BACKGROUND: The ability to predict the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on the reduction in hepatitis C virus (HCV) RNA levels at 4 weeks after starting the therapy and amino acid substitutions in HCV was to be confirmed. METHODS: We measured the reduction in HCV RNA levels at 4 weeks after starting the combination therapy, as well as examining amino acid substitutions at residue 70 in the HCV core and within the interferon sensitivity-determining region (ISDR) of HCV non-structural protein 5A (NS5A), for 101 patients infected with HCV genotype 1b. The ability of these factors to predict a sustained virologic response (SVR) was analyzed. RESULTS: When a 3 log(10) reduction in HCV RNA levels at 4 weeks after starting therapy was set as the cut-off value, an SVR was achieved in 37 of the 46 patients (80.4%) with a ≥3 log(10) decrease and in 4 of the 55 patients (7.3%) with a <3 log(10) decrease. All 4 patients who achieved an SVR despite a <3 log(10) reduction in HCV RNA levels at 4 weeks had an arginine at residue 70 in the HCV core and a non-wild-type sequence for the ISDR of HCV NS5A. CONCLUSION: A ≥3 log(10) reduction in HCV RNA levels at 4 weeks after starting therapy indicates that a patient has a high likelihood of achieving an SVR as a final outcome. Additional information on the amino acid substitutions at residue 70 in the HCV core and within NS5A-ISDR will further increase the ability to predict a clinical response.
BACKGROUND: The ability to predict the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on the reduction in hepatitis C virus (HCV) RNA levels at 4 weeks after starting the therapy and amino acid substitutions in HCV was to be confirmed. METHODS: We measured the reduction in HCV RNA levels at 4 weeks after starting the combination therapy, as well as examining amino acid substitutions at residue 70 in the HCV core and within the interferon sensitivity-determining region (ISDR) of HCV non-structural protein 5A (NS5A), for 101 patients infected with HCV genotype 1b. The ability of these factors to predict a sustained virologic response (SVR) was analyzed. RESULTS: When a 3 log(10) reduction in HCV RNA levels at 4 weeks after starting therapy was set as the cut-off value, an SVR was achieved in 37 of the 46 patients (80.4%) with a ≥3 log(10) decrease and in 4 of the 55 patients (7.3%) with a <3 log(10) decrease. All 4 patients who achieved an SVR despite a <3 log(10) reduction in HCV RNA levels at 4 weeks had an arginine at residue 70 in the HCV core and a non-wild-type sequence for the ISDR of HCV NS5A. CONCLUSION: A ≥3 log(10) reduction in HCV RNA levels at 4 weeks after starting therapy indicates that a patient has a high likelihood of achieving an SVR as a final outcome. Additional information on the amino acid substitutions at residue 70 in the HCV core and within NS5A-ISDR will further increase the ability to predict a clinical response.
Authors: P Deltenre; V Canva; M El Nady; C François; S Castelain; S Dharancy; A Louvet; L Bocket; M Lazrek; A Hollebecque; F Wartel; J Henrion; G Duverlie; P Mathurin Journal: J Viral Hepat Date: 2009-05-08 Impact factor: 3.728
Authors: N Kato; M Hijikata; Y Ootsuyama; M Nakagawa; S Ohkoshi; T Sugimura; K Shimotohno Journal: Proc Natl Acad Sci U S A Date: 1990-12 Impact factor: 11.205
Authors: Peter Ferenci; Hermann Laferl; Thomas-Matthias Scherzer; Michael Gschwantler; Andreas Maieron; Harald Brunner; Rudolf Stauber; Martin Bischof; Bernhard Bauer; Christian Datz; Karin Löschenberger; Elisabeth Formann; Katharina Staufer; Petra Steindl-Munda Journal: Gastroenterology Date: 2008-05-27 Impact factor: 22.682
Authors: P Muñoz de Rueda; J Casado; R Patón; D Quintero; A Palacios; A Gila; R Quiles; J León; A Ruiz-Extremera; J Salmerón Journal: J Virol Date: 2008-04-30 Impact factor: 5.103