F Rodriguez-Frias1, L Nieto-Aponte2, J Gregori3, D Garcia-Cehic4, R Casillas2, D Tabernero5, M Homs6, M Blasi6, M Vila6, Q Chen7, V Vargas8, Ll Castells8, Ll Viladomiu9, J Genesca8, B Minguez8, S Augustin8, M Riveiro-Barciela8, J Carbonell9, C Perales4, M E Soria4, M Asensio6, M Llorens7, L Ordeig7, C Godoy6, M Buti8, R Esteban8, T Pumarola10, J I Esteban8, J Quer11. 1. Liver Pathology Unit, Department of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain; Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain; Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: frarodri@vhebron.net. 2. Liver Pathology Unit, Department of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain; Clinical Microbiology Department, HUVH, Barcelona, Spain. 3. Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain; Roche Diagnostics SL, Sant Cugat del Vall_es, Barcelona, Spain; Liver Unit, Malalties Hepatiques, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-HUVH), Barcelona, Spain. 4. Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Malalties Hepatiques, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-HUVH), Barcelona, Spain. 5. Liver Pathology Unit, Department of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain; Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain. 6. Liver Pathology Unit, Department of Biochemistry and Microbiology, Hospital Universitari Vall d'Hebron (HUVH), Barcelona, Spain. 7. Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain. 8. Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain; Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Liver Unit, Malalties Hepatiques, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-HUVH), Barcelona, Spain. 9. Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Liver Unit, Malalties Hepatiques, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-HUVH), Barcelona, Spain. 10. Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Clinical Microbiology Department, HUVH, Barcelona, Spain. 11. Centro de Investigacion Biomedica en Red (CIBER) de Enfermedades Hepaticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, Madrid, Spain; Universitat Autonoma de Barcelona, Bellaterra, Barcelona, Spain; Liver Unit, Malalties Hepatiques, Internal Medicine Department, Vall d'Hebron Institut Recerca (VHIR)-HUVH), Barcelona, Spain. Electronic address: josep.quer@vhir.org.
Abstract
OBJECTIVES: This study aimed to characterize the chronically infected general hepatitis C virus (HCV) population in Barcelona using a highly sensitive subtyping method that can identify the 67 recognized HCV subtypes and diagnose mixed infection by various genotypes/subtypes in a single individual. The resulting information has implications for selecting optimal direct-acting antiviral (DAA) treatment for each patient and establishing public healthcare policies in our setting. METHODS: Consecutive HCV patients (treatment-naïve or interferon-based failures) attending Vall d'Hebron Hospital outpatient clinics from February 2015 to May 2016 (N=1473) were included in the study. Patient samples were characterized using HCV subtyping by next-generation ultra-deep pyrosequencing. RESULTS: The following genotypes (G) were found: G1 (1126/1473 (76.4%)), G4 (145/1473 (9.8%)), G3 (135/1473 (9.2%)), G2 (51/1473 (3.5%)), and G5 (1/1473 (0.1%)). Twenty-two subtypes were seen: 1b (790/1473 (53.6%)), 1a (332/1473 (22.5%)), 3a (133/1473 (9.0%)), 4d (105/1473 (7.1%)), 4a (29/1473 (2.0%)), and 2c (25/1473 (1.7%)), with 16 low-prevalence subtypes accounting for the remaining 3.0% (44/1473). There was a worrisome 1.0% (15/1473) of mixed infections. G2 (51/1473 (3.5%)) showed a high level of heterogeneity. Analyses by age groups showed a predominance of G1b over G1a (428/506 (84.6%) vs. 24/506 (4.7%)) in patients born before 1950 (N=506/1473), and similar percentages of these subtypes in those born between 1951 and 1975 (N=834/1473) (315/834, 37.8% vs. 266/834, 31.9%) and after 1976 (N=133/1473) (47/133, 35.3% vs. 42/133, 31.6%). CONCLUSIONS: Subtype distribution showed a higher level of heterogeneity than was expected, particularly for G2. Prevalence of mixed infections was around 1%. HCV subtype distribution related to patient age group suggested that patients born from 1936 to 1975 in our setting should undergo screening for the infection. Next-generation sequencing enabled better classification of candidates for DAA-based treatment.
OBJECTIVES: This study aimed to characterize the chronically infected general hepatitis C virus (HCV) population in Barcelona using a highly sensitive subtyping method that can identify the 67 recognized HCV subtypes and diagnose mixed infection by various genotypes/subtypes in a single individual. The resulting information has implications for selecting optimal direct-acting antiviral (DAA) treatment for each patient and establishing public healthcare policies in our setting. METHODS: Consecutive HCV patients (treatment-naïve or interferon-based failures) attending Vall d'Hebron Hospital outpatient clinics from February 2015 to May 2016 (N=1473) were included in the study. Patient samples were characterized using HCV subtyping by next-generation ultra-deep pyrosequencing. RESULTS: The following genotypes (G) were found: G1 (1126/1473 (76.4%)), G4 (145/1473 (9.8%)), G3 (135/1473 (9.2%)), G2 (51/1473 (3.5%)), and G5 (1/1473 (0.1%)). Twenty-two subtypes were seen: 1b (790/1473 (53.6%)), 1a (332/1473 (22.5%)), 3a (133/1473 (9.0%)), 4d (105/1473 (7.1%)), 4a (29/1473 (2.0%)), and 2c (25/1473 (1.7%)), with 16 low-prevalence subtypes accounting for the remaining 3.0% (44/1473). There was a worrisome 1.0% (15/1473) of mixed infections. G2 (51/1473 (3.5%)) showed a high level of heterogeneity. Analyses by age groups showed a predominance of G1b over G1a (428/506 (84.6%) vs. 24/506 (4.7%)) in patients born before 1950 (N=506/1473), and similar percentages of these subtypes in those born between 1951 and 1975 (N=834/1473) (315/834, 37.8% vs. 266/834, 31.9%) and after 1976 (N=133/1473) (47/133, 35.3% vs. 42/133, 31.6%). CONCLUSIONS: Subtype distribution showed a higher level of heterogeneity than was expected, particularly for G2. Prevalence of mixed infections was around 1%. HCV subtype distribution related to patient age group suggested that patients born from 1936 to 1975 in our setting should undergo screening for the infection. Next-generation sequencing enabled better classification of candidates for DAA-based treatment.
Authors: María Eugenia Soria; Josep Gregori; Qian Chen; Damir García-Cehic; Meritxell Llorens; Ana I de Ávila; Nathan M Beach; Esteban Domingo; Francisco Rodríguez-Frías; María Buti; Rafael Esteban; Juan Ignacio Esteban; Josep Quer; Celia Perales Journal: BMC Infect Dis Date: 2018-09-03 Impact factor: 3.090
Authors: V Saludes; A Antuori; B Reinhardt; I Viciana; E Clavijo; L Schreiber; M Tenenbaum; F Rodriguez-Frias; J Quer; L Matas; E Martró Journal: Sci Rep Date: 2019-03-06 Impact factor: 4.379