High HCV subtype heterogeneity in a chronically infected general population revealed by high-resolution hepatitis C virus subtyping

F. Rodriguez-Frias, L. Nieto-Aponte, J. Gregori, D. Garcia-Cehic, R. Casillas, D. Tabernero, M. Homs, M. Blasi, M. Vila, Q. Chen, V. Vargas, Ll Castells, Ll Viladomiu, J. Genesca, B. Minguez, S. Augustin, M. Riveiro-Barciela, J. Carbonell, C. Perales, M. E. SoriaM. Asensio, M. Llorens, L. Ordeig, C. Godoy, M. Buti, R. Esteban, T. Pumarola, J. I. Esteban, J. Quer

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Abstract

© 2017 European Society of Clinical Microbiology and Infectious Diseases 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.
Original languageEnglish
Pages (from-to)775.e1-775.e6
JournalClinical Microbiology and Infection
Volume23
Issue number10
DOIs
Publication statusPublished - 1 Oct 2017

Keywords

  • HCV
  • Hepatitis C virus
  • High-resolution HCV subtyping
  • Mixed infections
  • Prevalence
  • Subtypes

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    Rodriguez-Frias, F., Nieto-Aponte, L., Gregori, J., Garcia-Cehic, D., Casillas, R., Tabernero, D., Homs, M., Blasi, M., Vila, M., Chen, Q., Vargas, V., Castells, L., Viladomiu, L., Genesca, J., Minguez, B., Augustin, S., Riveiro-Barciela, M., Carbonell, J., Perales, C., ... Quer, J. (2017). High HCV subtype heterogeneity in a chronically infected general population revealed by high-resolution hepatitis C virus subtyping. Clinical Microbiology and Infection, 23(10), 775.e1-775.e6. https://doi.org/10.1016/j.cmi.2017.02.007