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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/28522726/draft-genome-sequences-of-bacillus-cereus-e41-and-bacillus-anthracis-f34-isolated-from-algerian-salt-lakes
#2
Mohamed Seghir Daas, Albert Remus R Rosana, Jeella Z Acedo, Farida Nateche, Salima Kebbouche-Gana, John C Vederas, Rebecca J Case
Two strains of Bacillus, B. cereus E41 and B. anthracis F34, were isolated from a salt lake in Aïn M'lila-Oum El Bouaghi, eastern Algeria, and Ain Baida-Ouargla, southern Algeria, respectively. Their genomes display genes for the production of several bioactive secondary metabolites, including polyhydroxyalkanoate, iron siderophores, lipopeptides, and bacteriocins.
May 18, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28521816/biochemical-characterization-of-the-xylan-hydrolysis-profile-of-the-extracellular-endo-xylanase-from-geobacillus-thermodenitrificans-t12
#3
Martinus J A Daas, Patricia Murciano Martínez, Antonius H P van de Weijer, John van der Oost, Willem M de Vos, Mirjam A Kabel, Richard van Kranenburg
BACKGROUND: Endo-xylanases are essential in degrading hemicellulose of various lignocellulosic substrates. Hemicellulose degradation by Geobacillus spp. is facilitated by the hemicellulose utilization (HUS) locus that is present in most strains belonging to this genus. As part of the HUS locus, the xynA gene encoding an extracellular endo-xylanase is one of the few secreted enzymes and considered to be the key enzyme to initiate hemicellulose degradation. Several Geobacillus endo-xylanases have been characterized for their optimum temperature, optimum pH and generation of degradation products...
May 18, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28520749/access-and-response-to-direct-antiviral-agents-daa-in-hiv-hcv-co-infected-patients-in-italy-data-from-the-icona-cohort
#4
Antonella d'Arminio Monforte, Alessandro Cozzi-Lepri, Francesca Ceccherini-Silberstein, Andrea De Luca, Sergio Lo Caputo, Antonella Castagna, Cristina Mussini, Antonella Cingolani, Alessandro Tavelli, Milensu Shanyinde, Andrea Gori, Enrico Girardi, Massimo Andreoni, Andrea Antinori, Massimo Puoti
BACKGROUND: Real-life data on access and response to direct antiviral agents (DAA) in HIV-HCV coinfected individuals are lacking. METHODS: HCV viremic, HIV-positive patients from Icona and Hepaicona cohorts naïve to DAA by January 2013 were included. Access and predictors of starting DAA were evaluated. Switches of antiretroviral drugs at starting DAA were described. We calculated sustained virological response (SVR12) in those reaching 12 weeks after end-of-treatment (EOT), and defined treatment failure (TF) as discontinuation of DAA before EOT or non-SVR12...
2017: PloS One
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/28512420/a-case-of-iris-melanocytoma-demonstrating-diffuse-melanocytic-proliferation-with-uncontrolled-intraocular-pressure
#8
Mami Kusunose, Yuji Sakino, Yoshihiro Noda, Tsutomu Daa, Toshiaki Kubota
We report a rare case with histologically proven melanocytoma of the iris that demonstrated diffuse melanocytic proliferation with uncontrolled secondary glaucoma and investigate the etiology of the intraocular pressure elevation. The patient was a 78-year-old man with a history of darkened iris of his left eye. The intraocular pressure was 39 mm Hg. A slit-lamp examination showed a diffuse darkened iris, and a gonioscopic examination revealed open angle with circumferential heavy pigmentation. There was no pigment dispersion of the anterior chamber and no pigment deposition of the cornea...
January 2017: Case Reports in Ophthalmology
https://www.readbyqxmd.com/read/28511947/intraoperative-femur-fracture-risk-during-primary-direct-anterior-approach-cementless-total-hip-arthroplasty-with-and-without-a-fracture-table
#9
Eric M Cohen, Joshua J Vaughn, Scott A Ritterman, Daniel L Eisenson, Lee E Rubin
BACKGROUND: There is no study to date comparing intraoperative femur fractures (IFFs) in the direct anterior approach (DAA) with and without a fracture table. We hypothesize that there is no significant difference in the IFF with and without a fracture table when performed by experienced DAA hip surgeons. METHODS: This study is a 1-year retrospective review of patients who underwent DAA total hip arthroplasty by 2 surgeons: one surgeon uses a flat table and manually elevates the femur with a large bone hook, while the other surgeon uses a fracture table and a mechanical femoral elevator...
April 21, 2017: Journal of Arthroplasty
https://www.readbyqxmd.com/read/28509328/anatomy-based-dmek-wetlab-in-homburg-saar-novel-aspects-of-donor-preparation-and-host-maneuvers-to-teach-descemet-membrane-endothelial-keratoplasty
#10
B Seitz, L Daas, M Bischoff-Jung, N Szentmáry, S Suffo, M El-Husseiny, A Viestenz, G Milioti
INTRODUCTION: Use of Descemet Membrane Endothelial Keratoplasty (DMEK) has been limited because of problems with donor preparation, i.e. tearing of the Descemet membrane and difficulties in unfolding the Endothelium-Descemet-Membrane-Layer (EDML) in the anterior chamber (AC). The purpose of this work was to describe a novel approach to teaching anatomy-based donor and recipient preparation in a DMEK-Wetlab. MATERIAL AND METHODS: We teach successful mono-manual donor preparation of human corneas in organ culture not suitable for transplantation, including peripheral markers for orientation...
May 16, 2017: Clinical Anatomy
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
#11
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/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/28507081/reversion-of-anergy-signatures-in-clonal-cd21low-b-cells-of-mixed-cryoglobulinemia-after-clearance-of-hcv-viremia
#15
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/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
#16
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
#17
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
#18
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
https://www.readbyqxmd.com/read/28500586/evidence-of-spontaneous-post-transplant-hcv-eradication-in-two-failed-daa-treatments-awaiting-liver-transplantation
#19
Ilaria Lenci, Alessandra Bosa, Martina Milana, Leonardo Baiocchi, Francesco Paolo Antonucci, Marianna Aragri, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Giuseppe Tisone, Mario Angelico
No abstract text is available yet for this article.
May 12, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28499845/exploring-resistance-pathways-for-first-generation-ns3-4a-protease-inhibitors-boceprevir-and-telaprevir-using-bayesian-network-learning
#20
Lize Cuypers, Pieter Libin, Yoeri Schrooten, Kristof Theys, Velia Chiara Di Maio, Valeria Cento, Maja M Lunar, Frederik Nevens, Mario Poljak, Francesca Ceccherini-Silberstein, Ann Nowé, Kristel Van Laethem, Anne-Mieke Vandamme
Resistance-associated variants (RAVs) have been shown to influence treatment response to direct-acting antivirals (DAAs) and first generation NS3/4A protease inhibitors (PIs) in particular. Interpretation of hepatitis C virus (HCV) genotypic drug resistance remains a challenge, especially in patients who previously failed DAA therapy and need to be retreated with a second DAA based regimen. Bayesian network (BN) learning on HCV sequence data from patients treated with DAAs could provide insight in resistance pathways against PIs for HCV subtypes 1a and 1b, in a similar way as applied before for HIV...
May 9, 2017: Infection, Genetics and Evolution
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