Johannes Vermehren1, Benjamin Maasoumy2, Raoel Maan3,4, Gavin Cloherty5, Caterina Berkowski1, Jordan J Feld3, Markus Cornberg2, Jean-Michel Pawlotsky6,7, Stefan Zeuzem1, Michael P Manns2, Christoph Sarrazin1, Heiner Wedemeyer2. 1. Medizinische Klinik 1, Universitätsklinikum Frankfurt. 2. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany. 3. Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, University of Toronto, Ontario, Canada. 4. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, The Netherlands. 5. Abbott Diagnostics, Abbott Park, Illinois. 6. National Reference Center for Viral Hepatitis B, C and D, Hôpital Henri Mondor, Université Paris-Est. 7. INSERM U955, Créteil, France.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: 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: Benjamin Maasoumy; Birgit Bremer; Patrick Lehmann; Ed G Marins; Véronique Michel-Treil; Christian O Simon; Merlin Njoya; Markus Cornberg; Ellen Paxinos; Michael P Manns; Johannes Vermehren; Christoph Sarrazin; Ji Yeon Sohn; Yunjung Cho; Heiner Wedemeyer Journal: Therap Adv Gastroenterol Date: 2017-08-07 Impact factor: 4.409
Authors: Johannes Vermehren; Evelyn Stelzl; Benjamin Maasoumy; Veronique Michel-Treil; Caterina Berkowski; Ed G Marins; Ellen E Paxinos; Enrique Marino; Heiner Wedemeyer; Christoph Sarrazin; Harald H Kessler Journal: J Clin Microbiol Date: 2017-01-25 Impact factor: 5.948
Authors: Nicholas J Burstow; Zameer Mohamed; Asmaa I Gomaa; Mark W Sonderup; Nicola A Cook; Imam Waked; C Wendy Spearman; Simon D Taylor-Robinson Journal: Int J Gen Med Date: 2017-02-17