Page 32 - The Flying Publisher Guide to Hepatitis C Treatment

32 | Hepatitis C Treatment

Viral kinetics: methodology
Measuring VL at baseline, as well as early after treatment
initiation may help to predict response and determine the
optimal length of therapy. As shown in chapter 1, in order to
maximize treatment effectiveness, while minimizing toxicity,
the optimal duration of PegIFN/RBV therapy is determined by
viral genotype, with additional guidance provided by the on-
treatment response (RVR being an earlier predictor of treatment
success and EVR an accurate predictor of treatment failure).

Viral load monitoring
For HCV RNA measurement, different standardized
quantification assays, based on signal amplification [branched
DNA(bDNA) assay] and target amplification [reverse-
transcription PCR (RT-PCR)] with different sensitivities are
commercially available. The development of a World Health
Organization HCV international unit (IU) standard has
contributed to a better accuracy and comparability of results
obtained by different assays. However, since standardization to
IU and the calibration of assay sensitivity are based on genotype
1a (deLeuw 2011), relative quantification results may vary
among assays. Using the WHO international standard, a VL of 2
millions copies/mL (the cut-off value predictive for therapeutic
success in early clinical trials with IFN) was found to correspond
to 800 000 IU/mL. Currently a cut-off of 400 000-800 000 IU/ml
separate low from high VL. Further studies have found that
patients with low baseline HCV RNA levels have a 15-39% better
response rate, a finding that is consistent across trials using
different formulations and dosages of IFN (Strader 2004).

Real-time PCR tests
Real-time PCR tests are faster and more cost-effective methods
that detect very low VL (10-15 IU/ml) (Vermehren 2008). Real-
time PCR can accurately quantify HCV RNA levels over a linear
range exceeding 6 logs (10 IU/mL to 100 million IU/mL) (Table