Open Access
Nucleotide Polymerase Inhibitor So fos bu vir plus Ribavirin for Hepatitis C
E.J. Gane,Catherine A.M. Stedman,Robert H. Hyland,Xiao Ding,Evguenia S. Svarovskaia,William T. Symonds,R. Hindes,M.M. Berrey +7 more
TLDR
Sofosbuvir plus ribavirin for 12 weeks may be effective in previously untreated patients with HCV genotype 1, 2, or 3 infection, and the rate of sustained virologic response 24 weeks after therapy is reported.Abstract:
BACKGROUND The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated so fos bu vir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection. METHODSread more
Citations
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Journal ArticleDOI
Recent advances and future directions in the management of hepatitis C infections.
TL;DR: Two new agents were approved in late 2013 - sofosbuvir and simeprevir - that have higher barriers to resistance, favorable safety profiles, and profoundly improved success rates; however higher costs associated with the new medications could limit their wider utilization.
Journal ArticleDOI
Sofosbuvir inhibits yellow fever virus in vitro and in patients with acute liver failure.
Erica A. Mendes,Denise Regina Bairros de Pilger,Ana Catharina de Seixas Santos Nastri,Fernanda de Mello Malta,Bruno dos Santos Pascoalino,Luiz Augusto Carneiro D'Albuquerque,Andrea Balan,Lucio Freitas,Edison Luis Durigon,Flair José Carrilho,João Renato Rebello Pinho +10 more
TL;DR: Sofosbuvir may be used as an option for treatment against YFV until other drugs are identified and approved for human use and insights are offered into the role of nonstructural protein 5 (NS5) in YFFV inhibition and suggest that nonStructural proteins may be explored as drug targets for YfV treatment.
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Evolution of a Cell Culture-Derived Genotype 1a Hepatitis C Virus (H77S.2) during Persistent Infection with Chronic Hepatitis in a Chimpanzee
Min Kyung Yi,Fengyu Hu,Michael A. Joyce,Vikas Saxena,Christoph Welsch,Deborah Chavez,Bernadette Guerra,Daisuke Yamane,Ronald L. Veselenak,Richard B. Pyles,Christopher M. Walker,Lorne Tyrrell,Nigel Bourne,Robert E. Lanford,Stanley M. Lemon +14 more
TL;DR: It is demonstrated that a poorly fit virus can replicate for weeks within the liver in the absence of detectable viremia, an observation that expands current concepts of HCV pathogenesis and that is relevant to relapses observed with direct-acting antiviral therapies.
Journal ArticleDOI
Viral and host factors associated with outcomes of hepatitis C virus infection (Review)
Zehui Yan,Yuming Wang +1 more
TL;DR: The present review focused on the identified viral and host factors associated with outcomes of patients with HCV, and assessed the involvement of viral andHost genetics in the natural history and treatment outcomes of HCV infection.
Journal ArticleDOI
Amino acid substitutions in genotype 3a hepatitis C virus polymerase protein affect responses to sofosbuvir
Peter A.C. Wing,Meleri Jones,Michelle Cheung,Sampath DaSilva,Connor G. G. Bamford,Wing-Yiu Jason Lee,Elihu Aranday-Cortes,Ana da Silva Filipe,John McLauchlan,David A. Smith,David A. Smith,William L. Irving,William L. Irving,Morven Cunningham,M. Azim Ansari,M. Azim Ansari,Eleanor Barnes,Eleanor Barnes,Graham R. Foster +18 more
TL;DR: A common polymorphism, V at position 150 in the HCV genotype 3a NS5b polymerase, combined with other variants, reduces the virus response to sofosbuvir and Clinically, infection with HCVgenotype 3 containing this variant reduces odds of sustained virologic response.
References
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Journal ArticleDOI
Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance.
Dongliang Ge,Jacques Fellay,Alexander J. Thompson,Jason Simon,Kevin V. Shianna,Thomas J. Urban,Erin L. Heinzen,Ping Qiu,Arthur H. Bertelsen,Andrew J. Muir,Mark S. Sulkowski,John G. McHutchison,David Goldstein +12 more
TL;DR: It is reported that a genetic polymorphism near the IL28B gene, encoding interferon-λ-3 (IFN-α-2a) is associated with an approximately twofold change in response to treatment, both among patients of European ancestry and African-Americans.
Journal ArticleDOI
Diagnosis, management, and treatment of hepatitis C: An update
TL;DR: This document has been approved by the AASLD, the Infectious Diseases Society of America, and the American College of Gastroenterology.
Journal ArticleDOI
Discovery of a β-d-2'-deoxy-2'-α-fluoro-2'-β-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus.
Michael J. Sofia,Donghui Bao,Wonsuk Chang,Jinfa Du,Dhanapalan Nagarathnam,Rachakonda Suguna,P. Ganapati Reddy,Bruce S. Ross,Peiyuan Wang,Hai-Ren Zhang,Shalini Bansal,Christine Espiritu,Meg Keilman,Angela M. Lam,Holly M. Micolochick Steuer,Congrong Niu,Michael J. Otto,Phillip A. Furman +17 more
TL;DR: Phosphoramidate prodrugs of the 5'-phosphate derivative of the β-d- 2'-deoxy-2'-α-fluoro-2-β-C-methyluridine nucleoside showed significant potency in the HCV subgenomic replicon assay and produced high levels of triphosphates 6 in primary hepatocytes and in the livers of rats, dogs, and monkeys when administered in vivo.
Journal ArticleDOI
Preliminary Study of Two Antiviral Agents for Hepatitis C Genotype 1
Anna S. Lok,David F. Gardiner,Eric Lawitz,Claudia Martorell,Gregory T. Everson,Reem Ghalib,Robert Reindollar,Vinod K. Rustgi,Fiona McPhee,Megan Wind-Rotolo,Anna Persson,Kurt Zhu,Dessislava Dimitrova,Timothy Eley,Tong Guo,Dennis M. Grasela,Claudio Pasquinelli +16 more
TL;DR: This preliminary study involving patients with chronic HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents only.
Journal ArticleDOI
Naturally occurring dominant resistance mutations to hepatitis c virus protease and polymerase inhibitors in treatment-naive patients
Thomas Kuntzen,Joerg Timm,Andrew Berical,Niall Lennon,Aaron M. Berlin,Sarah Young,Bongshin Lee,David Heckerman,Jonathan M. Carlson,Laura L. Reyor,Marianna Kleyman,Cory M. McMahon,Christopher E. Birch,Julian Schulze zur Wiesch,Timothy Ledlie,Michael Koehrsen,Chinnappa D. Kodira,Andrew Roberts,Georg M. Lauer,Hugo R. Rosen,Florian Bihl,Andreas Cerny,Ulrich Spengler,Zhimin Liu,Arthur Y. Kim,Yanming Xing,Arne Schneidewind,Margaret A. Madey,Jaquelyn Fleckenstein,Vicki M. Park,James E. Galagan,Chad Nusbaum,Bruce D. Walker,Bruce D. Walker,Gerond Lake-Bakaar,Eric S. Daar,Ira M. Jacobson,Edward D. Gomperts,Brian R. Edlin,Sharyne M. Donfield,Raymond T. Chung,Andrew H. Talal,Tony N. Marion,Bruce W. Birren,Matthew R. Henn,Todd M. Allen +45 more
TL;DR: Naturally occurring dominant STAT‐C resistance mutations are common in treatment‐naïve patients infected with HCV genotype 1, and their influence on treatment outcome should be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin.