A Focus on Hepatitis C: Novel Therapeutic Regimens

Editor's Note:
Based on presentations delivered at The Liver Meeting 2015—the 66th Annual Meeting of the American Association for the Study of Liver Diseases—this is the second of a three-part series on hepatitis C and reviews novel therapeutic strategies directed against the infection. Part 1 focused on prevalence, screening methods, and access and barriers to care.
Research presented at The Liver Meeting 2015 further documented the efficacy and safety of the approved direct-acting antiviral agents (DAAs) in the treatment of hepatitis C virus (HCV) infection, as well as newly emerging combinations. Although every presentation cannot be reviewed, a few have been selected to highlight our progress in treating this infection and the challenges that remain.

Antivirals for HCV

Novel therapeutic strategies directed against HCV are based on a cocktail of DAAs that are most commonly used in fixed-dose combinations and constructed on the basis of their synergistic mechanisms of action. They are highly effective against the entire spectrum of HCV genotypes and patient populations.
The currently or soon to be available antiviral agents are outlined below and include NS3/4A protease inhibitors, which act by interrupting the HCV life cycle; NS5A inhibitors, which block the HCV replication complex and the assembly and release of HCV particles; nucleotide inhibitors, which cause HCV synthesis chain termination; and nonnucleoside inhibitors, which block HCV replication.

• Simeprevir—an oral NS3/4A protease inhibitor;
• Paritaprevir—an NS3 protease inhibitor, combined with low-dose ritonavir;
• Asunaprevir—an NS3 protease inhibitor;
• Grazoprevir (GZR)—an NS3/4A protease inhibitor;
• Ledipasvir (LDV)—an NS5A inhibitor;
• Daclatasvir (DCV)—a pangenotypic NS5A replication complex inhibitor;
• Elbasvir (EBR)—an NS5A replication complex inhibitor;
• Velpatasvir (VEL)—a pangenotypic inhibitor of the NS5A protein;
• Ombitasvir—an NS5A inhibitor;
• Sofosbuvir (SOF)—a uridine nucleotide analogue and a pangenotypic, selective inhibitor of NS5B polymerase; and
• Dasabuvir—a nonnucleoside NS5B polymerase inhibitor.

Despite ongoing concerns regarding access and affordability, these interferon-free DAAs have clearly become the therapeutic option of choice, owing to their documented efficacy, tolerability, and ease of use.
The development of ribavirin (RBV)-free single-tablet regimens of short duration that are effective in a broad range of patients with HCV promises to further simplify decision-making and to reduce the need for pretreatment testing and monitoring during therapy.^[1] For example, a shortened treatment duration, which might increase compliance and decrease costs, has been tested for easy-to-cure treatment-naive patients without cirrhosis who are infected with HCV genotype 1.
Although the choice of agent is based on HCV genotype and subtype, treatment history, and stage of fibrosis, clinicians must stay tuned to the ever-changing landscape as new agents emerge. Updated guidelines are a useful resource when selecting the optimal therapy for an HCV-infected individual.