Summary Background: Novel, directly acting antiviral agents, also named "specifically targeted antiviral therapy for hepatitis C" (STAT-C) compounds, are currently under development in order to improve treatment opportunities of chronic hepatitis C virus (HCV) infection.
Aim: To review the potential of STAT-C agents which are currently under clinical development with a focus on agents that target HCV proteins.
Methods: Studies evaluating STAT-C compounds were identified by systematic literature search using PubMed as well as databases of abstracts presented in English at recent liver and gastroenterology congresses.
Results: Numerous directly acting antiviral agents are currently under clinical phase I-III evaluation. Final results of phase II clinical trials evaluating the most advanced compounds telaprevir and boceprevir indicate that the addition of these NS3/4A protease inhibitors to pegylated interferon-alfa and ribavirin strongly improves the chance to achieve a SVR in treatment-naive HCV genotype 1 patient as well as in prior non-responders and relapsers to standard therapy. Monotherapy with directly acting antivirals is not suitable since it frequently results in the selection of resistant quasispecies and viral breakthrough. NS5B polymerase inhibitors in general have a lower antiviral efficacy than protease inhibitors and their potency to improve SVR rates remains to be established.
Conclusion: STAT-C compounds in addition to pegylated interferon-alfa and ribavirin are capable to improve SVR rates at least in HCV genotype 1 patients and will therefore be included in future treatment recommendations and guidelines. Future research needs to evaluate whether a SVR can be achieved by combination therapies of STAT-C compounds in interferon-free regimens.