology
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