OBJECTIVETo review the updated research on direct antiviral agents (DAAs)-including regimens for hepatitis C virus (HCV), and focus on "difficult-to-treat" HCV-infected patients.

DATA SOURCESThe literature concerning DAAs and hepatitis C cited in this review was collected from PubMed and Google Scholar databases published in English up to July 2013.

STUDY SELECTIONData from published articles regarding HCV and DAAs in clinical trials and in clinical use were identified and reviewed.

RESULTSIt was recognized that some "difficult-to-treat" patients would still exist, even though stronger treatments using such as DAAs, including telaprevir and boceprevir, which lead to higher sustained virological response rates, are available. Such patients include those with advanced fibrosis/cirrhosis, elderly persons, children, HCV-human immunodeficiency virus co-infected patients, HCV-infected recipients, and so on.

CONCLUSIONSCertain "difficult-to-treat" patients would still exist, even though stronger treatment is available. Although evidence from clinical trials is still lacking, interferon-sparing regimens could have stronger effects for eradicating HCV in such cases.