Review article: specifically targeted anti-viral therapy for hepatitis C - a new era in therapy

Background Novel, directly acting anti-viral agents, also named 'specifically targeted anti-viral therapy for hepatitis C' (STAT-C) compounds, are currently under development. 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 anti-viral 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 nonresponders and relapsers to standard therapy. Monotherapy with directly acting anti-virals is not suitable. NS5B polymerase inhibitors in general have a lower anti-viral efficacy than protease inhibitors. Conclusions STAT-C compounds in addition to pegylated interferon-alfa and ribavirin can improve SVR rates at least in HCV genotype 1 patients. Future research needs to evaluate whether a SVR can be achieved by combination therapies of STAT-C compounds in interferon-free regimens. Aliment Pharmacol Ther 2010; 32: 14-28