Published online Sep 27, 2018. doi: 10.4254/wjh.v10.i9.595
Peer-review started: March 30, 2018
First decision: May 11, 2018
Revised: May 25, 2018
Accepted: June 30, 2018
Article in press: June 30, 2018
Published online: September 27, 2018
Processing time: 181 Days and 14.5 Hours
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)-αand 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.
Core tip: Inability to reach sustained virological response (SVR) and cirrhosis are independent prognostic factors for developing hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) patients from the interferon (IFN) era. DAAs offer significantly better SVR rates. The first data regarding HCC occurrence after direct antiviral agent (DAA) treatment are similar to the data from patients who achieved SVR under IFN treatment. Some reports on early HCC occurrence or recurrence after DAA treatment are probably due to selection bias, as they were not reproduced in large comparative studies. DAAs can eradicate HCV, but they cannot terminate HCV-induced premalignant processes once triggered.