Abstract

Certain hepatitis C-infected populations are still challenging to treat in the era of all-oral interferon-free direct-acting antivirals (IFN-free DAAs), which are highly efficacious, well-tolerable, and relatively safe in treated individuals. Such difficult-to-treat patients were also challenging even to manage with pegylated interferon (PEG-IFN) plus a nucleoside analog ribavirin (RBV) once known as the “gold standard of hepatitis C care”. People infected with hepatitis C genotype 3, decompensated cirrhosis, individuals with co-infection status (e.g., HCV/HBV, HCV/HIV, HCV/CKD), hepatitis C patients with induction of hepatocellular carcinoma (HCC), previous treatment failure with PEG-IFN plus RBV or DAAs failures, and viral relapse patients with the use of one or more DAA combinations are even compromised to achieve higher SVR rates with IFN-free DAAs. Similarly, some DAAs have suboptimal clinical efficacies in harder-to-cure populations and some are contraindicated and can worsen hepatitis C-associated hepatic pathological states if administered without drug monitoring. Interestingly, DAAs in clinical trials conducted for their administration approvals demonstrated to achieve satisfactory SVRs in hepatitis Cinfected special populations. Recently, limited data from real-world cohorts depict the excellent efficacy and safety of IFN-free DAAs in real-life clinical situations, similar to clinical trials. It is still uncertain whether either viral or host factors are responsible for the trivial effectiveness of DAAs in such populations. In this chapter, we will discuss the management of harder-to-treat special populations with DAAs by exploring some real-world cohort data as well as the treatment algorithms, guidelines, and recommendations for those patients in real-world clinical settings.