Page 16 - The Flying Publisher Guide to Hepatitis C Treatment

16 | Hepatitis C Treatment

2010) suggests that PegIFN alfa-2a may be associated with an
increased benefit in terms of SVR compared to PegIFN alfa-2b,
although the largest head-to-head trial (IDEAL study) failed to
find a significant difference in SVR rates between the two PegIFN
formulations (McHutchison 2009). Nevertheless, the two
products seem to be comparable in terms of adverse effects (AEs)
leading to treatment discontinuation.
As long as SVR is only a surrogate marker of clinical outcomes
(liver failure, HCC and mortality) and the data on the long-term
AEs are limited, both regimens seems to be equally effective in
the clinical practice.
It is important to mention that HCV has notable properties by
which it can inhibit the actions of IFNs. The HCV protease
NS3/4A blocks important proteins and enzymes within the cells
(such as IRF3, a key transcriptional regulator of the IFN
response, and retinoid-inducible gene 1- RIG1, a growth
regulator), leading to a reduction in the expression of IFN-
signaling genes (Bode 2008).
Ribavirin (RBV) has both antiviral and immunomodulatory
actions. Although RBV monotherapy has little influence against
HCV, in combination with interferon it improves dramatically
the response rates. Being a guanosine analog, RBV acts by direct
inhibition of nucleic acid elongation and of enzymes important
in viral replication, such as inosine monophosphate
dehydrogenase (IMPDH), as well as by induction of lethal
mutagenesis during the viral life-cycle. Although the specific
mechanism has not yet been completely elucidated, there is
increasing evidence of RBV acting as a true antiviral agent and
thus having a critical role in the suppression of viral replication.
RBV amplifies the effect of IFN, generating a significant decrease
in the relapse rate (Manns 2001, Fried 2002).
Adding RBV to PegIFNs was recommended by consensus in
Europe in 1999 and in the United States in 2002. Subsequently, it
has been shown that weight–dosed RBV is more effective in
acquiring a high rate of therapeutic success. In today’s regimens,
RBV is administered according to patient’s weight: 1000 mg/day