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.

Results

 

	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 cut-off.
	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 = 0.11).
	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.

Conclusion

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 ribavirin."

"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.