Hepatitis C virus (HCV) chronic infection induces liver fibrosis and cirrhosis but is also responsible for a significant portion of hepatocellular carcinoma (HCC) occurrence. Since it was recognized as a causative factor of chronic hepatitis, there have been multiple efforts towards viral eradication, leading to the first-generation HCV treatment that was based on interferon (IFN)-α and its analogs, mainly PEGylated interferon-α (PEG IFNα). Sustained virological response (SVR), defined as the absence of detectable RNA of HCV in blood serum for at least 24 wk after discontinuing the treatment, was accepted as a marker of viral clearance and was achieved in approximately one-half of patients treated with PEG IFNα regimens. Further research on the molecular biology of HCV gave rise to a new generation of drugs, the so-called direct antiviral agents (DAAs). DAA regimens, as implied by their name, interfere with the HCV genome or its products and have high SVR rates, over 90%, after just 12 wk of per os treatment. Although there are no questions about their efficacy or their universality, as they lack the contraindication for advanced liver disease that marks PEG IFNα, some reports of undesired oncologic outcomes after DAA treatment raised suspicions about possible interference of this treatment in HCC development. The purpose of the present review is to investigate the validity of these concerns based on recent clinical studies, summarize the mechanisms of action of DAAs and survey the updated data on HCV-induced liver carcinogenesis.
Keywords: Direct antiviral agents; Hepatitis C virus infection; Hepatitis C virus-induced cancer sequence; Hepatocellular carcinoma; Liver carcinogenesis; Sustained virological response; advanced fibrosis.