title: Applicability of Hepatitis C Virus RNA Viral Load Thresholds for 8-Week Treatments in Patients With Chronic Hepatitis C Virus Genotype 1 Infection.
abstract: Interferon-free treatment of chronic hepatitis C virus (HCV) genotype 1 infection may be shortened to 8 weeks in treatment-naive, noncirrhotic patients with baseline HCV RNA levels of <4 or <6 million (M) IU/mL based on post-hoc analyses of phase 3 trial data. The applicability of these viral load thresholds in clinical practice is unknown.
  
  
  
  Pretreatment and on-treatment serum samples (n = 740) from patients with HCV genotype 1 infection were included for HCV RNA analysis with 2 widely used assays, Cobas AmpliPrep/CobasTaqMan (CAP/CTM) and Abbott RealTime HCV (ART) assays.
  
  
  
  HCV RNA levels were significantly higher with CAP/CTM than with ART (overall difference, +0.11 log10 IU/mL; P < .001). In treatment-naive, noncirrhotic patients, discordance rates around the clinical cutoffs at 4M and 6M IU/mL were 23% and 18%, respectively. The mean differences between assays in discordant samples were 0.38 (4M) and 0.41 (6M) log10 IU/mL, respectively. Overall, 87% and 95% of treatment-naive, noncirrhotic patients, respectively, had baseline HCV RNA levels below 4M and 6M IU/mL with ART. These rates were significantly higher than those measured with CAP/CTM (64% and 78%, respectively; P < .001). Finally, discordance rates around the proposed thresholds in 2 consecutive samples of the same patient were in the range of 1%-2% for ART and 13%-17% for CAP/CTM.
  
  
  
  Selection of patients for 8-week regimens on the basis of a single HCV RNA determination may not be reliable because viral load levels around the proposed clinical thresholds show significant interassay and intrapatient variability.
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt.
authors.forename: Johannes
authors.initials: J
authors.lastname: Vermehren
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Maasoumy
authors.affiliation: Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Ontario, Canada.|Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, The Netherlands.
authors.forename: Raoel
authors.initials: R
authors.lastname: Maan
authors.affiliation: Abbott Diagnostics, Abbott Park, Illinois.
authors.forename: Gavin
authors.initials: G
authors.lastname: Cloherty
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt.
authors.forename: Caterina
authors.initials: C
authors.lastname: Berkowski
authors.affiliation: Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Ontario, Canada.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Feld
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Cornberg
authors.affiliation: National Reference Center for Viral Hepatitis B, C and D, Hôpital Henri Mondor, Université Paris-Est.|INSERM U955, Créteil, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.affiliation: Medizinische Klinik 1, Universitätsklinikum Frankfurt.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
mesh_terms: D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D021141:Nucleic Acid Amplification Techniques / Q000379:methods / Q000592:standards*; D012367:RNA, Viral / Q000097:blood*; D015203:Reproducibility of Results; D019562:Viral Load / Q000379:methods / Q000592:standards*
chemical_list: D012367:RNA, Viral
keywords: Abbott RealTime HCV; Cobas AmpliPrep/Cobas TaqMan; HCV RNA assay; baseline viral load; hepatitis C virus