Published online Aug 7, 2016. doi: 10.3748/wjg.v22.i29.6573
Peer-review started: March 22, 2016
First decision: May 12, 2016
Revised: May 25, 2016
Accepted: June 15, 2016
Article in press: June 15, 2016
Published online: August 7, 2016
The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.
Core tip: The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response as compared with the standard treatment of peginterferon/ribavirin. The presence of resistance-associated variants (RAVs) can reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs . As well as the presence of RAVs, virological failure is generally associated with other factors related with a poor response. Nonetheless, therapeutic failure can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the RAVs remains to be determined.