Tuesday, February 26, 2019

Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification

Open Forum Infectious Diseases
Published: 22 February 2019 

Accepted Manuscript
Identification of 19 Novel Hepatitis C Virus Subtypes-Further Expanding HCV Classification 
Charlotte Hedskog1, Bandita Parhy1, Silvia Chang1, Stefan Zeuzem2, Christophe Moreno3, Stephen D.Shafran4, Sergio M. Borgia5, Tarik Asselah6, Laurent Alric7, Armand Abergel8, Jyh-Jou Chen9, Jane Collier10,Dharmesh Kapoor11, Robert H. Hyland1, Peter Simmonds12, Hongmei Mo1, Evguenia S. Svarovskaia

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Abstract
Background
The hepatitis C virus (HCV) is currently classified into 8 genotypes and 86 subtypes. The objective of this study was to characterize novel HCV subtypes and to investigate the impact of subtypes on treatment outcome. 

Methods
Full genome sequencing was performed on HCV plasma samples with <85% sequence homology of NS3, NS5A and/or NS5B to HCV genotype (GT) 1 to 8 reference strains.

Results
14,653 patients with GT1 to 6 HCV infection were enrolled in clinical studies of sofosbuvir-based regimens. For the majority of the patients, a specific subtype could be assigned based on a close genetic relationship to previously described subtypes. However for 19 patients, novel subtypes were identified with <85% homology compared to previously described subtypes. These novel subtypes had the following genotypes; 9 in GT2, 5 in GT4, 2 in GT6 and one each in GT1, GT3 and GT5. Despite presence of polymorphisms at resistance-associated substitutions (RAS) positions, 18 of the 19 patients treated with sofosbuvir-containing therapy achieved SVR12. 

Conclusions
Nineteen novel HCV subtypes were identified, suggesting an even greater genetic diversity of HCV subtypes than previously recognized. 

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