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https://www.readbyqxmd.com/read/28530544/the-second-generation-of-highly-potent-hepatitis-c-virus-hcv-ns3-4a-protease-inhibitors-evolutionary-design-based-on-tailor-made-amino-acids-synthesis-and-major-features-of-bio-activity
#1
Shuni Wang, Yibing Wang, Jiang Wang, Tatsunori Sato, Kunisuke Izawa, Vadim A Soloshonok, Hong Liu
Hepatitis C is a current pandemic liver disease caused by the hepatitis C virus (HCV) with high morbidity and mortality. Recently, the direct-acting antiviral agents (DAAs) targeting HCV NS3/4A, NS5A and NS5B have become the most effective therapies against HCV infection in the clinical treatment. Among them, the second-generation of NS3/4A inhibitors have emerged as the mainstay of the DAA therapies, which are derived from the peptide substrate of NS3/4A protease and modified with various tailor-made amino acids in order to achieve high sustained virologic response (SVR) against HCV...
May 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28529212/exploring-the-case-for-eminent-domain-of-hepatitis-c-virus-treatment-patents
#2
T Joseph Mattingly Ii, Emily L Heil, Kathleen S Hoke
Hepatitis C virus (HCV) is a silent epidemic affecting millions of patients and represents the leading indication for liver transplantation in the United States and worldwide. New direct-acting antiviral agents offer the potential to cure patients infected with HCV but it comes at a staggering cost. Given the recent attention to these high-priced HCV therapies and the impact treating individuals with HCV is having on drug expenditures in the United States, there may be a need to revisit drug patent laws and the options the federal government has to ensure patient access to care...
2017: Journal of Health Care for the Poor and Underserved
https://www.readbyqxmd.com/read/28528440/the-human-cmv-ie1-protein-an-offender-of-pml-nuclear-bodies
#3
Myriam Scherer, Eva-Maria Schilling, Thomas Stamminger
PML nuclear bodies (PML-NBs) are SUMOylation-dependent, highly complex protein assemblies that accumulate in the interchromosomal territories of the cell nucleus. Research of the last two decades revealed that many viruses have evolved effector proteins that modify PML-NBs. This correlates with antagonization of individual PML-NB components which act as host cell restriction factors. The multifunctional immediate-early protein IE1 of human cytomegalovirus directly interacts with the PML protein resulting in a disruption of the dot-like structure of PML-NBs...
2017: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/28523927/retinoid-bms411-4-5-5-dimethyl-8-phenyl-5-6-dihydronaphthalen-2-yl-carbonyl-amino-benzoic-acid-a-potential-inhibitor-of-ns5a-protein-of-hepatitis-c-virus-a-candidate-for-combined-therapy-of-hepatitis-c-infection
#4
S Ibrahim, M J Asad, R T Mahmood, F H Wattoo, S Akhter, D Shahwar
Hepatitis C infection is a serious health issue worldwide caused by hepatitis C virus (HCV). There is an urgent need of search for new direct acting antiviral drugs due to the rapid development of drug resistance. The HCV NS5A protein is involved in creating resistance against antiviral therapy and there are also many reports that vitamin A deficiency is associated with non-responsiveness to antiviral treatment in HCV infected patients. So the present in silico study was aimed to find the relation between vitamin A deficiency and the NS5A protein's function in antiviral resistance...
2017: Acta Virologica
https://www.readbyqxmd.com/read/28520728/cost-effectiveness-of-hepatitis-c-treatment-using-generic-direct-acting-antivirals-available-in-india
#5
Rakesh Aggarwal, Qiushi Chen, Amit Goel, Nicole Seguy, Razia Pendse, Turgay Ayer, Jagpreet Chhatwal
BACKGROUND & AIMS: Availability of directly-acting antivirals (DAAs) has changed the treatment landscape of hepatitis C virus (HCV) infection. The high price of DAAs has restricted their use in several countries. However, in some countries such as India, generic DAAs are available at much cheaper price. This study examined whether generic DAAs could be cost-saving and how long it would take for the treatment to become cost-saving/effective. METHODS: A previously-validated, mathematical model was adapted to the HCV-infected population in India to compare the outcomes of no treatment versus treatment with DAAs...
2017: PloS One
https://www.readbyqxmd.com/read/28516201/budget-impact-and-cost-effectiveness-analyses-of-direct-acting-antivirals-for-chronic-hepatitis-c-virus-infection-in-hong-kong
#6
X Li, N S Chan, A W Tam, I F N Hung, E W Chan
The purpose of this investigation was to evaluate the budget impact and cost-effectiveness of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infection in Hong Kong. A decision analytic model was developed to compare short-term costs and health outcomes of patients with chronic HCV genotype 1 infection in Hong Kong who were treated with an interferon (INF)-based treatment (dual therapy of pegylated interferon and ribavirin) or DAA-based treatments (sofosbuvir or ledipasvir/sofosbuvir or ombitasvir/paritaprevir/ritonavir plus dasabuvir)...
May 17, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28513813/hepatitis-b-virus-reactivation-after-effective-sofosbuvir-and-ribavirin-treatment-in-a-patient-with-occult-hepatitis-b-virus-infection
#7
Silvia Odolini, Paola Lanza, Angiola Angiola, Serena Zaltron, Lucia Urbinati, Andrea Vavassori, Paola Nasta, Elena Festa, Franco Gargiulo, Anna Rodella, Arnaldo Caruso, Salvatore Casari, Francesco Castelli, Mauro Viganò
Reactivation of the hepatitis B virus (HBV) has been reported in patients with occult infection (OBI), i.e. HBV surface antigen (HBsAg) negative, HBV core antibody (anti-HBc) positive ± antibodies against HBsAg (anti-HBs) and detectable HBV DNA in serum or liver, receiving immunosuppressive or cytotoxic therapies. Recently, concerns have been raised regarding the risk of HBV reactivation in OBI patients treated with direct acting antiviral agents (DAAs) for chronic hepatitis C (CHC). Here we describe a case of HBV reactivation in a 72-year-old woman with OBI as a possible consequence of effective treatment with sofosbuvir (SOF) and ribavirin (Rbv) for genotype 2a/2c CHC...
May 17, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28512226/reply-to-padmanabhan-and-dixit-hepatitis-c-virus-entry-inhibitors-for-optimally-boosting-direct-acting-antiviral-based-treatments
#8
Hirofumi Ohashi, Yoshiki Koizumi, Kento Fukano, Takaji Wakita, Alan S Perelson, Shingo Iwami, Koichi Watashi
No abstract text is available yet for this article.
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28512091/conformational-flexibility-in-the-immunoglobulin-like-domain-of-the-hepatitis-c-virus-glycoprotein-e2
#9
Ieva Vasiliauskaite, Ania Owsianka, Patrick England, Abdul Ghafoor Khan, Sarah Cole, Dorothea Bankwitz, Steven K H Foung, Thomas Pietschmann, Joseph Marcotrigiano, Felix A Rey, Arvind H Patel, Thomas Krey
The hepatitis C virus (HCV) glycoprotein E2 is the major target of neutralizing antibodies and is therefore highly relevant for vaccine design. Its structure features a central immunoglobulin (Ig)-like β-sandwich that contributes to the binding site for the cellular receptor CD81. We show that a synthetic peptide corresponding to a β-strand of this Ig-like domain forms an α-helix in complex with the anti-E2 antibody DAO5, demonstrating an inside-out flip of hydrophobic residues and a secondary structure change in the composite CD81 binding site...
May 16, 2017: MBio
https://www.readbyqxmd.com/read/28509128/a-case-of-rapid-amelioration-of-hepatitis-c-virus-associated-cryoglobulinemic-membranoproliferative-glomerulonephritis-treated-by-interferon-free-directly-acting-antivirals-for-hcv-in-the-absence-of-immunosuppressant
#10
Fumiaki Obata, Taichi Murakami, Junko Miyagi, Sayo Ueda, Taizo Inagaki, Masanori Minato, Hiroyuki Ono, Kenji Nishimura, Eriko Shibata, Masanori Tamaki, Sakiya Yoshimoto, Fumi Kishi, Seiji Kishi, Motokazu Matsuura, Kojiro Nagai, Hideharu Abe, Toshio Doi
Mixed cryoglobulinemic syndrome, which is a systemic vasculitis characterized by the immune complex deposition in small- and medium-sized arteries and most often due to chronic hepatitis C virus (HCV) infection, sometimes clinically manifests as refractory glomerulonephritis or nephritic syndrome. Patients with mixed cryoglobulinemic nephropathy who have a rapidly progressive glomerulonephritis should receive immunosuppressive therapy. After disease stabilization, patients should receive concurrent therapy for the underlying HCV infection...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28507928/the-role-of-direct-acting-antivirals-in-the-treatment-of-children-with-chronic-hepatitis-c
#11
REVIEW
Christine Hong Ting Yang, Eric R Yoo, Aijaz Ahmed
In the United States, chronic infection with the hepatitis C virus (HCV) affects an estimated 0.1-2% of the pediatric population, who are consequently at risk for major complications, including cirrhosis, hepatocellular carcinoma, and death. The current standard of treatment for chronic hepatitis C (CHC) in children is pegylated-interferon-alpha (PEG-IFN) in combination with ribavirin. PEG-IFN/ribavirin therapy is approved for children ages 3 and older; however, it is often held from use until adulthood because of its extensive list of potential side effects and high likelihood of causing adverse symptoms...
March 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28507926/decrease-of-alpha-fetoprotein-in-patients-with-cirrhosis-treated-with-direct-acting-antivirals
#12
Kelvin Nguyen, Melissa Jimenez, Nima Moghadam, Crystal Wu, Alex Farid, Jonathan Grotts, David Elashoff, Gina Choi, Francisco A Durazo, Mohamed M El-Kabany, Steven-Huy B Han, Sammy Saab
Background and Aims: The lack of specificity has limited the role of serum alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening among patients with cirrhosis related to hepatitis C virus (HCV) infection. We sought to examine whether AFP may decrease after achieving a sustained virological response (SVR) in patients with HCV-related cirrhosis. Methods: We performed a retrospective study of patients with HCV-related cirrhosis who were cured with direct-acting antiviral (DAA) therapy at the University of California, Los Angeles...
March 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28507922/sofosbuvir-use-in-the-setting-of-end-stage-renal-disease-a-single-center-experience
#13
Avin Aggarwal, Eric R Yoo, Ryan B Perumpail, George Cholankeril, Radhika Kumari, Tami J Daugherty, Alex S Lapasaran, Aijaz Ahmed
Background and Aims: Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysis-dependent form a unique group, in which safety, tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further evaluation. Methods: We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based therapy. We evaluated dose escalation to standard-dose SOF in this proof-of-principle experience. Results: Sustained virological response (defined as undetectable viral load at 12 weeks, SVR-12) was achieved in 13 out of the 15 (86...
March 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28507921/sofosbuvir-based-regimens-with-task-shifting-is-cost-effective-in-expanding-hepatitis-c-treatment-access-in-the-united-states
#14
Channa R Jayasekera, Rachel Beckerman, Nathaniel Smith, Ryan B Perumpail, Robert J Wong, Zobair M Younossi, Aijaz Ahmed
Background and Aims: The current paradigm of specialist physician-managed treatment of chronic hepatitis C virus infection (HCV) is inefficient in absorbing the approximately 3 million patients awaiting treatment in the United States. Task shifting-whereby specialist physicians screen patients for treatment eligibility but on-treatment monitoring is devolved to more abundant non-physician clinicians-achieves non-inferior treatment outcomes with second generation direct-acting antivirals (2(nd) Gen DAAs), may increase treatment capacity, and may facilitate greater treatment access...
March 28, 2017: Journal of Clinical and Translational Hepatology
https://www.readbyqxmd.com/read/28507601/end-of-treatment-rna-positive-sustained-viral-response-in-an-individual-with-acute-hepatitis-c-virus-infection-treated-with-direct-acting-antivirals
#15
Eyal Shteyer, Harel Dahari, Ina Gafanovich, Ilana Dery, Dana Wolf, Scott J Cotler, Yoav Lurie
No abstract text is available yet for this article.
May 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#16
Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato, Marcella Visentini
Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of IgM(+)CD27(+) B cells. These cells display both the features of anergy induced by continual engagement of the B cell receptor (BCR), such as high expression of phosphorylated extracellular signal regulated kinase (pERK) and reduced lifespan, and of virus-specific exhaustion such as CD21(low) phenotype and defective response to ligation of BCR and Toll-like receptor 9 (TLR9). Usually MC regresses after eradication of HCV with interferon, whose immunomodulatory activity might contribute to this effect...
May 15, 2017: Blood
https://www.readbyqxmd.com/read/28506435/a-practical-approach-and-model-of-care-for-hcv-treatment-with-direct-acting-antivirals-in-an-urban-setting
#17
Elizabeth Akoth, Chloe Gross, Rachel Silk, Elana Rosenthal, Sarah Kattakuzhy
No abstract text is available yet for this article.
April 26, 2017: Journal of the Association of Nurses in AIDS Care: JANAC
https://www.readbyqxmd.com/read/28506027/final-report-of-unmet-needs-of-interferon-based-therapy-for-chronic-hepatitis-c-in-korea-basis-for-moving-into-the-direct-acting-antiviral-era
#18
Eun Sun Jang, Young Seok Kim, Kyung-Ah Kim, Youn Jae Lee, Woo Jin Chung, In Hee Kim, Byung Seok Lee, Sook-Hyang Jeong
Background/Aims: To evaluate the era of direct acting antivirals (DAAs), we must understand the treatment patterns and outcomes of interferon-based therapy for hepatitis C virus (HCV) infection. We aimed to elucidate the treatment rate, factors affecting treatment decisions, and efficacy of interferon- based therapy in a real-world setting. Methods: This nationwide cohort study included 1,191 newly diagnosed patients with chronic HCV infection at seven tertiary hospitals in South Korea...
May 17, 2017: Gut and Liver
https://www.readbyqxmd.com/read/28504854/the-risk-of-early-occurrence-and-recurrence-of-hepatocellular-carcinoma-in-hepatitis-c-infected-patients-treated-with-direct-acting-antivirals-with-and-without-pegylated-interferon-a-belgian-experience
#19
Bielen Rob, Christophe Moreno, Hans Van Vlierberghe, Stefan Bourgeois, Jean-Pierre Mulkay, Thomas Vanwolleghem, Wim Verlinden, Christian Brixco, Jochen Decaestecker, Chantal De Galocsy, Filip Janssens, Lode Van Overbeke, Christophe Van Steenkiste, Francois D'Heygere, Mike Cool, Katrien Wuyckens, Frederik Nevens, Geert Robaeys
Recently, concerns were raised of high rates of HCC recurrence in patients treated with direct acting antivirals (DAA) for hepatitis C infection. We investigated the HCC occurrence and recurrence rates within six months after treatment with DAA with or without Pegylated Interferon (PEG-IFN) in real life. This is a retrospective, multicenter cohort trial, executed in 15 hospitals distributed across Belgium. Populations were matched based on fibrosis score (Metavir F3-F4). Patients with a Child-Pugh score ≥ B were excluded...
May 15, 2017: Journal of Viral Hepatitis
https://www.readbyqxmd.com/read/28504842/safety-and-efficacy-of-current-daa-regimens-in-kidney-and-liver-transplant-recipients-with-hepatitis-c-results-from-the-hcv-target-study
#20
Varun Saxena, Vandana Khungar, Elizabeth C Verna, Josh Levitsky, Robert S Brown, Mohamed A Hassan, Mark S Sulkowski, Jacqueline G O'Leary, Farrukh Koraishy, Joseph S Galati, Alexander A Kuo, Monika Vainorius, Lucy Akushevich, David R Nelson, Michael W Fried, Norah Terrault, K Rajender Reddy
BACKGROUND: Data outside of clinical trials with direct acting antiviral (DAA) regimens with or without ribavirin as treatment of chronic HCV in solid organ transplant recipients is limited. METHODS: Liver transplant (LT), kidney transplant (KT) and dual liver kidney (DLK) transplant recipients from the HCV-TARGET database, a multicenter, longitudinal clinical care treatment cohort, treated with DAA regimens between January 1 2014 and February 15, 2016 were included to assess safety and efficacy...
May 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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