Wednesday, April 25, 2012

Virus factors

HCV genotype, pretreatment HCV RNA level (viral load-VL) and
the evolution of viral quasispecies (cluster of variant viruses that
arise from mutations over time in viral population) are strong
independent predictors of SVR to SoC therapy, as well as to
triple combination therapy with protease inhibitors.
– HCV Genotype is a major predictor of treatment response.
HCV genotypes can be ranked, in a decreasing order of
susceptibility to IFN-based treatment, as follows: genotypes
2, 3, 4 and 1. Furthermore, subtype 1b rather than 1a and
subtype 2b rather than 2a are likely to respond poorer to
IFN-based therapy. Permanent viral eradication (SVR) can
be achieved in up to 80% of individuals infected with
‘favorable’ or “easy-to-treat” HCV genotypes (G2/3), but
only in approximately 40% of those infected with
‘unfavorable’ or “difficult-to-treat” HCV genotypes
(G1/4).
– High baseline VL (with a cutoff value of 400000 IU/mL)
influences negatively the response rate in patients infected
with HCV G1 (41% versus 56%), but not significantly in those
with HCV G 2/ 3 (74% versus 81%).
– Higher viral quasispecies complexity at baseline has been
observed in nonresponders compared with sustained
18 | Hepatitis C Treatment
virological responders. Greater sequence heterogeneity
generates diverse quasispecies, thereby providing a
reservoir of mutations that enable virus-escape from
antiviral therapy (Fan 2009).

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