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
SUMO1 depletion prevents lipid droplet accumulation and HCV replication
TL;DR: To the authors' knowledge, this is the first report showing that SUMO1 regulates lipid droplets in the context of viral infection, and provides a meaningful insight into how HCV replicates and interacts with host proteins.
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Cure of hepatitis C virus infection without interferon alfa: scientific basis and current clinical evidence.
TL;DR: The potency and barrier to resistance of new DAAs and the use of appropriately designed interferon alfa-sparing combinations can overcome obstacles to cure posed by HCV resistance, interferons alfa resistance, and differences in response based on HCV genotype and subtype.
Journal ArticleDOI
Cross-Genotypic Examination of Hepatitis C Virus Polymerase Inhibitors Reveals a Novel Mechanism of Action for Thumb Binders
TL;DR: This study investigates the inhibitory activities of nonnucleoside inhibitors (NNIs) against the HCV RNA-dependent RNA polymerase (RdRp) and highlights a potential differential mode of RdRp inhibition for HCV NNIs, depending on their prospective binding pockets, and demonstrates a surprising enhancement of de novo activity for thumb RdRP binders.
Journal ArticleDOI
Treatment of hepatitis C: perspectives.
Stanislas Pol,M. Corouge +1 more
TL;DR: The combination of second-generation protease inhibitors with PR increased SVR rates from 75 to 90%, while reducing treatment duration, adverse effects, and the number of pills, make any previous publication on hepatitis C treatment obsolete.
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Role of genetic polymorphisms in hepatitis C virus chronic infection.
Nicola Coppola,Mariantonietta Pisaturo,Caterina Sagnelli,Lorenzo Onorato,Evangelista Sagnelli +4 more
TL;DR: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.
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.