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https://www.readbyqxmd.com/read/28432579/hcv-cure-and-reinfection-among-people-with-hiv-hcv-coinfection-and-people-who-inject-drugs
#1
REVIEW
Marianne Martinello, Behzad Hajarizadeh, Jason Grebely, Gregory J Dore, Gail V Matthews
PURPOSE OF REVIEW: Highly effective, well-tolerated interferon-free direct-acting antivirals (DAA) have revolutionised hepatitis C virus (HCV) therapeutics, with the opportunity for broad treatment scale-up among marginalised or "high-risk" populations, including people who inject drugs (PWID) and people with HIV/HCV coinfection. RECENT FINDINGS: Concern that HCV reinfection may compromise HCV treatment outcomes is sometimes cited as a reason for not offering treatment to current and former PWID...
April 21, 2017: Current HIV/AIDS Reports
https://www.readbyqxmd.com/read/28430437/discovery-of-an-hcv-ns5b-replicase-palm-site-allosteric-inhibitor-bms-929075-advanced-to-phase-1-clinical-studies
#2
Kap-Sun Yeung, Brett R Beno, Kyle Parcella, John A Bender, Katherine A Grant-Young, Andrew Nickel, Prashantha Gunaga, Prakash Anjanappa, Rajesh Onkardas Bora, Kumaravel Selvakumar, Karen Rigat, Ying-Kai Wang, Mengping Liu, Julie A Lemm, Kathy Mosure, Steven Sheriff, Changhong Wan, Mark Witmer, Kevin Kish, Umesh M Hanumegowda, Xiaoliang Zhuo, Yue-Zhong Shu, Dawn Parker, Roy Haskell, Alicia Ng, Qi Gao, Elizabeth Colston, Joseph Raybon, Dennis M Grasela, Kenneth S Santone, Min Gao, Nicholas A Meanwell, Michael W Sinz, Matthew G Soars, Jay O Knipe, Susan B Roberts, John F Kadow
The hepatitis C virus NS5B replicase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Inspired by the overlay of bound structures of three structurally distinct NS5B palm site allosteric inhibitors, the high throughput screening hit anthranilic acid 4, the known benzofuran analog 5 and the benzothiadiazine derivative 6, an optimization process utilizing the simple benzofuran template 7 as a starting point for a fragment growing approach was pursued...
April 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28425406/curing-chronic-hepatitis-c-a-cost-comparison-of-the-combination-simeprevir-plus-sofosbuvir-vs-protease-inhibitor-based-triple-therapy
#3
Jacob A Langness, David Tabano, Amanda Wieland, Sarah Tise, Lindsay Pratt, Lauren Ayres Harrington, Sonia Lin, Vahram Ghuschcyan, Kavita V Nair, Gregory T Everson
INTRODUCTION: Interferon-free, multi-direct acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection is highly effective and well tolerated, but costly. To gain perspective on the evolving economics of HCV therapy, we compared the cost per cure of a multi-DAA regimen with the prior standard of triple therapy. MATERIAL AND METHODS: Patients infected with HCV genotype 1 who were treated through the University of Colorado Hepatology Clinic between May 2011 and December 2014 comprised the study population...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28425400/the-direct-acting-antivirals-for-hepatitis-c-virus-and-the-risk-for-hepatocellular-carcinoma
#4
Paulina Chinchilla-López, Xingshun Qi, Eric M Yoshida, Nahum Méndez-Sánchez
The increase of incidences of Hepatocellular Carcinoma (HCC) will continue in the next decades. The therapies about hepatitis C infection has been questioned as a risk factor. Some authors emphasized that sustained virologic response (SVR) with interferon-based therapy reduced the risk of developing HCC. In contrast, some publications that to suggest an increasing risk of HCC in patients treated with Direct-Acting Antivirals (DAA). Whether these therapies are associated with an increased risk of HCC remains to be studied and continued long-term observational studies will be needed...
May 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28424064/effectiveness-of-triple-therapy-with-direct-acting-antivirals-for-hepatitis-c-genotype-1-infection-application-of-propensity-score-matching-in-a-national-hcv-treatment-registry
#5
Emma Gray, David J Pasta, Suzanne Norris, Aisling O'Leary
BACKGROUND: Observational studies are used to measure the effectiveness of an intervention in non-experimental, real world scenarios at the population level and are recognised as an important component of the evidence pyramid. Such data can be accrued through prospective cohort studies and a patient registry is a proven method for this type of study. The national hepatitis C (HCV) registry was established in Ireland in 2012 with the aim of monitoring the clinical and economic outcomes from new, high cost regimens for the treatment of HCV infection...
April 19, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28423231/direct-acting-antiviral-therapy-decreases-hepatocellular-carcinoma-recurrence-rate-in-cirrhotic-patients-with-chronic-hepatitis-c
#6
Victor Virlogeux, Pierre Pradat, Kerstin Hartig-Lavie, François Bailly, Marianne Maynard, Guillaume Ouziel, Domitille Poinsot, Fanny Lebossé, Marie Ecochard, Sylvie Radenne, Samir Benmakhlouf, Joseph Koffi, Philippe Lack, Caroline Scholtes, Anne-Claire Uhres, Christian Ducerf, Jean-Yves Mabrut, Agnès Rode, Massimo Levrero, Christophe Combet, Philippe Merle, Fabien Zoulim
BACKGROUND AND AIMS: Arrival of direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) with high-sustained virological response (SVR) rates and very few side effects has drastically changed the management of HCV infection. The impact of DAA exposure on hepatocellular carcinoma (HCC) recurrence after a first remission in patients with advanced fibrosis remains to be clarified. METHODS: 68 consecutive HCV patients with a first HCC diagnosis and under remission, subsequently treated or not with a DAA combination, were included...
April 19, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28422425/negativization-of-viremia-prior-to-liver-transplant-reduces-early-allograft-dysfunction-in-hepatitis-c-recipients
#7
Silvia Martini, Francesco Tandoi, Lodovico Terzi di Bergamo, Silvia Strona, Bruna Lavezzo, Marco Sacco, Francesca Maione, Federica Gonella, Paolo Strignano, Dominic Dell Olio, Mauro Salizzoni, Giorgio Maria Saracco, Renato Romagnoli
Although early allograft dysfunction (EAD) negatively impacts on survival from the first months following liver transplantation (LT), direct-acting antivirals (DAAs) have revolutionized HCV therapy. We investigated the EAD definition best predicting 90-day graft loss and identified EAD risk factors in HCV positive recipients. From 11-2002 to 06-2016, 603 HCV-positive patients (hepatocellular carcinoma 53.4%) underwent a first LT with HCV-negative donors. Median recipient MELD score 15, median donor age 63 years...
April 19, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/28422376/spontaneous-remission-of-hepatitis-b-virus-reactivation-during-direct-acting-antiviral-agent-based-therapy-for-chronic-hepatitis-c
#8
Ken Sato, Takeshi Kobayashi, Yuichi Yamazaki, Satoshi Takakusagi, Norio Horiguchi, Satoru Kakizaki, Motoyasu Kusano, Masanobu Yamada
The administration of direct-acting antiviral agents (DAAs) to treat hepatitis C virus (HCV) infection has been reported to cause hepatitis B virus (HBV) reactivation. However, the actual conditions of HBV reactivation and the ideal timing of medical intervention have not been fully evaluated. We reported the cases of two female patients dually infected with HBV and HCV. Both patients were inactive HBV carriers. Although the serum HCV RNA levels promptly decreased after the initiation of DAA-based therapy, the serum HBV DNA levels gradually increased during DAA-based therapy, with the peak serum HBV DNA levels observed at 16 weeks after the initiation of DAA-based therapy in both cases...
April 19, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28421422/hepatitis-c-virus-genotype-3-update-on-current-and-emergent-therapeutic-interventions
#9
REVIEW
Steven W Johnson, Dorothea K Thompson, Brianne Raccor
PURPOSE OF REVIEW: Direct-acting antiviral agents (DAAs) have markedly improved the prognosis of hepatitis C virus (HCV)-genotype 3 (GT3), a highly prevalent infection worldwide. However, in patients with hepatic fibrosis, cirrhosis, or hepatocellular carcinoma (HCC), GT3 infection presents a treatment challenge compared with other genotypes. The dependence of the HCV life cycle on host lipid metabolism suggests the possible utility of targeting host cellular factors for combination anti-HCV therapy...
June 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28420944/new-therapies-for-hepatitis-c-virus-infection
#10
Jennifer L Horsley-Silva, Hugo E Vargas
Approximately 350 million people worldwide are infected with hepatitis C virus (HCV), which is associated with morbidity and mortality related to cirrhosis, hepatocellular carcinoma, or liver failure. Recently, vast improvements have been made with the development of direct-acting antiviral (DAA) agents, which are all-oral, are better tolerated than interferon-based treatment, and provide a sustained virologic response in more than 90% of treated patients. This article reviews the new therapies available for HCV infection, with a focus on patients who have chronic HCV with and without compensated cirrhosis...
January 2017: Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28419938/direct-acting-antivirals-the-endgame-for-hepatitis-c
#11
REVIEW
Roberta D'Ambrosio, Elisabetta Degasperi, Massimo Colombo, Alessio Aghemo
Directly-acting antivirals (DAA) have finally allowed all patients to be potentially cured from chronic hepatitis C (HCV) infection. All-oral, Interferon (IFN)-free regimens are based upon the combination of molecules targeting different sites of the HCV replication process. Three classes of DAA exist: protease inhibitors (anti-NS3/4A), RNA-dependent polymerase inhibitors (anti-NS5B) and anti-NS5A inhibitors, which are characterized by different antiviral potency and barrier to resistance and therefore are usually combined in different treatment schedules...
April 15, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28417500/editorial-hepatitis-b-reactivation-in-patients-with-chronic-hepatitis-c-treated-with-direct-acting-antivirals-incidence-severity-of-hepatitis-and-lessons-to-learn
#12
EDITORIAL
https://www.readbyqxmd.com/read/28416549/antiviral-activity-and-resistance-analysis-of-ns3-4a-protease-inhibitor-grazoprevir-and-ns5a-inhibitor-elbasvir-in-hepatitis-c-virus-gt4-replicons
#13
Ernest Asante-Appiah, Stephanie Curry, Patricia McMonagle, Paul Ingravallo, Robert Chase, David Nickle, Ping Qiu, Anita Howe, Frederick C Lahser
Although genotype (GT) 4-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents: grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor, in GT4 replicons prior to clinical studies in this genotype...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28416232/experience-in-real-clinical-practice-with-new-direct-acting-antivirals-in-chronic-hepatitis-c
#14
Fernando Manuel Jiménez-Macías, Manuel Cabanillas-Casafranca, Marta Maraver-Zamora, Gema Romero-Herrera, Federico García-García, Antonio Correia-Varela-Almeida, Ana Cabello-Fernández, Manuel Ramos-Lora
INTRODUCTION AND OBJECTIVE: Inclusion of direct-acting antivirals into clinical practice in patients with chronic HCV (CHC) has been a milestone in medicine. PATIENTS AND METHODS: Analytical, prospective study, involving 126 patients with chronic HCV treated with direct-acting antivirals. Efficacy and safety of treatment and factors associated with failure treatment were evaluated. RESULTS: Age 54±10. Male (70%). Cirrhosis (60%). Distribution according to genotypes: G1a (31%), G1b (42%); G3 (14%); G4 (13%)...
April 14, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28414993/chikungunya-virus-infections-time-to-act-time-to-treat
#15
REVIEW
Rana Abdelnabi, Johan Neyts, Leen Delang
Chikungunya virus (CHIKV) is a re-emerging alphavirus that caused massive outbreaks of Chikungunya fever in several countries and regions in Africa, Asia and more recently in Central and South America. An acute CHIKV infection is usually associated with fever and arthritis and it is rarely fatal. However, 15-60% of patients suffer from chronic polyarthralgia for weeks, months or even for several years after the acute infection. There are currently no vaccines or antivirals available for the prevention or treatment of CHIKV infections...
April 14, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28412293/glecaprevir-and-pibrentasvir-yield-high-response-rates-in-patients-with-hcv-genotype-1-6-without-cirrhosis
#16
Paul Y Kwo, Fred Poordad, Armen Asatryan, Stanley Wang, David L Wyles, Tarek Hassanein, Franco Felizarta, Mark S Sulkowski, Edward Gane, Benedict Maliakkal, J Scott Overcash, Stuart C Gordon, Andrew J Muir, Humberto Aguilar, Kosh Agarwal, Gregory J Dore, Chih-Wei Lin, Ran Liu, Sandra S Lovell, Teresa I Ng, Jens Kort, Federico J Mensa
BACKGROUND: and Aims Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) was evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection. METHODS: SURVEYOR-I and SURVEYOR-II were phase 2, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1-6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin...
April 12, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28411509/direct-acting-antivirals-and-host-targeting-strategies-to-combat-enterovirus-infections
#17
REVIEW
Lisa Bauer, Heyrhyoung Lyoo, Hilde M van der Schaar, Jeroen Rpm Strating, Frank Jm van Kuppeveld
Enteroviruses (e.g., poliovirus, enterovirus-A71, coxsackievirus, enterovirus-D68, rhinovirus) include many human pathogens causative of various mild and more severe diseases, especially in young children. Unfortunately, antiviral drugs to treat enterovirus infections have not been approved yet. Over the past decades, several direct-acting inhibitors have been developed, including capsid binders, which block virus entry, and inhibitors of viral enzymes required for genome replication. Capsid binders and protease inhibitors have been clinically evaluated, but failed due to limited efficacy or toxicity issues...
April 12, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28410351/viral-dynamics-among-hepatitis-c-virus-chronic-infected-patients-during-direct-acting-antiviral-agents-therapy-impact-for-monitoring-and-optimizing-treatment-duration
#18
Andres Tabernilla, Marta Grandal, Berta Pernas, Angeles Castro-Iglesias, Iria Rodríguez-Osorio, Alvaro Mena, Manuel Delgado, Purificacion Cid, Jose D Pedreira, Eva Poveda
OBJECTIVES: Direct-acting antiviral agents (DAAs) have provided an ultimate treatment duration of 12 weeks for most hepatitis C virus (HCV)-infected patients. The opportunity to reduce treatment duration to 6 or 8 weeks is being evaluated. Here, the HCV viral dynamics at short times during HCV therapies and its implications for monitoring and optimizing treatment duration have been assessed. PATIENTS AND METHODS: HCV chronic infected patients who began HCV therapy (March 2014 to June 2015) at a reference hospital of the Northwest of Spain were selected...
April 13, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28409482/efficacy-of-interferon-free-therapies-for-chronic-hepatitis-c-a-systematic-review-of-all-randomized-clinical-trials
#19
REVIEW
Vinicius L Ferreira, Fernanda S Tonin, Nayara A Assis Jarek, Yohanna Ramires, Roberto Pontarolo
BACKGROUND AND OBJECTIVES: Second-generation direct-acting antivirals (DAAs) have recently arisen as more effective and safer treatments for chronic hepatitis C. These drugs can be combined into treatments without interferon (IFN), and are therefore called IFN-free therapies. OBJECTIVE: The objective of this study systematic review was to evaluate the efficacy of IFN-free therapies for the treatment of chronic hepatitis C, and thus increase the clinical evidence for these therapies...
April 13, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28408312/hcv-rna-quantification-in-liver-bioptic-samples-and-extrahepatic-compartments-using-the-abbott-realtime-hcv-assay
#20
Francesco Paolo Antonucci, Valeria Cento, Maria Chiara Sorbo, Matteo Ciancio Manuelli, Ilaria Lenci, Daniele Sforza, Domenico Di Carlo, Martina Milana, Tommaso Maria Manzia, Mario Angelico, Giuseppe Tisone, Carlo Federico Perno, Francesca Ceccherini-Silberstein
BACKGROUND & AIMS: We evaluated the performance of a rapid method to quantify HCV-RNA in the hepatic and extrahepatic compartments, by using for the first time the Abbott RealTime HCV-assay. METHODS: Non-tumoral (NT), tumoral (TT) liver samples, lymph nodes and ascitic fluid from patients undergoing orthotopic-liver-transplantation (N=18) or liver resection (N=4) were used for the HCV-RNA quantification; 5/22 patients were tested after or during direct acting antivirals (DAA) treatment...
April 11, 2017: Journal of Virological Methods
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