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https://www.readbyqxmd.com/read/28441762/replication-and-oncolytic-activity-of-an-avian-orthoreovirus-in-human-hepatocellular-carcinoma-cells
#1
Robert A Kozak, Larissa Hattin, Mia J Biondi, Juan C Corredor, Scott Walsh, Max Xue-Zhong, Justin Manuel, Ian D McGilvray, Jason Morgenstern, Evan Lusty, Vera Cherepanov, Betty-Anne McBey, David Leishman, Jordan J Feld, Byram Bridle, Éva Nagy
Oncolytic viruses are cancer therapeutics with promising outcomes in pre-clinical and clinical settings. Animal viruses have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. We isolated an avian orthoreovirus (ARV-PB1), and tested it against a panel of hepatocellular carcinoma cells. We found that ARV-PB1 replicated well and induced strong cytopathic effects. It was determined that one mechanism of cell death was through syncytia formation, resulting in apoptosis and induction of interferon stimulated genes (ISGs)...
April 24, 2017: Viruses
https://www.readbyqxmd.com/read/28441362/real-world-experiences-with-the-combination-treatment-of-ledipasvir-plus-sofosbuvir-for-12-weeks-in-hcv-genotype-1-infected-japanese-patients-achievement-of-a-sustained-virological-response-in-previous-users-of-peginterferon-plus-ribavirin-with-hcv-ns3-4a-inhibitors
#2
Tatsuo Kanda, Shin Yasui, Masato Nakamura, Eiichiro Suzuki, Makoto Arai, Yoshihiko Ooka, Sadahisa Ogasawara, Tetsuhiro Chiba, Tomoko Saito, Yuki Haga, Koji Takahashi, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Akinobu Tawada, Hitoshi Maruyama, Fumio Imazeki, Naoya Kato, Osamu Yokosuka
The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98...
April 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28440785/impacts-of-hbv-rth55r-polymerase-substitution-on-viral-replication-and-rtm204i-v-resistance-to-nucleoside-nucleotide-antiviral-drugs
#3
Kuan-Hui Xiang, Cheng-Yu Zhao, Shuai Wang, Yao Li, Ming-Ze Su, Qiang-Yi Wang, Xi-Zhan Xu, Juan Deng, Hui Zhuang, Tong Li
BACKGROUND: High genetic variability at reverse transcriptase (RT) region of hepatitis B virus (HBV) could confer resistance to nucleos(t)ide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUCs resistance. METHODS: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analyzed to identify potential RT substitutions related to NUCs resistance. In vitro studies without and with NUCs were performed in HepG2 cell line transfected by clones with RT harboring wild-type or substituted AA(s) of interest...
April 25, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28440692/both-hepatitis-c-virus-specific-t-cell-responses-and-il28b-rs12979860-single-nucleotide-polymorphism-genotype-influence-antihepatitis-c-virus-treatment-outcome-in-patients-with-chronic-hepatitis-c
#4
José M Benito, Javier García-Samaniego, Marcial García, Antonio Madejón, Luz Martín-Carbonero, Alfonso Cabello, Beatriz Álvarez, Miguel Górgolas, Norma Rallón
Despite new treatments for hepatitis C virus (HCV) infection, IFNα-based regimens still have clinical relevance in special populations of patients and remain the only therapeutic option for many patients. We sought to elucidate the interplay between two relevant factors (IL28B polymorphism and T cell immune responses) involved in the outcome of this therapy in HCV-infected patients. We evaluated 38 patients infected with HCV genotype 1-17 coinfected with HIV-who were undergoing a full course of pegIFNα/RBV therapy...
April 25, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28440681/discovery-and-preclinical-development-of-dasabuvir-for-the-treatment-of-hepatitis-c-infection
#5
Mohamed El Kassas, Tamer Elbaz, Enas Hafez, Mohamed Naguib Wifi, Gamal Esmat
Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality. Positively, the introduction of new directly-acting antivirals (DAAs) have led to dramatic improvements in response rates to antiviral therapy. Furthermore, newer generations of DAAs have demonstrated better safety profiles as well as efficacy than older generations. Current treatment recommendations are based on different combinations of DAAs. Current combination therapies rely on agents that target the different steps of viral replication by using different molecules from various DAAs families...
April 25, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28439936/hiv-positive-men-who-have-sex-with-men-are-at-high-risk-of-development-of-significant-liver-fibrosis-after-an-episode-of-acute-hepatitis-c
#6
K Steininger, A Boyd, S Dupke, I Krznaric, A Carganico, M Munteanu, S Neifer, M Schuetze, M Obermeier, K Arasteh, A Baumgarten, P Ingiliz
Acute hepatitis C virus infection remains a major health concern in human immunodeficiency virus(HIV)-infected men who have sex with men (MSM). New direct-acting antiviral agent (DAA) combination therapy has not yet been approved for the treatment for acute hepatitis C virus(HCV), thereby potentially causing deferral of HCV treatment. Therefore, we aimed to study the course of liver disease after an episode of acute HCV. This study is a retrospective single-centre cohort of HIV-positive MSM with acute HCV infection...
April 25, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28439915/treatment-of-chronic-hepatitis-c-with-direct-acting-antivirals-in-patients-with-%C3%AE-thalassaemia-major-and-advanced-liver-disease
#7
Emmanouil Sinakos, Dimitrios Kountouras, John Koskinas, Kalliopi Zachou, Stylianos Karatapanis, Christos Triantos, Themistoklis Vassiliadis, Ioannis Goulis, Alexandra Kourakli, Efthymia Vlachaki, Barbara Toli, Maria Tampaki, Pinelopi Arvaniti, Georgios Tsiaoussis, Aristea Bellou, Antonis Kattamis, Konstantinos Maragkos, Foteini Petropoulou, George N Dalekos, Evangelos Akriviadis, George V Papatheodoridis
Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with β-thalasaemia major (β-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with β-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439747/management-of-cirrhotic-patients-after-successful-hcv-eradication
#8
REVIEW
Ryan M Kwok, Tram T Tran
Chronic hepatitis C (HCV) is a hepatotropic virus which, when untreated, can lead to progressive inflammation and fibrosis resulting in cirrhosis, hepatocellular carcinoma (HCC), and decompensations related to end-stage liver disease. The relatively recent introduction of all oral, interferon-free, direct-acting antiviral medications against HCV has transformed the management of these patients. Previous treatment regimens were prolonged, poorly tolerated, and frequently did not result in cure. Current therapies achieve sustained viral response (SVR) in the vast majority of patients including those with decompensated liver disease; a previously challenging population to treat...
April 24, 2017: Current Treatment Options in Gastroenterology
https://www.readbyqxmd.com/read/28438089/feline-biliary-tree-and-gallbladder-disease
#9
Corma Ma Otte, Louis C Penning, Jan Rothuizen
Practical relevance Diseases of the biliary tree and gallbladder are more common in cats than diseases of the liver parenchyma. The parenchyma is usually affected secondarily to systemic illnesses, while the biliary system is the prime target for infectious agents (eg, bacteria and flukes) and non-infectious conditions (eg, neoplasia and cysts). Clinical approaches Cats with biliary disease are evaluated because of common feline clinical signs such as anorexia, nausea, vomiting and lethargy. Icterus may or may not be obvious...
May 2017: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/28437794/hepatitis-b-virus-reactivation-associated-with-direct-acting-antiviral-therapy-for-chronic-hepatitis-c-virus-a-review-of-cases-reported-to-the-u-s-food-and-drug-administration-adverse-event-reporting-system
#10
Susan J Bersoff-Matcha, Kelly Cao, Mihaela Jason, Adebola Ajao, S Christopher Jones, Tamra Meyer, Allen Brinker
Background: Direct-acting antiviral agents (DAAs) are used increasingly to treat hepatitis C virus (HCV) infection. Reports were published recently on hepatitis B virus (HBV) reactivation (HBV-R) in patients with HBV-HCV co-infection. Hepatitis B virus reactivation, defined as an abrupt increase in HBV replication in patients with inactive or resolved HBV infection, may result in clinically significant hepatitis. Objective: To assess whether HBV-R is a safety concern in patients receiving HCV DAAs...
April 25, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28437385/before-or-after-transplantation-a-review-of-the-cost-effectiveness-of-treating-waitlisted-patients-with-hepatitis-c
#11
Elliot B Tapper, Nezam H Afdhal, Michael P Curry
All patients with chronic hepatitis C virus (HCV) infections can and should be treated. Though highly effective direct-acting antiviral therapies are costly, the price of a cure is a 1-time investment that is outweighed by future benefits. For clinicians caring for patients requiring liver transplant, the key question relates to the timing of treatment: before or after liver transplantation? On 1 hand, treating HCV often improves our patients' model for end-stage liver disease (MELD) score, decreasing costs, and potentially improving longevity by reducing our patients' risk of death and transplantation...
May 2017: Transplantation
https://www.readbyqxmd.com/read/28437091/speeding-up-early-drug-discovery-in-antiviral-research-a-fragment-based-in-silico-approach-for-the-design-of-virtual-anti-hepatitis-c-leads
#12
Alejandro Speck-Planche, M Natalia Dias Soeiro Cordeiro
Hepatitis C constitutes an unresolved global health problem. This infectious disease is caused by the hepatotropic hepatitis C virus (HCV), and it can lead to the occurrence of life-threatening medical conditions such as cirrhosis and liver cancer. Nowadays, major clinical concerns have arisen due to the appearance of multidrug resistance (MDR), and the side effects especially associated with long-term treatments. In this work, we report the first multitasking model for quantitative structure-biological effect relationships (mtk-QSBER), focused on the simultaneous exploration of anti-HCV activity and in vitro safety profiles related to the absorption, distribution, metabolism, elimination, and toxicity (ADMET)...
April 24, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28435051/akt1-nf%C3%AE%C2%BAb-signaling-pathway-activation-by-a-small-molecule-dma-confers-radioprotection-to-intestinal-epithelium-in-xenograft-model
#13
Vinod Tiwari, Mohammad Zahid Kamran, Atul Ranjan, Hemlata Nimesh, Manish Singh, Vibha Tandon
Normal tissue protection and recovery of radiation-induced damage are of paramount importance for development of radioprotector. Radioprotector which selectively protects normal tissues over cancerous tissues improves the therapeutic window of radiation therapy. In the present study, small bisbenzimidazole molecule, DMA (5-(4-methylpiperazin-1-yl)-2-[2'-(3,4-dimethoxy-phenyl)-5'-benzimidazolyl]-benzimidazole) was evaluated for in vivo radioprotective effects to selectively protect normal tissue over tumor with underlying molecular mechanism...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28434648/nivolumab-in-patients-with-advanced-hepatocellular-carcinoma-checkmate-040-an-open-label-non-comparative-phase-1-2-dose-escalation-and-expansion-trial
#14
Anthony B El-Khoueiry, Bruno Sangro, Thomas Yau, Todd S Crocenzi, Masatoshi Kudo, Chiun Hsu, Tae-You Kim, Su-Pin Choo, Jörg Trojan, Theodore H Welling, Tim Meyer, Yoon-Koo Kang, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Dela Cruz, Lixin Lang, Jaclyn Neely, Hao Tang, Homa B Dastani, Ignacio Melero
BACKGROUND: For patients with advanced hepatocellular carcinoma, sorafenib is the only approved drug worldwide, and outcomes remain poor. We aimed to assess the safety and efficacy of nivolumab, a programmed cell death protein-1 (PD-1) immune checkpoint inhibitor, in patients with advanced hepatocellular carcinoma with or without chronic viral hepatitis. METHODS: We did a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of nivolumab in adults (≥18 years) with histologically confirmed advanced hepatocellular carcinoma with or without hepatitis C or B (HCV or HBV) infection...
April 20, 2017: Lancet
https://www.readbyqxmd.com/read/28434128/aspects-on-the-history-of-transmission-and-favor-of-distribution-of-viruses-by-iatrogenic-action-perhaps-an-example-of-a-paradigm-of-the-worldwide-spread-of-hiv
#15
REVIEW
Lutz G Gürtler, Josef Eberle
Transmission of infectious agents might be associated with iatrogenic actions of charitable help in health care. An example is the vaccination against yellow fever in USA that transmitted hepatitis B virus. Another example is injections of praziquantel for treatment and cure of schistosomiasis in Central and Northern Africa, with a focus in Egypt that has spread hepatitis C virus. There is no indication that human T-lymphotropic virus type 1 was spread by injection treatment for African trypanosomiasis, syphilis and treponematosis, but these treatments might have contributed to the early spread of human immunodeficiency virus type 1 (HIV-1) in Central Africa...
April 22, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28432579/hcv-cure-and-reinfection-among-people-with-hiv-hcv-coinfection-and-people-who-inject-drugs
#16
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
#17
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/28430385/significant-reductions-in-alcohol-use-after-hepatitis-c-treatment-results-from-the-french-anrs-co13-hepavih-cohort
#18
Rod Knight, Perrine Roux, Antoine Vilotitch, Fabienne Marcellin, Eric Rosenthal, Laure Esterle, François Boué, David Rey, Lionel Piroth, Stéphanie Dominguez, Philippe Sogni, Dominique Salmon-Ceron, Bruno Spire, Maria Patrizia Carrieri
BACKGROUND AND AIMS: Few data exist on changes to substance use patterns before and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV co-infected individuals to examine whether receiving Peg-interferon (Peg-IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis and alcohol use. DESIGN: A prospective cohort of HIV-HCV co-infected individuals was enrolled from 2006. Participants' clinical data were retrieved from medical records and socio-demographic and behavioral characteristics were collected by yearly self-administered questionnaires...
April 21, 2017: Addiction
https://www.readbyqxmd.com/read/28429876/iodine-131-meta-iodobenzylguanidine-therapy-for-patients-with-newly-diagnosed-high-risk-neuroblastoma
#19
REVIEW
Kathelijne Cjm Kraal, Elvira C van Dalen, Godelieve Am Tytgat, Berthe Lf Van Eck-Smit
BACKGROUND: Patients with newly diagnosed high-risk (HR) neuroblastoma (NBL) still have a poor outcome, despite multi-modality intensive therapy. This poor outcome necessitates the search for new therapies, such as treatment with (131)I-meta-iodobenzylguanidine ((131)I-MIBG). OBJECTIVES: To assess the efficacy and adverse effects of (131)I-MIBG therapy in patients with newly diagnosed HR NBL. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library 2016, Issue 3), MEDLINE (PubMed) (1945 to 25 April 2016) and Embase (Ovid) (1980 to 25 April 2016)...
April 21, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28428715/impact-of-interferon-free-antivirus-therapy-on-lipid-profiles-in-patients-with-chronic-hepatitis-c-genotype-1b
#20
Daisuke Endo, Kenichi Satoh, Noritomo Shimada, Atsushi Hokari, Yoshio Aizawa
AIM: To investigate the influence of interferon-free antivirus therapy on lipid profiles in chronic hepatitis C virus genotype 1b (HCV1b) infection. METHODS: Interferon-free antiviral agents were used to treat 276 patients with chronic HCV1b infection, and changes in serum lipids of those who achieved sustained virologic response (SVR) were examined. The treatment regimen included 24 wk of daclatasvir plus asunaprevir (DCV + ASV) or 12 wk of sofosbuvir plus ledipasvir (SOF + LDV)...
April 7, 2017: World Journal of Gastroenterology: WJG
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