OBJECTIVES: Patients with chronic hepatitis C virus (HCV) and cirrhosis are in critical need of treatment that is both effective and tolerable. The combination of simeprevir (SMV), a protease inhibitor, and sofosbuvir (SOF), a polymerase inhibitor, without peginterferon and/or ribavirin (PEGINF/RBV) has been shown to achieve sustained virologic response (SVR) exceeding 90% in patients with HCV genotype 1 with prior nonresponse and/or cirrhosis. The present report describes the efficacy of SMV and SOF in patients with cirrhosis, prior or current hepatic decompensation, and other contraindications to PEGINF/RBV. METHODS: A total of 120 consecutive patients with cirrhosis and contraindications to PEGINF/RBV were treated with SMV and SOF for 12 weeks. The primary end point was SVR at 12 weeks after the completion of treatment. RESULTS: The mean age of the cohort was 60 years; 63% were male, 48% were Caucasian, 44% were African American, 69% were of genotype 1A, 49% were treatment naïve, 96% were interleukin-28B non-CC, 33% were of Child class B or C, and 25% had prior hepatic decompensation. The SVR by intention-to-treat was 81% with a relapse rate of 14%. The SVR by per-protocol analysis was 87% with a relapse rate of 13%. The only baseline factor associated with SVR by multifactor analysis was Child class. SVR in patients with Child class A, B, and C was 87, 77, and 67%, respectively. Eleven percent of the patients developed severe adverse events, which included sepsis (two), variceal bleeding (two), hepatocellular carcinoma (two), and hyperbilirubinemia (eight). One of the patients with sepsis died. Two patients developed relapse more than 12 weeks after stopping SMV and SOF. CONCLUSIONS: The combination of SMV and SOF achieves high rates of SVR in patients with advanced cirrhosis but is lower with worsening Child class.
OBJECTIVES:Patients with chronic hepatitis C virus (HCV) and cirrhosis are in critical need of treatment that is both effective and tolerable. The combination of simeprevir (SMV), a protease inhibitor, and sofosbuvir (SOF), a polymerase inhibitor, without peginterferon and/or ribavirin (PEGINF/RBV) has been shown to achieve sustained virologic response (SVR) exceeding 90% in patients with HCV genotype 1 with prior nonresponse and/or cirrhosis. The present report describes the efficacy of SMV and SOF in patients with cirrhosis, prior or current hepatic decompensation, and other contraindications to PEGINF/RBV. METHODS: A total of 120 consecutive patients with cirrhosis and contraindications to PEGINF/RBV were treated with SMV and SOF for 12 weeks. The primary end point was SVR at 12 weeks after the completion of treatment. RESULTS: The mean age of the cohort was 60 years; 63% were male, 48% were Caucasian, 44% were African American, 69% were of genotype 1A, 49% were treatment naïve, 96% were interleukin-28B non-CC, 33% were of Child class B or C, and 25% had prior hepatic decompensation. The SVR by intention-to-treat was 81% with a relapse rate of 14%. The SVR by per-protocol analysis was 87% with a relapse rate of 13%. The only baseline factor associated with SVR by multifactor analysis was Child class. SVR in patients with Child class A, B, and C was 87, 77, and 67%, respectively. Eleven percent of the patients developed severe adverse events, which included sepsis (two), variceal bleeding (two), hepatocellular carcinoma (two), and hyperbilirubinemia (eight). One of the patients with sepsis died. Two patients developed relapse more than 12 weeks after stopping SMV and SOF. CONCLUSIONS: The combination of SMV and SOF achieves high rates of SVR in patients with advanced cirrhosis but is lower with worsening Child class.
Authors: Lisa I Backus; Derek B Boothroyd; Barbara R Phillips; Pamela Belperio; James Halloran; Larry A Mole Journal: Clin Gastroenterol Hepatol Date: 2011-03-11 Impact factor: 11.382
Authors: Michael Manns; Patrick Marcellin; Fred Poordad; Evaldo Stanislau Affonso de Araujo; Maria Buti; Yves Horsmans; Ewa Janczewska; Federico Villamil; Jane Scott; Monika Peeters; Oliver Lenz; Sivi Ouwerkerk-Mahadevan; Guy De La Rosa; Ronald Kalmeijer; Rekha Sinha; Maria Beumont-Mauviel Journal: Lancet Date: 2014-06-04 Impact factor: 79.321
Authors: Peter Ferenci; David Bernstein; Jacob Lalezari; Daniel Cohen; Yan Luo; Curtis Cooper; Edward Tam; Rui T Marinho; Naoky Tsai; Anders Nyberg; Terry D Box; Ziad Younes; Pedram Enayati; Sinikka Green; Yaacov Baruch; Bal Raj Bhandari; Florin Alexandru Caruntu; Thomas Sepe; Vladimir Chulanov; Ewa Janczewska; Giuliano Rizzardini; Judit Gervain; Ramon Planas; Christophe Moreno; Tarek Hassanein; Wangang Xie; Martin King; Thomas Podsadecki; K Rajender Reddy Journal: N Engl J Med Date: 2014-05-04 Impact factor: 91.245
Authors: Jose A Carrión; Eva Martínez-Bauer; Gonzalo Crespo; Santseharay Ramírez; Sofia Pérez-del-Pulgar; Juan Carlos García-Valdecasas; Miquel Navasa; Xavier Forns Journal: J Hepatol Date: 2008-12-29 Impact factor: 25.083
Authors: Eric Lawitz; Alessandra Mangia; David Wyles; Maribel Rodriguez-Torres; Tarek Hassanein; Stuart C Gordon; Michael Schultz; Mitchell N Davis; Zeid Kayali; K Rajender Reddy; Ira M Jacobson; Kris V Kowdley; Lisa Nyberg; G Mani Subramanian; Robert H Hyland; Sarah Arterburn; Deyuan Jiang; John McNally; Diana Brainard; William T Symonds; John G McHutchison; Aasim M Sheikh; Zobair Younossi; Edward J Gane Journal: N Engl J Med Date: 2013-04-23 Impact factor: 91.245
Authors: Ira M Jacobson; Stuart C Gordon; Kris V Kowdley; Eric M Yoshida; Maribel Rodriguez-Torres; Mark S Sulkowski; Mitchell L Shiffman; Eric Lawitz; Gregory Everson; Michael Bennett; Eugene Schiff; M Tarek Al-Assi; G Mani Subramanian; Di An; Ming Lin; John McNally; Diana Brainard; William T Symonds; John G McHutchison; Keyur Patel; Jordan Feld; Stephen Pianko; David R Nelson Journal: N Engl J Med Date: 2013-04-23 Impact factor: 91.245
Authors: Stefan Zeuzem; Ira M Jacobson; Tolga Baykal; Rui T Marinho; Fred Poordad; Marc Bourlière; Mark S Sulkowski; Heiner Wedemeyer; Edward Tam; Paul Desmond; Donald M Jensen; Adrian M Di Bisceglie; Peter Varunok; Tarek Hassanein; Junyuan Xiong; Tami Pilot-Matias; Barbara DaSilva-Tillmann; Lois Larsen; Thomas Podsadecki; Barry Bernstein Journal: N Engl J Med Date: 2014-04-10 Impact factor: 91.245
Authors: Adriaan J van der Meer; Bart J Veldt; Jordan J Feld; Heiner Wedemeyer; Jean-François Dufour; Frank Lammert; Andres Duarte-Rojo; E Jenny Heathcote; Michael P Manns; Lorenz Kuske; Stefan Zeuzem; W Peter Hofmann; Robert J de Knegt; Bettina E Hansen; Harry L A Janssen Journal: JAMA Date: 2012-12-26 Impact factor: 56.272
Authors: Eric Lawitz; Mark S Sulkowski; Reem Ghalib; Maribel Rodriguez-Torres; Zobair M Younossi; Ana Corregidor; Edwin DeJesus; Brian Pearlman; Mordechai Rabinovitz; Norman Gitlin; Joseph K Lim; Paul J Pockros; John D Scott; Bart Fevery; Tom Lambrecht; Sivi Ouwerkerk-Mahadevan; Katleen Callewaert; William T Symonds; Gaston Picchio; Karen L Lindsay; Maria Beumont; Ira M Jacobson Journal: Lancet Date: 2014-07-28 Impact factor: 79.321
Authors: Nezam Afdhal; K Rajender Reddy; David R Nelson; Eric Lawitz; Stuart C Gordon; Eugene Schiff; Ronald Nahass; Reem Ghalib; Norman Gitlin; Robert Herring; Jacob Lalezari; Ziad H Younes; Paul J Pockros; Adrian M Di Bisceglie; Sanjeev Arora; G Mani Subramanian; Yanni Zhu; Hadas Dvory-Sobol; Jenny C Yang; Phillip S Pang; William T Symonds; John G McHutchison; Andrew J Muir; Mark Sulkowski; Paul Kwo Journal: N Engl J Med Date: 2014-04-11 Impact factor: 91.245
Authors: Anjana A Pillai; Joel Wedd; J P Norvell; Samir Parekh; Nicole Cheng; Nikita Young; James R Spivey; Ryan Ford Journal: Am J Gastroenterol Date: 2016-02-02 Impact factor: 10.864
Authors: Fabien Zoulim; T Jake Liang; Alexander L Gerbes; Alessio Aghemo; Sylvie Deuffic-Burban; Geoffrey Dusheiko; Michael W Fried; Stanislas Pol; Jürgen Kurt Rockstroh; Norah A Terrault; Stefan Wiktor Journal: Gut Date: 2015-11 Impact factor: 23.059