Journal ArticleDOI
Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options
Ira M. Jacobson,Stuart C. Gordon,Kris V. Kowdley,Eric M. Yoshida,Maribel Rodriguez-Torres,Mark S. Sulkowski,Mitchell L. Shiffman,Eric Lawitz,Gregory T. Everson,Michael J. Bennett,Eugene R. Schiff,M. Tarek Al-Assi,G. Mani Subramanian,Di An,Ming Lin,John McNally,Diana M. Brainard,William T. Symonds,John G. McHutchison,Keyur Patel,Jordan J. Feld,Stephen Pianko,David R. Nelson +22 more
TLDR
In patients with HCV genotype 2 or 3 infection for whom treatment with peginterferon and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbuvir and ribvirin was effective.Abstract:
A B S T R AC T BACKGROUND Patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3 for whom treatment with peginterferon is not an option, or who have not had a response to prior interferon treatment, currently have no approved treatment options. In phase 2 trials, regimens including the oral nucleotide polymerase inhibitor sofosbuvir have shown efficacy in patients with HCV genotype 2 or 3 infection. METHODS We conducted two randomized, phase 3 studies involving patients with chronic HCV genotype 2 or 3 infection. In one trial, patients for whom treatment with peg interferon was not an option received oral sofosbuvir and ribavirin (207 patients) or matching placebo (71) for 12 weeks. In a second trial, patients who had not had a response to prior interferon therapy received sofosbuvir and ribavirin for 12 weeks (103 patients) or 16 weeks (98). The primary end point was a sustained virologic response at 12 weeks after therapy. RESULTS Among patients for whom treatment with peginterferon was not an option, the rate of a sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin, as compared with 0% with placebo (P<0.001). Among previously treated patients, the rate of response was 50% with 12 weeks of treat ment, as compared with 73% with 16 weeks of treatment (difference, −23 percent age points; 95% CI, −35 to −11; P<0.001). In both studies, response rates were lower among patients with genotype 3 infection than among those with genotype 2 infection and, among patients with genotype 3 infection, lower among those with cirrhosis than among those without cirrhosis. The most common adverse events were headache, fatigue, nausea, and insomnia; the overall rate of discontinuation of sofosbuvir was low (1 to 2%). CONCLUSIONS In patients with HCV genotype 2 or 3 infection for whom treatment with peginter feron and ribavirin was not an option, 12 or 16 weeks of treatment with sofosbu vir and ribavirin was effective. Efficacy was increased among patients with HCV genotype 2 infection and those without cirrhosis. In previously treated patients with genotype 3 infection, 16 weeks of therapy was significantly more effective than 12 weeks. (Funded by Gilead Sciences; POSITRON and FUSION ClinicalTrials.gov numbers, NCT01542788 and NCT01604850, respectively.)read more
Citations
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EASL Recommendations on Treatment of Hepatitis C
Jean-Michel Pawlotsky,Alessio Aghemo,Geoffrey Dusheiko,Xavier Forns,Massimo Puoti,Christophe Sarrazin +5 more
TL;DR: The optimal management of patients with acute and chronic HCV infections in 2018 and onwards is described, as well as developments in diagnostic procedures and improvements in therapy and prevention.
Journal ArticleDOI
Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
Nezam H. Afdhal,Stefan Zeuzem,Paul Y. Kwo,Mario Chojkier,Norman Gitlin,Massimo Puoti,Manuel Romero-Gómez,Jean-Pierre Zarski,Kosh Agarwal,Peter Buggisch,Graham R. Foster,Norbert Bräu,Maria Buti,Ira M. Jacobson,G. Mani Subramanian,Xiao Ding,Hongmei Mo,Jenny C. Yang,Phillip S. Pang,William T. Symonds,John G. McHutchison,Andrew J. Muir,Alessandra Mangia,Patrick Marcellin +23 more
TL;DR: Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection.
Journal ArticleDOI
Global Distribution and Prevalence of Hepatitis C Virus Genotypes
Jane P. Messina,Isla Humphreys,Abraham D. Flaxman,Anthony Brown,Graham S Cooke,Oliver G. Pybus,Eleanor Barnes +6 more
TL;DR: It is calculated that HCV genotype 1 is the most prevalent worldwide, comprising 83.4 million cases (46.2% of all HCV cases), approximately one‐third of which are in East Asia.
Journal ArticleDOI
Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus
TL;DR: The goal of the hepatitis C guidance is to provide upto-date recommendations for HCV care practitioners on the optimal screening, management, and treatment for adults with HCV infection in the United States, using a rigorous review process to evaluate the best available evidence.
Journal ArticleDOI
Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection
Mark S. Sulkowski,David F. Gardiner,Maribel Rodriguez-Torres,K. Rajender Reddy,Tarek Hassanein,Ira M. Jacobson,Eric Lawitz,Anna S. Lok,Federico Hinestrosa,Paul J. Thuluvath,Howard J. Schwartz,David R. Nelson,Gregory T. Everson,Timothy Eley,Megan Wind-Rotolo,Shu-Pang Huang,Min Gao,Dennis Hernandez,Fiona McPhee,Diane Sherman,R. Hindes,William T. Symonds,Claudio Pasquinelli,Dennis M. Grasela +23 more
TL;DR: Once-daily oral daclatasvir plus sofosbuvir was associated with high rates of sustained virologic response among patients infected with HCV genotype 1, 2, or 3, including patients with no response to prior therapy with telaprevir or boceprevir.
References
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Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.
Michael W. Fried,Mitchell L. Shiffman,K. Rajender Reddy,C. Smith,George Marinos,Fernando L. Gonçales,Dieter Häussinger,Moisés Diago,Giampiero Carosi,Daniel Dhumeaux,Antonio Craxì,A. Lin,Joseph Hoffman,Jian Yu +13 more
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Interferon Alfa-2b Alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C
John G. McHutchison,Stuart C. Gordon,Eugene R. Schiff,Mitchell L. Shiffman,William M. Lee,Vinod K. Rustgi,Zachary Goodman,Mei Hsiu Ling,Susannah Cort,Janice K. Albrecht +9 more
TL;DR: In patients with chronic hepatitis C, initial therapy withinterferon and ribavirin was more effective than treatment with interferon alone.
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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
Sofosbuvir for previously untreated chronic hepatitis C infection
Eric Lawitz,Alessandra Mangia,David L. Wyles,Maribel Rodriguez-Torres,Tarek Hassanein,Stuart C. Gordon,Michael Schultz,M. Davis,Zeid Kayali,K. Rajender Reddy,Ira M. Jacobson,Kris V. Kowdley,L. Nyberg,G. Mani Subramanian,Robert H. Hyland,Sarah Arterburn,Deyuan Jiang,John McNally,Diana M. Brainard,William T. Symonds,John G. McHutchison,Aasim Sheikh,Zobair M. Younossi,Edward Gane +23 more
TL;DR: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks.
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