The expanded classification of hepatitis C virus (HCV) genome into various genotypes and numerous subtypes significantly correlates to therapeutic outcomes of interferon-free direct-acting antivirals (DAAs) in HCV treated patients. In particular, genotypes 3 and 4 are still harder to treat, and higher sustained virologic response (SVR) rates are not achieved in some difficult-to-treat specific populations (i.e., HCV subtype 1a patients, compensated and decompensated cirrhotic patients, HCV/HIV co-infection, and prior treatment failure with pegylated interferon plus ribavirin and first-generation protease inhibitor based therapeutic regimens). Furthermore, the pre-existing and treatment-emergent resistance associated substitutions (RAS) at specific amino acid positions within the viral quasispecies may increase the chances of viral breakthrough (HCV RNA remains lower limit of quantification, but increased to 100 IU/mL or 1.log10 during DAAs therapy), viral relapse (undetectable viral load at the end of treatment but positive within the follow-up of 6 months), and discontinuation of therapy in treated individuals. Although the clinical importance of RAS is not entirely elucidated, it is believed that such substitutions decrease the therapeutic efficacy of DAAs in treated individuals. Similarly, the emergence of multiclass hepatitis C virus resistance to interferon-free DAAs failure in real-world experiences demands eagerly tailored second-line anti-hepatitis C therapies. This book chapter comprehensively overviews the clinical correlation of HCV genotypes, viral quasispecies and harboring RAS to treatment outcomes of revolutionary interferon-free DAAs in hepatitis C-treated patients.
Part of the book: Genotyping