Current Landscape of HCV Therapeutics

During the last decade, the advent and approval of almost a dozen all-oral interferon-free direct-acting antivirals (IFN-free DAAs) to cure hepatitis C-infected general and harder-to-treat populations have entirely changed the treatment paradigms against this “silent epidemic”. The clinical trials of generic IFN-free DAAs, while achieving 95% to 100% sustained virologic response rates (SVRs) in treated individuals, have proven their worth as “magic pills” in hepatitis C therapeutics. Following their real-world clinical usage data with SVR rates, more than 95% have raised the hopes to treat everyone infected with hepatitis C in near future, albeit certain barriers still need to be broken. These regimens, in combination or as a fixed-dose combination (FDC) of a single pill, are highly efficacious against all major hepatitis C genotypes and sub-genotypes. Furthermore, the regimens are well tolerable, with fewer adverse events, and with lesser chances of post-treatment viral relapse or breakthrough in treated patients. The dose algorithms are well-defined for all adult patient groups and in different pathological states of the infection and their recommendations are according to extrahepatic manifestations of hepatitis C in infected individuals. Furthermore, the clinical trials of some DAAs are underway to approve their recommendations in HCV-infected infants, children, and pregnant female patients. In this chapter, we will illustrate the most attractive pharmaco-characteristics of these novel therapeutic regimens to be considered while treating hepatitis C-infected populations. We will also elaborate on the infected subpopulations for which such regimens are not recommended and further research is extensively needed. 

Keywords: Cirrhosis, Direct-acting antivirals, Fibrosis, Hepatocellular carcinoma, HCV/HBV Co-infection, HCV/HIV Co-infection, HCV/CKD Coinfection, Harder-to-treat populations, HCV Therapeutics, Resistance-associated substitutions, Sustained virologic response, Treatment-naïve patients, Treatmentexperienced patients, Treatment-associated adverse events.