Baseline HCV RNA of 400,000 Best Predicts SVR and Relapse Rates in
Patients Treated with Pegasys plus Ribavirin
HCV RNA (viral load) has been recognized as an important predictor for
treatment outcomes in patients with chronic HCV. Increasingly, determination
of the viral load also is becoming relevant to the duration of treatment.
Until recently, most studies have used an HCV RNA cut-off of 800,000 IU/mL
to define high and low pre-treatment viral load. However, recent
observations suggest that this cut-off may not be sensitive enough to guide
individualized treatment decision-making.
As reported at the 57th AASLD annual meeting taking place this week in
Boston, researchers identified a baseline HCV RNA cut-off level that can
predict most effectively sustained virological response rates (SVR) as well
as relapse rates.
The study group consisted of 455 HCV genotype 1 patients at 13 German
medical centers* who received pegylated interferon alfa-2a (Pegasys) 180
mcg/week plus ribavirin 800 mg/day for either 48 (n=230) or 72 (n=225) weeks
in a Phase III randomized clinical trial.
The baseline level that most effectively
differentiated between a high and low probability of SVR in the total
population was 400,000 IU/mL.
This cut-off had a sensitivity of 0.43 and a
specificity of 0.78.
The SVR rate in patients with HCV viral load ?
400,000 IU/mL was 70%, compared to 46% in patients with baseline viral load
> 400,000 IU/mL (P < 0.0001).
In contrast, using the 800,000 IU/mL viral load
cut-off, SVRs were 58% and 45%, respectively, in patients with low and high
viral load (P = 0.007).
Analyzing patients treated for 72 weeks, the
400,000 IU/mL viral load cut-off was predictive of SVR (66% vs 48% in low vs
high viral load; P = 0.01), but the 800,000 IU/mL cut-off was not (57% vs
48%, respectively; P = 0.2).In predicting virological relapse, the 400,000
IU/mL pre-treatment viral load cut-off proved superior to the 800,000 IU/mL
In the 72-week
treatment group, virological relapse rates were statistically highly
different when comparing baseline viral load ? 400,000 vs > 400,000 IU/mL
(6% vs 29% in low vs high viral load; P = 0.001).
These clear differences disappeared when a
baseline cut-off of 800,000 IU/mL was used (17% vs 29%, respectively; P =
In the 48-week treatment group, relapse rates
with respect to low vs high viral load cut-off of 400,000 or 800,000 IU/mL
were 15% vs 36% (P = 0.004) or 24% vs 36% (P = 0.08), respectively.
In conclusion, the researchers wrote, "This analysis shows that a baseline
HCV RNA level of approximately 400,000 IU/mL has the highest statistical
power to predict SVR as well as relapse rates in HCV type 1-infected
patients treated for either 48 or 72 weeks with peginterferon-alpha-2a plus
"Use of this cut-off point will allow treatment optimization in genotype 1
patients," they added.
*Charite, Berlin, Germany, Universitätskliniken des Saarlandes, Homburg,
Germany; Christian-Albrecht-Universität, Kiel, Germany, Heinrich-Heine-Universität,
Düsseldorf, Germany; Universitätsklinik Eppendorf, Hamburg, Germany;
Universität zu Köln, Köln, Germany; Medizinische Universitätsklinik,
Freiburg, Germany; Klinikum Grosshadern, München, Germany; Medizinische
Universitätsklinik, Bochum, Germany; Universitätsklinik Heidelberg,
Heidelberg, Germany; Klinikum der Universität Würzburg, Würzburg, Germany;
Medizinische Einrichtung der Rh. Fr. Wilhelms Universität Bonn, Bonn,
Germany; Roche Grenzach, Grenzach, Germany.
T Berg, M von Wagner, H Hinrichsen, and others. Definition of a
pre-treatment viral load cut-off for an optimized prediction of treatment
outcome in patients with genotype 1 infection receiving either 48 or 72
weeks of peginterferon alfa-2a plus ribavirin. 57th AASLD. October 27-31,
2006. Boston, MA. Abstract 350.