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Direct antiviral agents

Antonietta Romano, Paolo Angeli, Sara Piovesan, Franco Noventa, Georgios Anastassopoulos, Liliana Chemello, Luisa Cavalletto, Martina Gambato, Francesco Paolo Russo, Patrizia Burra, Valter Vincenzi, Pier Giorgio Scotton, Sandro Panese, Diego Tempesta, Tosca Bertin, Maurizio Carrara, Antonio Carlotto, Franco Capra, Giada Carolo, Giovanna Scroccaro, Alfredo Alberti
BACKGROUND & AIMS: Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of Hepatocellular carcinoma (HCC) during/after therapy with DAAs. Aim of this study was to evaluate incidence of newly diagnosed hepatocellular carcinoma and associated risk factors in patients with advanced hepatitis C treated with DAAs. METHODS: The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in Veneto region (Italy)...
March 15, 2018: Journal of Hepatology
Adel Abdel-Moneim, Alaa Aboud, Mohamed Abdel-Gabbar, Mohamed Zanaty, Mohamed Ramadan
BACKGROUND: The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection. AIMS: To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens...
March 15, 2018: Digestive Diseases and Sciences
Franck Maunoury, Aurore Clément, Chizoba Nwankwo, Laurie Levy-Bachelot, Armand Abergel, Vincent Di Martino, Eric Thervet, Isabelle Durand-Zaleski
OBJECTIVE: To assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment. DESIGN: This study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context...
2018: PloS One
Fei Xiao, Stanley Wang, Rina Barouch-Bentov, Gregory Neveu, Szuyuan Pu, Melanie Beer, Stanford Schor, Sathish Kumar, Vlad Nicolaescu, Brett D Lindenbach, Glenn Randall, Shirit Einav
Hepatitis C virus (HCV) spreads via secreted cell-free particles or direct cell-to-cell transmission. Yet, virus-host determinants governing differential intracellular trafficking of cell-free- and cell-to-cell-transmitted virus remain unknown. The host adaptor proteins (APs) AP-1A, AP-1B, and AP-4 traffic in post-Golgi compartments, and the latter two are implicated in basolateral sorting. We reported that AP-1A mediates HCV trafficking during release, whereas the endocytic adaptor AP-2 mediates entry and assembly...
March 13, 2018: MBio
O El-Sherif, Z G Jiang, E B Tapper, K C Huang, A Zhong, A Osinusi, M Charlton, M Manns, N H Afdhal, K Mukamal, J McHutchison, D M Brainard, N Terrault, M P Curry
BACKGROUND & AIMS: Treatment with direct-acting antiviral (DAA) agents can reduce model for end-stage liver disease and Child-Pugh-Turcotte (CPT) scores in patients with decompensated cirrhosis caused by hepatitis C virus (HCV). However, many of these patients still die or require liver transplantation. We collected data on baseline features of patients and aimed to develop a scoring system to predict response to DAA therapy. METHODS: We performed a retrospective analysis of data from 4 trials of the effects of sofosbuvir-based therapy in patients with HCV-associated decompensated cirrhosis (502 of CPT class B and 120 of CPT class C)...
March 10, 2018: Gastroenterology
Simin Dashti-Khavidaki, Hossein Khalili, Mohsen Nasiri-Toosi
There was no report of nephrotoxicity during clinical trials assessed sofosbuvir for treatment of hepatitis C (HCV) infection. This may be due to excluding patients with severe kidney dysfunction, as a main population at risk for drug-induced nephrotoxicity from these studies. There are some reports of acute kidney injury (AKI) possibly related to sofosbuvir-containing treatments from real-life experiences. Areas covered: Available data on epidemiology, type, and possible risk factors for nephrotoxicity of sofosbuvir-containing treatment are reviewed...
March 14, 2018: Expert Review of Clinical Pharmacology
Giovanni Damiani, Chiara Franchi, Paolo Pigatto, Andrea Altomare, Alessia Pacifico, Stephen Petrou, Sebastiano Leone, Maria Caterina Pace, Marco Fiore
AIM: To evaluate the outcomes in biological treatment and quality of life of psoriatic patients with chronic hepatitis C (CHC) treated with new Direct-Acting Antiviral agents (DAAs) compared to pegylated interferon-2α plus ribavirin (P/R) therapy. METHODS: This is a retrospective study involving psoriatic patients in biological therapy who underwent anti-hepatitis C virus (HCV) treatment at the Department of Dermatology Galeazzi Orthopaedic Institute Milan, Italy from January 2010 to November 2017...
February 27, 2018: World Journal of Hepatology
Satoshi Takakusagi, Ken Sato, Yuhei Suzuki, Yuichi Yamazaki, Takashi Kosone, Satoru Kakizaki, Motoyasu Kusano, Hitoshi Takagi
We herein report a unique case of hepatitis C virus (HCV)-associated renal disease without cryoglobulinemia that showed proteinuria, hypoproteinemia, ascites, and edema. Due to combination therapy with daclatasvir and asunaprevir, the patient achieved sustained virological response at week 24 of the therapy. Furthermore, the therapy caused marked amelioration of her proteinuria, ascites, edema, and hypoalbuminemia, and finally improved her estimated glomerular filtration rate. There were no adverse events, and the combination therapy was well-tolerated...
March 9, 2018: Internal Medicine
Daniel Sauter, Frank Kirchhoff
HIV-1, the main causative agent of AIDS, and related primate lentiviruses show a striking ability to efficiently replicate throughout the lifetime of an infected host. In addition to their high variability, the acquisition of several accessory genes has enabled these viruses to efficiently evade or counteract seemingly strong antiviral immune responses. The respective viral proteins, i.e. Vif, Vpr, Vpu, Vpx and Nef, show a stunning functional diversity, acting by various mechanisms and targeting a large variety of cellular factors involved in innate and adaptive immunity...
February 23, 2018: Cytokine & Growth Factor Reviews
Maria C Sorbo, Valeria Cento, Velia C Di Maio, Anita Y M Howe, Federico Garcia, Carlo F Perno, Francesca Ceccherini-Silberstein
Nowadays, due to the development of potent Direct-Acting Antiviral Agents (DAAs) that specifically target NS3, NS5A and NS5B viral proteins, several new and highly efficacious options to treat chronic Hepatitis C virus (HCV) infection are available. The natural presence of resistance associated substitutions (RASs), as well as their rapid emergence during incomplete drug-pressure, are intrinsic characteristics of HCV that greatly affect treatment outcome and the chances to achieve a virolgical cure. To date, a high number of RASs in NS3, NS5A, and NS5B have been associated in vivo and/or in vitro with reduced susceptibility to DAAs, but no comprehensive RASs list is available...
February 21, 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
O S Nikonov, E S Chernykh, M B Garber, E Yu Nikonova
The genus Enterovirus combines a portion of small (+)ssRNA-containing viruses and is divided into 10 species of true enteroviruses and three species of rhinoviruses. These viruses are causative agents of the widest spectrum of severe and deadly epidemic diseases of higher vertebrates, including humans. Their ubiquitous distribution and high pathogenicity motivate active search to counteract enterovirus infections. There are no sufficiently effective drugs targeted against enteroviral diseases, thus treatment is reduced to supportive and symptomatic measures...
December 2017: Biochemistry. Biokhimii︠a︡
Tatyana Kushner, Douglas Dieterich, Behnam Saberi
PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) affects a significant portion of patients with hepatitis C. The use of direct-acting antiviral (DAA) agents has transformed the disease outcomes in this patient group. RECENT FINDINGS: Hepatitis C virus (HCV) response to DAAs can be affected by the presence of HCC, whereas DAA therapy may affect the risk of HCC recurrence in patients with a history of HCC. SUMMARY: Emerging data are demonstrating lower sustained virologic response (SVR) rates in patients with HCC compared with patients without HCC...
March 6, 2018: Current Opinion in Gastroenterology
Tomohiro Morio, Yuriko Fujita, Satoshi Takahashi
Various antiviral agents have been developed, which are sometimes associated with toxicity, development of virus-resistant strain, and high cost. Virus-specific T-cell (VST) therapy provides an alternative curative therapy that can be effective for a prolonged time without eliciting drug resistance. VSTs can be directly separated using several types of capture devices and can be obtained by stimulating peripheral blood mononuclear cells with viral antigens (virus, protein, or peptide) loaded on antigen-presenting cells (APC)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Lingshu Wang, Wei Shi, James D Chappell, M Gordon Joyce, Yi Zhang, Masaru Kanekiyo, Michelle M Becker, Neeltje van Doremalen, Robert Fischer, Nianshuang Wang, Kizzmekia S Corbett, Misook Choe, Rosemarie D Mason, Joseph G Van Galen, Tongqing Zhou, Kevin O Saunders, Kathleen M Tatti, Lia M Haynes, Peter D Kwong, Kayvon Modjarrad, Wing-Pui Kong, Jason S McLellan, Mark R Denison, Vincent J Munster, John R Mascola, Barney S Graham
Middle East Respiratory Syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or healthcare-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell-cloning strategy, we have identified and characterized multiple neutralizing mAbs specifically binding to the receptor binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques...
March 7, 2018: Journal of Virology
O S Nikonov, M S Nemchinova, V G Klyashtornii, E Yu Nikonova, M B Garber
The currently available structural information is insufficient for a detailed analysis of interactions between human glycyl-tRNA synthetase (GARS) and enterovirus IRESs. At the same time, this information is required in order to understand how this IRES trans-acting factor (ITAF) functions during viral mRNA translation, which is in turn crucial for the development of direct-action antiviral agents. In this paper, a theoretical model of the complex between a cadicivirus A IRES fragment and the anticodon-binding domain of human GARS is constructed using molecular dynamics simulation based on all of the available structural and biochemical data...
January 2018: Molekuliarnaia Biologiia
Stanislas Pol, Olivier Marion, Anaïs Vallet-Pichard, Jean-François Meritet, Karine Sauné, Laurent Alric, Nassim Kamar
BACKGROUND: Direct-acting agents (DAAs) are highly efficient at treating hepatitis C virus (HCV) infections after kidney transplantation. Although drug agencies have recently warned of the risk of hepatitis B virus (HBV) reactivation after patients have received DAAs, reports have discrepant results in HBsAg-positive and HBsAg-negative patients. PATIENTS: We report on three cases of HBV reactivation that were detected after achieving a DAA-associated sustained virological response in three kidney-transplant recipients initially HBsAg-negative...
March 7, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
S Olafsson, T Tyrfingsson, V Runarsdottir, O M Bergmann, I Hansdottir, E S Björnsson, B Johannsson, B Sigurdardottir, R H Fridriksdottir, A Löve, M Hellard, T J Löve, T Gudnason, M Heimisdottir, M Gottfredsson
A nationwide programme for the treatment of all patients infected with hepatitis C virus (HCV) was launched in Iceland in January 2016. By providing universal access to direct-acting antiviral agents to the entire patient population, the two key aims of the project were to (i) offer a cure to patients and thus reduce the long-term sequelae of chronic hepatitis C, and (ii) to reduce domestic incidence of HCV in the population by 80% prior to the WHO goal of HCV elimination by the year 2030. An important part of the programme is that vast majority of cases will be treated within 36 months from the launch of the project, during 2016-2018...
March 7, 2018: Journal of Internal Medicine
Filomena Morisco, Rocco Granata, Silvia Camera, Antonio Ippolito, Michele Milella, Fabio Conti, Chiara Masetti, Antonella Smedile, Paolo Tundo, Teresa Santantonio, Maria Rosa Valvano, Antonio Termite, Pietro Gatti, Vincenzo Messina, Angelo Iacobellis, Marta Librandi, Nicola Caporaso, Angelo Andriulli
Background and aim: Direct antiviral agents (DAAs) have led to high sustained virological responses (SVR) in hepatitis C virus (HCV) patients. However, genotype 3 patients respond to treatment in a suboptimal way. This study aims to identify which of the several treatment schedules recommended for genotype 3 would constitute the best option. Methods: Twenty-four Italian centers were involved in this real-life study of HCV genotype 3 patients treated with DAAs. To expand the number of cases, we conducted a systematic review of the literature on the outcome of genotype 3 patients treated with DAAs...
March 2018: United European Gastroenterology Journal
Salvatore Petta, Luigi Elio Adinolfi, Anna Ludovica Fracanzani, Francesca Rini, Rosalia Caldarella, Vincenza Calvaruso, Calogero Cammà, Marcello Ciaccio, Vito Di Marco, Stefania Grimaudo, Anna Licata, Aldo Marrone, Riccardo Nevola, Rosaria Maria Pipitone, Antonio Pinto, Luca Rinaldi, Daniele Torres, Antonino Tuttolomondo, Luca Valenti, Silvia Fargion, Antonio Craxì
BACKGROUND AND AIM: Recent studies suggest an association between HCV infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive HCV patients with advanced fibrosis or compensated cirrhosis were evaluated by virological, anthropometric and metabolic measurements...
March 2, 2018: Journal of Hepatology
Duraisamy Balaguru
No abstract text is available yet for this article.
March 2018: Southern Medical Journal
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