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hepatitis C antiviral

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https://www.readbyqxmd.com/read/28445966/interferon-alpha-antagonizes-the-anti-hepatoma-activity-of-the-oncolytic-virus-m1-by-stimulating-anti-viral-immunity
#1
Liu Ying, Hu Cheng, Xu Wen Xiong, Lin Yuan, Zhang Hai Peng, Zhong Wen Wen, Liang Jian Ka, Xiao Xiao, Cai Jing, Tan Ya Qian, Gao Zhi Liang, Yan Guang Mei, Zhu Wen Bo, Peng Liang
Alpha virus M1 is an oncolytic virus that targets zinc-finger antiviral protein (ZAP)-defective cancer cells, and may be useful for treatment of hepatocellular carcinoma (HCC). Most of HCC patients have hepatitis and need long-term antiviral medication. Thus, it is necessary to clarify whether anti-virus medicines influence oncolytic effect of M1. We examined the effect of drugs used to treat hepatitis B/C on M1-mediated oncolysis in vitro and in vivo. Interferon (IFN)-α induces expression of antiviral IFN-stimulated genes (ISGs) in HCC cells with moderate sensitivity to M1 virus...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445251/long-term-follow-up-of-patients-with-chronic-hepatitis-c-treated-with-%C3%AE-interferon-and-ribavirin-antiviral-therapy-clinical-and-fibrosis-impact-of-treatment-response
#2
Patricia Cordero-Ruiz, Isabel Carmona-Soria, Manuel Rodríguez-Téllez, Angel Caunedo-Alvarez, Roberto H Quezada-Pacheco, Alexander Flores-Cucho, Manuel Romero-Gómez, Ángel Vilches-Arenas
BACKGROUND AND GOALS: The slow progression of chronic hepatitis C (CHC) infection requires long observation periods to detect clinical changes. We compare the incidence of clinical events, hepatocellular carcinoma (HCC), overall mortality, liver-related mortality, and fibrosis progression between patients with a sustained virological response (SVR) and nonresponders (NR) after a 13-year follow-up period. STUDY: One hundred and eighty-two CHC patients, who received interferon and ribavirin treatment between 1996 and 2000, were included...
April 25, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28444868/an-ecological-approach-to-discover-new-bioactive-extracts-and-products-the-case-of-extremophile-plants
#3
Ramla Sahli, Céline Rivière, Christel Neut, Joanne Bero, Marie-Emmanuelle Sahuc, Abderrazak Smaoui, Claire Beaufay, Vincent Roumy, Thierry Hennebelle, Yves Rouillé, Joëlle Quetin-Leclercq, Karin Séron, Riadh Ksouri, Sevser Sahpaz
OBJECTIVES: Eight extremophile plants from Tunisia were screened to find natural products with benefits in human health. METHODS: These plants were collected in different areas in Tunisia. Their methanolic extracts were evaluated for their total phenolic content and for their antiradical (DPPH), antimicrobial (on 35 bacteria and one yeast), antiviral (hepatitis C virus, HCV) and cytotoxic activity (against WI38 and J774 cell lines). The most active species were subjected to a bioguided fractionation...
April 26, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28442915/efficacy-and-safety-outcomes-of-sofosbuvir-based-treatment-regimens-for-hepatitis-c-virus-infected-patients-with-or-without-cirrhosis-from-phase-iii-clinical-trials
#4
REVIEW
Young-Mo Yang, Eun Joo Choi
BACKGROUND: With the appearance of oral direct-acting antivirals (DAAs), the field of hepatitis C virus (HCV) treatment has been dramatically changed. This evolution makes possible for all oral treatments to be available for the treatment of HCV-infected patients. The aims of this review were to report the efficacy and safety of sofosbuvir (SOF)-based regimens for the treatment of patients with chronic HCV infection and to provide our clinical perspectives on these regimens. METHODS: A literature search of clinical studies published in PubMed and posted on ClinicalTrials...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28442624/unphosphorylated-isgf3-drives-constitutive-expression-of-interferon-stimulated-genes-to-protect-against-viral-infections
#5
Wenshi Wang, Yuebang Yin, Lei Xu, Junhong Su, Fen Huang, Yijin Wang, Patrick P C Boor, Kan Chen, Wenhui Wang, Wanlu Cao, Xinying Zhou, Pengyu Liu, Luc J W van der Laan, Jaap Kwekkeboom, Maikel P Peppelenbosch, Qiuwei Pan
Interferon (IFN)-stimulated genes (ISGs) are antiviral effectors that are induced by IFNs through the formation of a tripartite transcription factor ISGF3, which is composed of IRF9 and phosphorylated forms of STAT1 and STAT2. However, we found that IFN-independent ISG expression was detectable in immortalized cell lines, primary intestinal and liver organoids, and liver tissues. The constitutive expression of ISGs was mediated by the unphosphorylated ISGF3 (U-ISGF3) complex, consisting of IRF9 together with unphosphorylated STAT1 and STAT2...
April 25, 2017: Science Signaling
https://www.readbyqxmd.com/read/28442256/functional-evaluation-of-synthetic-flavonoids-and-chalcones-for-potential-antiviral-and-anticancer-properties
#6
Nelly Mateeva, Suresh V K Eyunni, Kinfe K Redda, Ucheze Ononuju, Tony D Hansberry, Cecilia Aikens, Anita Nag
Flavonoids, stilbenes, and chalcones are plant secondary metabolites that often possess diverse biological activities including anti-inflammatory, anti-cancer, and anti-viral activities. The wide range of bioactivities poses a challenge to identify their targets. Here, we studied a set of synthetically generated flavonoids and chalcones to evaluate for their biological activity, and compared similarly substituted flavonoids and chalcones. Substituted chalcones, but not flavonoids, showed inhibition of viral translation without significantly affecting viral replication in cells infected with hepatitis C virus (HCV)...
April 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28440785/impacts-of-hbv-rth55r-polymerase-substitution-on-viral-replication-and-rtm204i-v-resistance-to-nucleoside-nucleotide-antiviral-drugs
#7
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/28440681/discovery-and-preclinical-development-of-dasabuvir-for-the-treatment-of-hepatitis-c-infection
#8
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/28440303/hcv-genotype-6-increased-the-risk-for-hepatocellular-carcinoma-among-asian-patients-with-liver-cirrhosis
#9
Mei-Hsuan Lee, Tiffany I Hsiao, Shreenidhi R Subramaniam, An K Le, Vinh D Vu, Huy N Trinh, Jian Zhang, Mingjuan Jin, Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Mindie H Nguyen
OBJECTIVES: Hepatitis C virus (HCV) infection is a well-documented risk factor for hepatocellular carcinoma (HCC). Seven HCV genotypes have been classified, and the genotypes show a great variety of geographic distribution. HCV genotype 6 is prevalent in Southeast Asia and has been less studied than the other genotypes. METHODS: This follow-up study was designed to evaluate the natural history of HCV genotype 6. The cohort enrolled 851 Asian patients consisting of 222 with HCV genotype 6 and 629 with other genotypes...
April 25, 2017: American Journal of Gastroenterology
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
#10
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
#11
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
#12
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/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
#13
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/28437390/hepatitis-c-positive-kidney-transplant-recipients-when-is-the-best-time-to-treat-with-direct-acting-antiviral-agents
#14
Neeraj Singh, David Dies, Hrishikesh Samant
No abstract text is available yet for this article.
May 2017: Transplantation
https://www.readbyqxmd.com/read/28437385/before-or-after-transplantation-a-review-of-the-cost-effectiveness-of-treating-waitlisted-patients-with-hepatitis-c
#15
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
#16
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/28435690/the-complex-legal-and-ethical-issues-related-to-generic-medications-viral-hepatitis-a-case-study
#17
EDITORIAL
M Danta, N Ghinea
The economic impact of medications is significant, with many countries unable to afford the essential medicines listed by the WHO. Generic medications are one strategy to address this issue. Generic medications are similar to but not the same as originator medications. They have a significant cost advantage because they do not require the background research and development studies to support registration. Consequently, they are gaining increased market share in both the developed and developing world. Many new medications are now licensed to generic manufacturers in the developing world...
April 1, 2017: Journal of Virus Eradication
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
#18
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/28432579/hcv-cure-and-reinfection-among-people-with-hiv-hcv-coinfection-and-people-who-inject-drugs
#19
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
#20
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
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