Page 27 - The Flying Publisher Guide to Hepatitis C Treatment

Antiviral Therapy: The Basics
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obtain an eRVR under triple therapy containing a protease
inhibitor, are eligible for RGT and a shortened duration of
treatment (24 weeks). Failure to achieve an eRVR cannot be used
as a stopping rule; continuation of therapy leads to SVR in a
considerable number of patients.
Nonresponders and relapsers
Using on-treatment viral kinetics, the following categories of
treatment failure can be defined:
– virologic breakthrough: HCV RNA reappearance while still
on treatment
– virologic relapse: undetectable HCV RNA at the end of
therapy, but HCV RNA reappearance after completion of
therapy
– nonresponse: failure to achieve undetectable HCV RNA
throughout treatment
Further detailing of the nonresponse category have been made
based on the observation that SVR rates are significantly higher
if more than 1 log 10 reduction was registered at week 12 (Zeuzem
2011):
– null responders – patients with <2 log 10 decrease in HCV
RNA level by week 12, who never reach undetectable levels
throughout the course of treatment
– partial responders – patients with >2 log 10 decrease by
week 12, despite remaining detectable during treatment
All HCV-infected individuals who fail to respond or who relapse
have a series of pre-treatment and on-treatment fixed factors
(genotypes 1/4, advanced fibrosis, older age, race and genetic
background- risk alleles at IL28B gene (CT or particularly TT)
or/and correctable factors (patient adherence, AEs associated
with therapy) that contribute to the therapy failure (Missiha
2008). Overcoming these obstacles substantially increase the
chances for success, as will be shown in detail in chapter 3.
Moreover, failure to eradicate HCV infection does not mean that
the patient is non-responsive to therapy, as most patients